Logo: to the web site of Uppsala University

uu.sePublications from Uppsala University
Change search
Refine search result
1234567 51 - 100 of 514
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 51.
    Bruck, Katharina
    et al.
    Amsterdam Med Ctr, European Renal Assoc European Dialysis & Transpla, Dept Med Informat, Meibergdreef 9, NL-1100 DD Amsterdam, Netherlands..
    Stel, Vianda S.
    Amsterdam Med Ctr, European Renal Assoc European Dialysis & Transpla, Dept Med Informat, Meibergdreef 9, NL-1100 DD Amsterdam, Netherlands..
    Gambaro, Giovanni
    Univ Cattolica Sacro Cuore, Columbus Gemelli Univ Hosp, Div Nephrol & Dialysis, I-00168 Rome, Italy..
    Hallan, Stein
    Norwegian Univ Sci & Technol, Fac Med, St Olavs Hosp, Dept Nephrol, N-7034 Trondheim, Norway..
    Volzke, Henry
    Univ Med Greifswald, Dept Clin Epidemiol Res, Greifswald, Germany..
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Kastarinen, Mika
    Kuopio Natl Inst Hlth & Welf, Dept Internal Med & Nephrol, Finnish Med Agcy, Helsinki, Finland..
    Guessous, Idris
    Univ Hosp Geneva, Dept Community Med Primary Care & Emergency Med, Geneva, Switzerland..
    Vinhas, Jose
    Setubal Hosp Ctr, Dept Med, Setubal, Portugal..
    Stengel, Benedicte
    INSERM, U1018, Res Ctr Epidemiol & Populat Hlth, Villejuif, France..
    Brenner, Hermann
    Heidelberg Univ, German Canc Res Ctr, Network Aging Res, Div Clin Epidemiol & Aging Res, Heidelberg, Germany..
    Chudek, Jerzy
    Med Univ Silesia, Dept Nephrol Endocrinol & Metab Dis, Med Fac, Dept Pathophysiol, Katowice, Poland..
    Romundstad, Solfrid
    Norwegian Univ Sci & Technol, Levanger Hosp, Hlth Trust Nord Trendelag, Dept Nephrol, N-7034 Trondheim, Norway..
    Tomson, Charles
    Freeman Rd Hosp, Dept Nephrol, Newcastle Upon Tyne, Tyne & Wear, England..
    Otero Gonzalez, Alfonso
    Univ Hosp Orense, Dept Nephrol, Orense, Spain..
    Bello, Aminu K.
    Univ Alberta, Dept Med, Edmonton, AB, Canada..
    Ferrieres, Jean
    Toulouse Univ, Sch Med, Rangueil Hosp, Dept Cardiol, Toulouse, France..
    Palmieri, Luigi
    Ist Super Sanita, Dept Epidemiol Cerebro & Cardiovasc Dis, Viale Regina Elena 299, I-00161 Rome, Italy..
    Browne, Gemma
    Univ Coll Cork, Dept Epidemiol & Publ Hlth, Cork, Ireland.;Mercy Univ Hosp, Cork, Ireland..
    Capuano, Vincenzo
    Mercato S Severino Hosp, Unite Operat Cardiol, Salerno, Italy.;Mercato S Severino Hosp, UTIC, Salerno, Italy..
    Van Biesen, Wim
    Ghent Univ Hosp, Dept Nephrol, Ghent, Belgium..
    Zoccali, Carmine
    CNR, Ist Fisiol Clin, Clin Epidemiol & Pathophysiol Renal Dis & Hyperte, Reggio Di Calabria, Italy..
    Gansevoort, Ron
    Univ Med Ctr Groningen, Grad Sch Med Sci, Dept Nephrol, NL-9713 AV Groningen, Netherlands..
    Navis, Gerjan
    Univ Med Ctr Groningen, Dept Internal Med, Div Nephrol, NL-9713 AV Groningen, Netherlands..
    Rothenbacher, Dietrich
    Univ Ulm, Inst Epidemiol & Med Biometry, D-89069 Ulm, Germany..
    Ferraro, Pietro Manuel
    Univ Cattolica Sacro Cuore, Columbus Gemelli Univ Hosp, Div Nephrol & Dialysis, I-00168 Rome, Italy..
    Nitsch, Dorothea
    London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London WC1, England.;UCL, London, England..
    Wanner, Christoph
    Univ Hosp Wurzburg, Dept Nephrol, Wurzburg, Germany..
    Jager, Kitty J.
    Amsterdam Med Ctr, European Renal Assoc European Dialysis & Transpla, Dept Med Informat, Meibergdreef 9, NL-1100 DD Amsterdam, Netherlands..
    Consortium, European C. K. D. Burden
    CKD Prevalence Varies across the European General Population2016In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 27, no 7, p. 2135-2147Article in journal (Refereed)
    Abstract [en]

    CKD prevalence estimation is central to CKD management and prevention planning at the population level. This study estimated CKD prevalence in the European adult general population and investigated international variation in CKD prevalence by age, sex, and presence of diabetes, hypertension, and obesity. We collected data from 19 general-population studies from 13 European countries. CKD stages 1-5 was defined as eGFR <60 ml/min per 1.73 m(2), as calculated by the CKD-Epidemiology Collaboration equation, or albuminuria >30 mg/g, and CKD stages 3-5 was defined as eGFR<60 ml/min per 1.73 m(2). CKD prevalence was age- and sex-standardized to the population of the 27 Member States of the European Union (EU27). We found considerable differences in both CKD stages 1-5 and CKD stages 3-5 prevalence across European study populations. The adjusted CKD stages 1-5 prevalence varied between 3.31% (95% confidence interval [95% CI], 3.30% to 3.33%) in Norway and 17.3% (95% Cl, 16.5% to 18.1%) in northeast Germany. The adjusted CKD stages 3-5 prevalence varied between 1.0% (95% CI, 0.7% to 1.3%) in central Italy and 5.9% (95% CI, 5.2% to 6.6%) in northeast Germany. The variation in CKD prevalence stratified by diabetes, hypertension, and obesity status followed the same pattern as the overall prevalence. In conclusion, this large-scale attempt to carefully characterize CKD prevalence in Europe identified substantial variation in CKD prevalence that appears to be due to factors other than the prevalence of diabetes, hypertension, and obesity.

  • 52.
    Bååth, Carina
    et al.
    Karlstad Univ, Fac Hlth Sci & Technol, Dept Hlth Sci, Univ Gatan 2, S-65188 Karlstad, Sweden.
    Engström, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences. Univ Uppsala Hosp, Surg & Oncol Div, Uppsala, Sweden.
    Gunningberg, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences. Univ Uppsala Hosp, Surg & Oncol Div, Uppsala, Sweden.
    Muntlin Athlin, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Univ Adelaide, Sch Nursing, Adelaide, SA, Australia.; Univ Uppsala Hosp, Dept Emergency Care, Uppsala, Sweden.
    Prevention of heel pressure ulcers among older patients - from ambulance care to hospital discharge: A multi-centre randomized controlled trial.2016In: Applied Nursing Research, ISSN 0897-1897, E-ISSN 1532-8201, Vol. 30, p. 170-175Article in journal (Refereed)
    Abstract [en]

    UNLABELLED: The aim was to investigate the effect of an early intervention, a heel suspension device boot, on the incidence of heel pressure ulcers among older patients (aged 70+).

    BACKGROUND: Pressure ulcers are a global healthcare issue; furthermore, the heel is an exposed location. Research indicates that preventive nursing interventions starting during the ambulance care and used across the acute care delivery chain are seldom used.

    METHODS: A multi-centre randomized control study design was used. Five ambulance stations, two emergency departments and 16 wards at two Swedish hospitals participated. Altogether, 183 patients were transferred by ambulance to the emergency department and were thereafter admitted to one of the participating wards.

    RESULTS: Significantly fewer patients in the intervention group (n=15 of 103; 14.6%) than the control group (n=24 of 80; 30%) developed heel pressure ulcers during their hospital stay (p=0.017).

    CONCLUSIONS: Pressure ulcer prevention should start early in the acute care delivery chain to increase patient safety.

  • 53.
    Cai, Gui-Hong
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Theorell-Haglöw, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Elmståhl, Sölve
    Lund Univ, Skane Univ Hosp, Sweden CRC, Dept Hlth Sci,Div Geriatr Med, Malmo, Sweden..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Both Weight at Age 20 and Weight Gain Have an Impact on Sleep Disturbances Later in Life: Results of the EpiHealth Study2018In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 41, no 1, article id zsx176Article in journal (Refereed)
    Abstract [en]

    Study Objectives: Obesity is often associated with impaired sleep, whereas the impact of body mass index (BMI) at younger age and previous weight gain on sleep problems remains unknown.

    Methods: The present study utilized data from the Swedish EpiHealth cohort study. A total of 15 845 participants (45-75 years) filled out an internet-based questionnaire. BMI was calculated from both measured data at study time and self-reported data at age 20 from the questionnaire.

    Results: Sleep-related symptoms were most common among obese individuals (BMI >30 kg/m(2)). An association between weight gain and sleep problems was found and those with a low BMI at age 20 were most vulnerable to weight gain when it came to risk of sleep problems. Among those who were underweight (BMI <18.5 kg/m(2)) at age 20, weight gain (kg/year) was associated with difficulties initiating sleep with an adjusted OR of 2.64 (95% CI: 1.51-4.62) after adjusting for age, sex, smoking, alcohol consumption, physical activity, education, and civil status. The corresponding adjusted OR's among those who had been normal weight (BMI 18.5-24.99) and overweight (BMI 25-29.99 kg/m(2)) at age 20 were 1.89 (1.47-2.45) and 1.02 (0.48-2.13), respectively. Also difficulties maintaining sleep and snoring were most strongly related to weight gain among those who were underweight at age 20 with decreasing odds with increasing BMI at that age.

    Conclusions: Sleep problems are related to weight gain and obesity. The impact of weight is most pronounced among those who had a low BMI when young.

  • 54.
    Cai, Gui-Hong
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Theorell-Haglöw, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Svartengren, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Elmstahl, Solve
    Lund Univ, Div Geriatr Med, Dept Hlth Sci, Sweden CRC,Skane Univ Hosp, Malmo, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Insomnia symptoms and sleep duration and their combined effects in relation to associations with obesity and central obesity2018In: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 46, p. 81-87Article in journal (Refereed)
    Abstract [en]

    Objective: Previous studies have shown that both sleep duration and insomnia have an impact on obesity and central obesity. However, studies of the joint effects of these sleep disorders are still sparse. Methods: The present study utilized data from the Swedish EpiHealth cohort study. Participants (45 - 78 y) were asked to fill out an internet-based questionnaire. Body mass index (BMI) and central obesity (calculated from waist circumference) were based on measured data. Results: A total of 18,823 participants (mean age = 60 ys) were included in this study. The reported prevalence of short (<6 h/night) and long (>9 h/night) sleep duration was 8% and 4% respectively, and insomnia symptoms was 19%. Of the study population, 16% were obese (BMI >= 30 kg/m(2)) and 40% had central obesity. There was a U-shaped association between sleep duration and obesity and central obesity, and significant associations between insomnia symptoms and obesity. When stratifying sleep duration by concurrent insomnia symptoms, there were associations (odds ratios, (95% confidence intervals)) between the combination of both short (1.48, (1.22-1.80)) and long sleep duration (1.77 (1.00 - 3.16)) with insomnia symptoms and obesity and central obesity (1.36 (1.16-1.61) and 2.44 (1.41-3.24) respectively). However, there was no significant association between insomnia symptoms and obesity or central obesity in participants with normal sleep duration. For central obesity there was an association with long sleep duration regardless of insomnia symptoms, while the association with short sleep duration was significant only if insomnia symptoms were present. Conclusions: Both short and long sleep duration, as well as insomnia symptoms, are associated with obesity and central obesity. There is an important joint effect of sleep duration and insomnia symptoms and there is no association between insomnia symptoms and obesity, as long as a normal sleeping time can be attained. This indicates that sleep duration rather than insomnia symptoms per se is of importance for the relationship between sleep and obesity.

  • 55.
    Carlsson, Axel C.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden..
    Bandstein, Nadia
    Karolinska Univ Hosp, Dept Emergency Med, C1-63, S-14186 Stockholm, Sweden.;Karolinska Inst, Dept Internal Med, Stockholm, Sweden..
    Roos, Andreas
    Karolinska Univ Hosp, Dept Emergency Med, C1-63, S-14186 Stockholm, Sweden.;Karolinska Inst, Dept Internal Med, Stockholm, Sweden..
    Hammarsten, Ola
    Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Clin Chem & Transfus Med, Gothenburg, Sweden..
    Holzmann, Martin J.
    Karolinska Univ Hosp, Dept Emergency Med, C1-63, S-14186 Stockholm, Sweden.;Karolinska Inst, Dept Internal Med, Stockholm, Sweden..
    High-sensitivity cardiac troponin T levels in the emergency department in patients with chest pain but no myocardial infarction2017In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 228, p. 253-259Article in journal (Refereed)
    Abstract [en]

    Background: High-sensitivity cardiac troponin T (hs-cTnT) was recently introduced into clinical practice. The increased sensitivity has decreased the specificity. We aimed to determine the predictors for and prevalence of hs-cTnT levels above the 99th percentile in a stable population of patients without myocardial infarction (MI) who sought medical attention for chest pain in the emergency department. Methods: We included 11,847 patients with chest pain and at least one hs-cTnT measurement during 2011 and 2012. Patients with any acute reasons for an elevated hs-cTnT level were excluded. We used logistic regression to calculate adjusted odds ratios with 95% confidence intervals for the association between patient characteristics and hs-cTnT levels of >14 ng/L. We also determined 50th, 75th, 97.5th, and 99th percentile values of hs-cTnT levels in relation to age, sex, estimated glomerular filtration rate (eGFR), and presence or absence of comorbidities. Results: In total, 1360 (11%) patients had hs-cTnT levels of >14 ng/L. Men had higher troponin levels than women, and older patients had higher levels than younger patients. The strongest predictor of an elevated troponin level was a reduced eGFR. The 99th percentile for hs-cTnT among all men and among women <50 years of age with normal renal function was 20 and 12 ng/L, respectively; this level increased to 44 and 36 ng/L, respectively, at the age of 70-79 years. Conclusions: A hs-cTnT level above the 99th percentile in patients with chest pain but no MI is common and is related to sex, age, and eGFR.

  • 56.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Calamia, Michael
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Helmersson-Karlqvist, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Kidney injury molecule (KIM)-1 is associated with insulin resistance: Results from two community-based studies of elderly individuals2014In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 103, no 3, p. 516-521Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND OBJECTIVES: Insulin resistance has been shown to be closely associated with glomerular filtration rate and urinary albumin/creatinine ratio, even prior to the development of diabetes. Urinary kidney injury molecule 1 (KIM-1) is a novel, highly specific marker of kidney tubular damage. The role of insulin resistance in the development of kidney tubular damage is not previously reported. Thus, we aimed to investigate the associations between insulin sensitivity (assessed by HOMA) and urinary KIM-1.

    DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: Two community-based cohorts of elderly individuals were investigated: Prospective Investigation of the vasculature in Uppsala seniors (PIVUS, n=701; mean age 75 years, 52% women); and Uppsala Longitudinal Study of adult men (ULSAM, n=533; mean age 78 years).

    RESULTS: Lower insulin sensitivity was associated with higher urinary KIM-1 in both cohorts after adjustments for age, BMI, blood pressure, antihypertensive treatment, glomerular filtration rate, and urinary albumin-creatinine ratio (PIVUS: regression coefficient for 1-SD higher HOMA-IR 0.11, 95% CI 0.03-0.20, p=0.009, and ULSAM: 0.13, 95% CI 0.04-0.22, p=0.007). Results were similar in individuals without diabetes, with normal kidney function and normo-albuminuria.

    CONCLUSIONS: Our findings in elderly individuals support the notion that the interplay between an impaired glucose metabolism and renal tubular damage is evident even prior to the development of diabetes and overt kidney disease.

    Download full text (pdf)
    fulltext
  • 57.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Carrero, Juan-Jesús
    Stenvinkel, Peter
    Bottai, Matteo
    Barany, Peter
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Endostatin, Cathepsin S, and Cathepsin L, and Their Association with Inflammatory Markers and Mortality in Patients Undergoing Hemodialysis2015In: Blood Purification, ISSN 0253-5068, E-ISSN 1421-9735, Vol. 39, no 4, p. 259-265Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/AIMS: Although both endostatin and cathepsins S have been associated with higher mortality, data in patients with end-stage renal disease (ESRD) are scarce.

    METHODS: A longitudinal cohort study of 207 prevalent patients undergoing hemodialysis.

    RESULTS: Cathepsins S and L were associated with soluble receptors for tumor necrosis factor (sTNFR1 and sTNFR2, rho between 0.28 and 0.43, p < 0.001 for all). Weaker or absent associations between endostatin, cathepsins S and L were seen with other inflammatory biomarkers, that is, CRP, interleukin 6, pentraxin 3, and TNF. In Cox and Laplace regression models adjusted for age, sex, dialysis vintage, and diabetes: standard deviation increments of endostatin was associated with a lower mortality (hazard ratio 0.75, 95% confidence interval (CI) 0.57-0.98), and with 6.8 months longer median survival.

    CONCLUSIONS: The high levels of endostatin, cathepsins S and L, and their associations with sTNFR1 and sTNFR2 warrant further studies exploring mortality, and the angiogenic and inflammatory pathways in ESRD.

    Download full text (pdf)
    fulltext
  • 58.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Carrero, Juan-Jesús
    Stenvinkel, Peter
    Bottai, Matteo
    Barany, Peter
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    High levels of soluble tumor necrosis factor receptors 1 and 2 and their association with mortality in patients undergoing hemodialysis2015In: Cardiorenal medicine, ISSN 1664-3828, Vol. 5, no 2, p. 89-95Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Circulating soluble tumor necrosis factor receptors 1 and 2 (sTNFR1 and sTNFR2) are associated with chronic kidney disease (CKD) progression in patients with CKD or diabetes, and with higher mortality. However, data in patients with end-stage renal disease are scarce. Therefore, we analyzed serum levels of sTNFR1 and sTNFR2 and investigated their association with inflammatory markers and mortality in dialysis patients.

    RESEARCH DESIGN AND METHODS: This was a longitudinal cohort study of 207 prevalent patients (median age 66 years, 56% men) undergoing hemodialysis in Stockholm, Sweden. Demographics, clinical characteristics, including comorbidities and laboratory data, were obtained at baseline, together with prospective follow-up for mortality.

    RESULTS: The median sTNFR1 and sTNFR2 levels were 17,680 ng/l [95% confidence interval (CI) 17,023-18,337] and 24,450 ng/l (95% CI 23,721-25,179), respectively. During a follow-up of 31 months (interquartile range, 21-38), 77 patients died. There was no association between the levels of sTNFRs and mortality in Cox regression models, and no consistent trend towards higher or lower mortality was seen in Laplace regression models. sTNFR1 and sTNFR2 levels were highly associated with other inflammatory markers including interleukin-6, pentraxin 3 and TNF-α.

    CONCLUSIONS: Prevalent hemodialysis patients have several-fold higher levels of sTNFRs compared to previous studies in CKD stage 4 patients. As no consistent association between TNFR and mortality was observed, clinical implications of measuring these receptors to predict outcome end-stage renal disease patients provide limited results.

  • 59.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Carrero, Juan Jesus
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Feldreich, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Stenemo, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Use of Proteomics To Investigate Kidney Function Decline over 5 Years2017In: American Society of Nephrology. Clinical Journal, ISSN 1555-9041, E-ISSN 1555-905X, Vol. 12, no 8, p. 1226-1235Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND OBJECTIVES: Using a discovery/replication approach, we investigated associations between a multiplex panel of 80 circulating proteins associated with cardiovascular pathology or inflammation, and eGFR decline per year and CKD incidence.

    DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used two cohorts, the Prospective Investigation of the Vasculature in Uppsala Seniors Study (PIVUS; n=687, mean age of 70 years, 51% women) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=360 men, mean age of 78 years), with 5-year follow-up data on eGFR. There were 231 and 206 incident cases of CKD during follow-up in the PIVUS and ULSAM studies, respectively. Proteomic profiling of 80 proteins was assessed by a multiplex assay (proximity extension assay). The assay uses two antibodies for each protein and a PCR step to achieve a high-specific binding and the possibility to measure multiple proteins in parallel, but gives no absolute concentrations.

    RESULTS: In the discovery cohort from the PIVUS Study, 28 plasma proteins were significantly associated with eGFR decline per year, taking into account the multiple testing. Twenty of these proteins were significantly associated with eGFR decline per year in the replication cohort from the ULSAM Study after adjustment for age, sex, cardiovascular risk factors, medications, and urinary albumin-to-creatinine ratio (in order of significance: TNF-related apoptosis-inducing ligand receptor 2*, CD40L receptor, TNF receptor 1*, placenta growth factor*, thrombomodulin*, urokinase plasminogen activator surface receptor*, growth/differentiation factor 15*, macrophage colony-stimulating factor 1, fatty acid-binding protein*, cathepsin D, resistin, kallikrein 11*, C-C motif chemokine 3, proteinase-activated receptor 1*, cathepsin L, chitinase 3-like protein 1, TNF receptor 2*, fibroblast growth factor 23*, monocyte chemotactic protein 1, and kallikrein 6). Moreover, 11 of the proteins predicted CKD incidence (marked with * above). No protein consistently predicted eGFR decline per year independently of baseline eGFR in both cohorts.

    CONCLUSIONS: Several circulating proteins involved in phosphate homeostasis, inflammation, apoptosis, extracellular matrix remodeling, angiogenesis, and endothelial dysfunction were associated with worsening kidney function. Multiplex proteomics appears to be a promising way of discovering novel aspects of kidney disease pathology.

  • 60.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Centre for Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Jansson, Jan-Håkan
    Department of Public Health and Clinical Medicine, Research Unit Skellefteå, Umeå University, Umeå, Sweden.
    Söderberg, Stefan
    Department of Public Health and Clinical Medicine, Heart Centre, Umeå University, Umeå, Sweden.
    Ruge, Toralph
    Dept of Medicine Solna, Karolinska Institutet and Function of Emergency Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Ärnlöv, Johan
    Centre for Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden; School of Health and Social Sciences, Dalarna University, Falun, Sweden.
    Levels of soluble tumor necrosis factor receptor 1 and 2, gender, and risk of myocardial infarction in Northern Sweden2018In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 272, p. 41-46Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS:

    Soluble receptors for tumor necrosis factor alpha (sTNFR1 and sTNFR2) have been associated with cardiovascular diseases, and some evidence points towards a difference in associated risk between men and women. We aimed to study the association between sTNFR1 and sTNFR2 and incident myocardial infarctions (MI) and to explore the influence of established cardiovascular risk factors in men and women.

    METHODS:

    We conducted a nested case control study in three large Swedish cohorts, including 533 myocardial infarction cases, and 1003 age-, sex- and cohort-matched controls. Odds ratios (OR) with 95% confidence intervals (CI) were calculated.

    RESULTS:

    An association between circulating sTNFR1 and sTNFR2 and an increased risk for MI was found when comparing cases and controls. The odds ratios were significant after adjustment for established cardiovascular risk factors and C-reactive protein in women (OR 1.44, 95% CI 1.08-1.93 for TNFR1, and 1.61, 95% CI 1.11-2.34 for TNFR2), but was abolished in men. Women with a combination of elevated CRP and values in the upper quartile of TNFR1 or TNFR2 had a 5-fold higher risk of myocardial infarction versus those with normal CRP and values in the lower three quartiles of TNFR1 or TNFR2.

    CONCLUSIONS:

    As the risk estimates for TNFR1 and TNFR2 were higher and remained significant after adjustments for established cardiovascular risk factors in women but not in men, a potential role for TNFR1 and TNFR2 in identifying women with a higher MI risk is possible. The future clinical role of TNFR1 and TNFR2 in combination with CRP to identify high risk patients for coronary heart disease has yet to be determined.

  • 61.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Juhlin, C Christofer
    Larsson, Tobias E
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Soluble tumor necrosis factor receptor 1 (sTNFR1) is associated with increased total mortality due to cancer and cardiovascular causes: Findings from two community based cohorts of elderly2014In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 237, no 1, p. 236-242Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Experimental evidence support soluble receptors for tumor necrosis factor alpha as important mediators of the underlying pathology leading to cardiovascular disease and cancer. However, prospective data concerning the relation between circulating soluble tumor necrosis factor receptor-1 (sTNFR1) and mortality in humans are lacking. We aimed to explore and validate the association between sTNFR1 and mortality, and to explore the influence of other established risk factors for mortality, including other inflammatory markers.

    METHODS: The association between serum sTNFR1and the risk for mortality was investigated in two community-based cohorts of elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 50%, n = 1005, mean age 70 years, median follow-up 7.9 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 775, mean age 77 years, median follow-up 8.1 years).

    RESULTS: In total, 101 participants in PIVUS and 274 in ULSAM died during follow-up. In multivariable Cox regression models adjusted for inflammation, lifestyle and established cardiovascular risk factors, one standard deviation (SD) higher sTNFR1 was associated with a hazard ratio (HR) for mortality of 1.37, 95% confidence interval (CI) 1.17-1.60, in PIVUS and HR 1.22, 95% CI 1.10-1.37 in ULSAM. Moreover, circulatingsTNFR1 was associated with cardiovascular mortality (HR per SD of sTNFR1, 1.24, 95% CI 1.07-1.44) and cancer mortality (HR per SD of sTNFR1, 1.32, 95% CI 1.11-1.57) in the ULSAM cohort. High levels of sTNFR1 identified individuals with increased risk of mortality among those with high as well as low levels of systemic inflammation.

    CONCLUSIONS: An association between circulating sTNFR1 and an increased risk for mortality was found and validated in two independent community-based cohorts. The future clinical role of sTNFR1 to identify high risk patients for adverse outcomes and mortality has yet to be determined.

    Download full text (pdf)
    fulltext
  • 62.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Helmersson-Karlqvist, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Larsson, Tobias E
    Bottai, Matteo
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Urinary Kidney Injury Molecule-1 and the Risk of Cardiovascular Mortality in Elderly Men2014In: Clinical journal of the American Society of Nephrology : CJASN, ISSN 1555-905X, Vol. 9, no 8, p. 1393-1401Article in journal (Refereed)
    Abstract [en]

    Background and objectives

    Kidney injury molecule-1 (KIM-1) has been suggested as a clinically relevant highly specific biomarker of acute kidney tubular damage. However, community-based data on the association between urinary levels of KIM-1 and the risk for cardiovascular mortality are lacking. This study aimed to investigate the association between urinary KIM-1 and cardiovascular mortality.

    Design, setting, participants, & measurements

    This was a prospective study, using the community-based Uppsala Longitudinal Study of Adult Men (N=590; mean age 77 years; baseline period, 1997–2001; median follow-up 8.1 years; end of follow-up, 2008).

    Results

    During follow-up, 89 participants died of cardiovascular causes (incidence rate, 2.07 per 100 person-years at risk). Models were adjusted for cardiovascular risk factors (age, systolic BP, diabetes, smoking, body mass index, total cholesterol, HDL cholesterol, antihypertensive treatment, lipid-lowering treatment, aspirin treatment, and history of cardiovascular disease) and for markers of kidney dysfunction and damage (cystatin C–based eGFR and urinary albumin/creatinine ratio). Higher urinary KIM-1/creatinine (from 24-hour urine collections) was associated with a higher risk for cardiovascular mortality (hazard ratio per SD increase, 1.27; 95% confidence interval [95% CI], 1.05 to 1.54; P=0.01). Participants with a combination of high KIM-1/creatinine (upper quintile, ≥175 ng/mmol), low eGFR (≤60 ml/min per 1.73 m2), and microalbuminuria/macroalbuminuria (albumin/creatinine ratio≥3 g/mol) had a >8-fold increased risk compared with participants with low KIM-1/creatinine (<175 ng/mmol), normal eGFR (>60 ml/min per 1.73 m2), and normoalbuminuria (albumin/creatinine ratio<3 g/mol) (hazard ratio, 8.56; 95% CI, 4.17 to 17.56; P<0.001).

    Conclusions

    These findings suggest that higher urinary KIM-1 may predispose to a higher risk of cardiovascular mortality independently of established cardiovascular risk factors, eGFR, and albuminuria. Additional studies are needed to further assess the utility of measuring KIM-1 in the clinical setting.

    Download full text (pdf)
    fulltext
  • 63.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Larsson, Tobias E
    Helmersson-Karlqvist, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Soluble TNF Receptors and Kidney Dysfunction in the Elderly2014In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 25, no 6, p. 1313-1320Article in journal (Refereed)
    Abstract [en]

    The importance of TNF-α and its soluble receptors (sTNFR1 and sTNFR2) in the development of kidney disease is being unraveled. Yet, community-based data regarding the role of sTNFRs are lacking. We assessed serum sTNFRs and aspects of kidney damage cross-sectionally in two independent community-based cohorts of elderly participants: Prospective Investigation of the Vasculature in Uppsala Seniors (n=815; mean age, 75 years; 51% women) and Uppsala Longitudinal Study of Adult Men (n=778; mean age, 78 years). Serum sTNFR1 correlated substantially with different aspects of kidney pathology in the Uppsala Longitudinal Study of Adult Men cohort (R=-0.52 for estimated GFR, R=0.22 for urinary albumin-to-creatinine ratio, and R=0.17 for urinary kidney injury molecule-1; P<0.001 for all), with similar correlations in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort. These associations remained significant after adjustment for age, sex, inflammatory markers, and cardiovascular risk factors and were also evident in participants without diabetes. Serum sTNFR2 was associated with all three markers in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort (P<0.001 for all). Our findings from two independent community-based cohorts confirm and extend results of previous studies supporting circulating sTNFRs as relevant biomarkers for kidney damage and dysfunction in elderly individuals, even in the absence of diabetes.

    Download full text (pdf)
    fulltext
  • 64.
    Carlsson, Axel C.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden..
    Li, Xinjun
    Lund Univ, Ctr Primary Hlth Care Res, Malmo, Sweden..
    Holzmann, Martin J.
    Karolinska Univ Hosp, Dept Emergency Med, Stockholm, Sweden.;Karolinska Inst, Dept Internal Med, S-10401 Stockholm, Sweden..
    Wändell, Per
    Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden..
    Gasevic, Danijela
    Univ Edinburgh, Coll Med & Vet Med, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland..
    Sundquist, Jan
    Lund Univ, Ctr Primary Hlth Care Res, Malmo, Sweden..
    Sundquist, Kristina
    Lund Univ, Ctr Primary Hlth Care Res, Malmo, Sweden..
    Neighbourhood socioeconomic status and coronary heart disease in individuals between 40 and 50 years2016In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 102, no 10, p. 775-782Article in journal (Refereed)
    Abstract [en]

    Objective The incidence of myocardial infarction (MI) has decreased in general but not among younger middle-aged adults. We performed a cohort study of the association between neighbourhood socioeconomic status (SES) at the age of 40 and risk of MI before the age of 50 years.

    Methods All individuals in Sweden were included in the year of their 40th birthday, if it occurred between 1998 and 2010. National registers were used to categorise neighbourhood SES into high, middle and low, and to retrieve information on incident MI and coronary heart disease (CHD). Cox regression models, adjusted for marital status, education level, immigrant status and region of residence, provided an estimate of the HRs and 95% CIs for MI or CHD.

    Results Out of 587 933 men and 563 719 women, incident MI occurred in 2877 (0.48%) men and 932 (0.17%) women; and CHD occurred in 4400 (0.74%) men and 1756 (0.31%) women during a mean follow-up of 5.5 years. Using individuals living in middle-SES neighbourhoods as referents, living in high-SES neighbourhoods was associated with lower risk of MI in both sexes (HR (95% CI): men: 0.72 (0.64 to 0.82), women: 0.66 (0.53 to 0.81)); living in low-SES neighbourhoods was associated with a higher risk of MI (HR (95% CI): men: 1.31 (1.20 to 1.44), women: 1.28 (1.08 to 1.50)). Similar risk estimates for CHD were found.

    Conclusions The results of our study suggest an increased risk of MI and CHD among residents from low-SES neighbourhoods and a lower risk in those from high-SES neighbourhoods compared with residents in middle-SES neighbourhoods.

  • 65.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Huddinge, Sweden.
    Li, Xinjun
    Lund Univ, Ctr Primary Hlth Care Res, Malmo, Sweden..
    Holzmann, Martin J.
    Karolinska Univ Hosp, Dept Emergency Med, Stockholm, Sweden.;Karolinska Inst, Dept Internal Med, Stockholm, Sweden..
    Ärnlov, Johan
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Huddinge, Sweden.;Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden..
    Wändell, Per
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Huddinge, Sweden..
    Gasevic, Danijela
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Coll Med & Vet Med, Edinburgh, Midlothian, Scotland..
    Sundquist, Jan
    Lund Univ, Ctr Primary Hlth Care Res, Malmo, Sweden..
    Sundquist, Kristina
    Lund Univ, Ctr Primary Hlth Care Res, Malmo, Sweden..
    Neighborhood socioeconomic status at the age of 40 years and ischemic stroke before the age of 50 years: A nationwide cohort study from Sweden2017In: International Journal of Stroke, ISSN 1747-4930, E-ISSN 1747-4949, Vol. 12, no 8, p. 815-826Article in journal (Refereed)
    Abstract [en]

    Objective: We aimed to study the association between neighborhood socioeconomic status at the age of 40 years and risk of ischemic stroke before the age of 50 years.

    Methods: All individuals in Sweden were included if their 40th birthday occurred between 1998 and 2010. National registers were used to categorize neighborhood socioeconomic status into high, middle, and low and to retrieve information on incident ischemic strokes. Hazard ratios and their 95% confidence intervals were estimated.

    Results: A total of 1,153,451 adults (women 48.9%) were followed for a mean of 5.5 years (SD 3.5 years), during which 1777 (0.30%) strokes among men and 1374 (0.24%) strokes among women were recorded. After adjustment for sex, marital status, education level, immigrant status, region of residence, and neighborhood services, there was a lower risk of stroke in residents from high-socioeconomic status neighborhoods (hazard ratio 0.87, 95% confidence interval 0.78-0.96), and an increased risk of stroke in adults from low-socioeconomic status neighborhoods (hazard ratio 1.16, 95% confidence interval 1.06-1.27), compared to their counterparts living in middle-socioeconomic status neighborhoods. After further adjustment for hospital diagnoses of hypertension, diabetes, heart failure, and atrial fibrillation prior to the age of 40, the higher risk in neighborhoods with low socioeconomic status was attenuated, but remained significant (hazard ratio 1.12, 95% confidence interval 1.02-1.23).

    Conclusions: In a nationwide study of individuals between 40 and 50 years, we found that the risk of ischemic stroke differed depending on neighborhood socioeconomic status, which calls for increased efforts to prevent cardiovascular diseases in low socioeconomic status neighborhoods.

  • 66.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Division of Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Nordquist, Lina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Larsson, Tobias E.
    Carrero, Juan-Jesús
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. gSchool of Health and Social Studies, Dalarna University, Falun , Sweden.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Soluble Tumor Necrosis Factor Receptor 1 Is Associated with Glomerular Filtration Rate Progression and Incidence of Chronic Kidney Disease in Two Community-Based Cohorts of Elderly Individuals2015In: Cardiorenal Medicine, ISSN 1664-3828, Vol. 5, no 4, p. 278-288Article in journal (Refereed)
    Abstract [en]

    Objective: We aimed to explore and validate the longitudinal associations between soluble tumor necrosis factor receptor 1 (sTNFR1), glomerular filtration rate (GFR) progression, and chronic kidney disease (CKD) incidence in two independent community-based cohorts of elderly individuals with prespecified subgroup analyses in individuals without prevalent diabetes. Research Design and Methods: Two community-based cohorts of elderly individuals were used with 5-year follow-up data on estimated GFR: the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 437 men; mean age: 78 years) and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 703; mean age: 70 years; 51% women). GFR categories were defined as >= 60, 30-60, and = 60 ml/min/1.73 m(2) at baseline, higher sTNFRs were associated with incident CKD after 5 years in both cohorts [ULSAM: OR per SD increase 1.49 (95% CI 1.16-1.9) and PIVUS: OR 1.84 (95% CI 1.50-2.26)]. Associations were similar in individuals without diabetes. Conclusions: Higher circulating sTNFR1 independently predicts the progression to a worse GFR category and CKD incidence in elderly individuals even in the absence of diabetes. Further studies are warranted to investigate the underlying mechanisms, and to evaluate the clinical relevance of our findings.

  • 67.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ruge, Toralph
    Kjøller, Erik
    Hilden, Jørgen
    Kolmos, Hans Jørn
    Sajadieh, Ahmad
    Kastrup, Jens
    Jensen, Gorm Boje
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Nowak, Christoph
    Jakobsen, Janus Christian
    Winkel, Per
    Gluud, Christian
    Ärnlöv, Johan
    10-Year Associations between Tumor Necrosis Factor Receptors 1 and 2 and Cardiovascular Events in Patients with Stable Coronary Heart Disease: A CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) Trial Substudy.2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 9, article id e008299Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We aimed to assess the associations and predictive powers between the soluble receptors for tumor necrosis factor (TNF)-α (TNFR1 and TNFR2) and cardiovascular outcomes in patients with stable coronary heart disease.

    METHODS AND RESULTS: CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) is a randomized clinical trial comparing clarithromycin with placebo in patients with stable coronary heart disease. The primary outcome was a composite of nonfatal acute myocardial infarction, unstable angina pectoris, cerebrovascular disease, and all-cause mortality. Patients were followed up for 10 years; discovery sample, those assigned placebo (1204 events in n=1998); and replication sample, those assigned clarithromycin (1220 events in n=1979). We used Cox regression adjusted for C-reactive protein level, established cardiovascular risk factors, kidney function, and cardiovascular drugs. After adjustments, higher serum levels of TNFR1 and TNFR2 were associated with the composite outcome in the discovery sample (hazard ratio per SD increase, 1.13; 95% confidence interval, 1.05-1.22; P=0.001 for TNFR1; hazard ratio, 1.16; 95% confidence interval, 1.08-1.24; P<0.001 for TNFR2). The associations were similar in the replication sample. The associations with the composite outcome were mainly driven by acute myocardial infarction, cardiovascular mortality, and noncardiovascular mortality. The addition of TNFR1 and TNFR2 to established cardiovascular risk factors improved prediction only modestly (<1%).

    CONCLUSIONS: Increased concentrations of circulating TNFR1 and TNFR2 were associated with increased risks of cardiovascular events and mortality in patients with stable coronary heart disease. Yet, the utility of measuring TNFR1 and TNFR2 to improve risk prediction in these patients appears limited.

    CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00121550.

  • 68.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ruge, Toralph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Association between circulating endostatin, hypertension duration, and hypertensive target-organ damage2013In: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 62, no 6, p. 1146-1151Article in journal (Refereed)
    Abstract [en]

    Our aim is to study associations between circulating endostatin, hypertension duration, and hypertensive target-organ damage. Long-term hypertension induces cardiovascular and renal remodeling. Circulating endostatin, a biologically active derivate of collagen XVIII, has been suggested to be a relevant marker for extracellular matrix turnover and remodeling in various diseases. However, the role of endostatin in hypertension and hypertensive target-organ damage is unclear. Serum endostatin was measured in 2 independent community-based cohorts: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 51%; n=812; mean age, 75 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=785; mean age, 77.6 years). Retrospective data on blood pressure measurements and antihypertensive medication (PIVUS >5 years, ULSAM >27 years), and cross-sectional data on echocardiographic left ventricular mass, endothelial function (endothelium-dependent vasodilation assessed by the invasive forearm model), and urinary albumin/creatinine ratio were available. In PIVUS, participants with ≥5 years of history of hypertension portrayed 0.42 SD (95% confidence interval, 0.23-0.61; P<0.001) higher serum endostatin, compared with that of normotensives. This association was replicated in ULSAM, in which participants with 27 years hypertension duration had the highest endostatin (0.57 SD higher; 95% confidence interval, 0.35-0.80; P<0.001). In addition, higher endostatin was associated with higher left ventricular mass, worsened endothelial function, and higher urinary albumin/creatinine ratio (P<0.03 for all) in participants with prevalent hypertension. Circulating endostatin is associated with the duration of hypertension, and vascular, myocardial, and renal indices of hypertensive target-organ damage. Further studies are warranted to assess the prognostic role of endostatin in individuals with hypertension.

    Download full text (pdf)
    fulltext
  • 69.
    Carlsson, Axel C.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Div Family Med, Dept Neurobiol, Care Sci & Soc, Karlskrona, Sweden..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Carrero, Juan Jesus
    Karolinska Inst, Div Renal Med, Dept Clin Sci, Intervent & Technol, Karlskrona, Sweden..
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Stenemo, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Dalarna Univ, Sch Hlth & Social Sci, Dalarna, Sweden..
    Use of a proximity extension assay proteomics chip to discover new biomarkers associated with albuminuria2017In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, no 4, p. 340-348Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The underlying mechanisms for the development of albuminuria and the increased cardiovascular risk in patients with elevated albuminuria levels are incompletely understood. We therefore investigated the associations between 80 cardiovascular proteins and the urinary albumin to creatinine ratio (ACR).

    METHODS: We used a discovery/replication approach in two independent community-based cohorts of elderly patients: the Uppsala Longitudinal Study of Adult Men (n = 662; mean age 78 years) and the Prospective Investigation of the Vasculature in Uppsala Seniors (n = 757; mean age 75 years; 51% women). A proteomic chip with a panel of 80 plasma proteins associated with different aspects of cardiovascular disease was analysed. In the discovery cohort, we used a false discovery rate of 5% to take into account the multiple statistical testing. Nominal p values were used in the replication.

    RESULTS: Higher levels of T-cell immunoglobulin mucin-1, placenta growth factor, growth/differentiation factor-15, urokinase plasminogen activator surface receptor and kallikrein-11 were robustly associated with a higher ACR in both cohorts in multivariable linear regression models adjusted for sex, established cardiovascular risk factors, antihypertensive treatment, prevalent cardiovascular disease and glomerular filtration rate (p < 0.02 for all). All associations were also significant in separate analyses of patients without diabetes.

    CONCLUSIONS: We discovered and replicated associations between ACR and five cardiovascular proteins involved in tubular injury, atherosclerosis, endothelial function, heart failure, inflammation, glomerulosclerosis and podocyte injury. Our findings put forward multiplex proteomics as a promising approach to explore novel aspects of the complex detrimental interplay between kidney function and the cardiovascular system.

  • 70.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Physical activity, obesity and risk of cardiovascular disease in middle-aged men during a median of 30 years of follow-up2016In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 23, no 4, p. 359-365Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    We aimed to investigate associations between combinations of body mass index (BMI)-categories, levels of physical activity and long-term risk of cardiovascular disease.

    METHOD AND RESULTS:

    At age 50 years, cardiovascular risk factors were assessed in 2196 participating men of the ULSAM-study. This investigation was repeated at age 60, 70, 77 and 82 years. Being physically active (PA) was defined as three hours of recreational or hard physical training per week. The men were categorized according to BMI/PA-status, as PA/normal weight (n = 593 at baseline), non-PA/normal weight (BMI < 25 kg/m(2), n = 580), PA/overweight (n = 418), non-PA/overweight (BMI 25-30 kg/m(2), n = 462), PA/obese (n = 62), non-PA/obese (BMI >30 kg/m(2), n = 81). We used updated data on BMI and physical activity obtained at all examinations. During follow-up (median 30 years) 850 individuals suffered a cardiovascular disease (myocardial infarction, stroke or heart failure). Using updated data on BMI/PA categories, an increased risk for cardiovascular disease was seen with increasing BMI, but a high physical activity was associated with a lower risk of cardiovascular disease within each BMI category: non-PA/normal weight (hazard ratio (HR) 1.31, 95% confidence interval (CI) 1.04-1.66), PA/overweight (HR 1.52, 95% CI 1.20-1.94), non-PA/overweight (HR 1.65, 95% CI 1.31-2.07) PA/obese (HR 2.05, 95% CI 1.44-2.92) and non-PA/obese (HR 2.39, 95% CI 1.74-3.29), using PA/normal weight men as referent.

    CONCLUSIONS:

    Although physical activity was beneficial at all levels of BMI regarding the risk of future cardiovascular disease, there was still a substantial increased risk associated with being overweight or obese during 30 years of follow-up.

  • 71.
    Carlsson, Axel C.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden..
    Östgren, C. J.
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Lanne, T.
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Nyström, F. H.
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden..
    The association between endostatin and kidney disease and mortality in patients with type 2 diabetes2016In: Diabetes & Metabolism, ISSN 1262-3636, E-ISSN 1878-1780, Vol. 42, no 5, p. 351-357Article in journal (Refereed)
    Abstract [en]

    Aim. - Circulating endostatin, a biologically active derivate of collagen XVIII, is considered to be a marker of kidney disease and a risk factor for its related mortality. However, less is known of the role of endostatin in diabetes and the development of diabetic nephropathy. For this reason, our study investigated the associations between circulating endostatin and the prevalence and progression of kidney disease, and its mortality risk in patients with type 2 diabetes (T2D). Methods. - This was a cohort study of 607 patients with T2D (mean age: 61 years, 44% women). Estimated glomerular filtration rate (eGFR), calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation, was used to assess the patients' kidney function decline and mortality. Results. - Of the total study cohort, 20 patients declined by >= 20% in eGFR over 4 years, and 44 died during the follow-up (mean duration: 6.7 years). At baseline, participants with diabetic nephropathy (defined as eGFR < 60 mL/min/1.73 m(2)) and/or microalbuminuria [defined as a urinary albumin-to-creatinine ratio (ACR) > 3 g/mol] had higher median levels of endostatin than those without nephropathy (62.7 mu g/L vs 57.4 mu g/L, respectively; P = 0.031). In longitudinal analyses adjusted for age, gender, baseline eGFR and ACR, higher endostatin levels were associated with a higher risk of decline (>= 20% in eGFR, OR per 1 SD increase: 1.73, 95% CI: 1.13-2.65) and a higher risk of mortality (HR per 1 SD increase: 1.57, 95% CI: 1.19-2.07). Conclusion. - In patients with T2D, circulating endostatin levels can predict the progression of kidney disease and mortality independently of established kidney disease markers. The clinical usefulness of endostatin as a risk marker in such patients merits further studies.

  • 72.
    Carlsson, Axel C.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Östgren, Carl Johan
    Department of Medical and Health Sciences, Linköping University, Linköping, Sweden..
    Nystrom, Fredrik H
    Department of Medical and Health Sciences, Linköping University, Linköping, Sweden..
    Länne, Toste
    Department of Medical and Health Sciences, Linköping University, Linköping, Sweden..
    Jennersjö, Pär
    Department of Medical and Health Sciences, Linköping University, Linköping, Sweden..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Association of soluble tumor necrosis factor receptors 1 and 2 with nephropathy, cardiovascular events, and total mortality in type 2 diabetes2016In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 15, article id 40Article in journal (Refereed)
    Abstract [en]

    AIMS/HYPOTHESIS: Soluble tumor necrosis factor receptors 1 and 2 (sTNFR1 and sTNFR2) contribute to experimental diabetic kidney disease, a condition with substantially increased cardiovascular risk when present in patients. Therefore, we aimed to explore the levels of sTNFRs, and their association with prevalent kidney disease, incident cardiovascular disease, and risk of mortality independently of baseline kidney function and microalbuminuria in a cohort of patients with type 2 diabetes. In pre-defined secondary analyses we also investigated whether the sTNFRs predict adverse outcome in the absence of diabetic kidney disease.

    METHODS: The CARDIPP study, a cohort study of 607 diabetes patients [mean age 61 years, 44 % women, 45 cardiovascular events (fatal/non-fatal myocardial infarction or stroke) and 44 deaths during follow-up (mean 7.6 years)] was used.

    RESULTS: Higher sTNFR1 and sTNFR2 were associated with higher odds of prevalent kidney disease [odd ratio (OR) per standard deviation (SD) increase 1.60, 95 % confidence interval (CI) 1.32-1.93, p < 0.001 and OR 1.54, 95 % CI 1.21-1.97, p = 0.001, respectively]. In Cox regression models adjusting for age, sex, glomerular filtration rate and urinary albumin/creatinine ratio, higher sTNFR1 and sTNFR2 predicted incident cardiovascular events [hazard ratio (HR) per SD increase, 1.66, 95 % CI 1.29-2.174, p < 0.001 and HR 1.47, 95 % CI 1.13-1.91, p = 0.004, respectively]. Results were similar in separate models with adjustments for inflammatory markers, HbA1c, or established cardiovascular risk factors, or when participants with diabetic kidney disease at baseline were excluded (p < 0.01 for all). Both sTNFRs were associated with mortality.

    CONCLUSIONS/INTERPRETATIONS: Higher circulating sTNFR1 and sTNFR2 are associated with diabetic kidney disease, and predicts incident cardiovascular disease and mortality independently of microalbuminuria and kidney function, even in those without kidney disease. Our findings support the clinical utility of sTNFRs as prognostic markers in type 2 diabetes.

    Download full text (pdf)
    fulltext
  • 73.
    Cars, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Real-Time Monitoring of Healthcare Interventions in Routine Care: Effectiveness and Safety of Newly Introduced Medicines2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Before market authorization of new medicines, their efficacy and safety are evaluated using randomized controlled trials. While there is no doubt about the scientific value of randomized trials, they are usually conducted in selected populations with questionable generalizability to routine care. 

    In the digital data revolution era, with healthcare data growing at an unprecedented rate, drug monitoring in routine care is still highly under-utilized. Although many countries have access to data on prescription drugs at the individual level in ambulatory care, such data are often missing for hospitals. This is a growing problem considering the clear trend towards more new and expensive drugs administered in the hospital setting. The aim of this thesis was therefore to develop methods for extracting data on drug use from a hospital-based electronic health record system and further to build and evaluate models for real-time monitoring of effectiveness and safety of new drugs in routine care using data from electronic health records and regional and national health care registers.

    Using the developed techniques, we were able to demonstrate drug use and health service utilization for inflammatory bowel disease and to evaluate the comparative effectiveness and safety of antiarrhythmic drugs.

    With a rapidly evolving drug development, it is important to optimize the evaluation of effectiveness, safety and health economic value of new medicines in routine care. We believe that the models described in this thesis could contribute to fulfil this need.

    List of papers
    1. Extraction of Electronic Health Record Data in a Hospital Setting: Comparison of Automatic and Semi-Automatic Methods Using Anti-TNF Therapy as Model
    Open this publication in new window or tab >>Extraction of Electronic Health Record Data in a Hospital Setting: Comparison of Automatic and Semi-Automatic Methods Using Anti-TNF Therapy as Model
    Show others...
    2013 (English)In: Basic & Clinical Pharmacology & Toxicology, ISSN 1742-7835, E-ISSN 1742-7843, Vol. 112, no 6, p. 392-400Article in journal (Refereed) Published
    Abstract [en]

    There is limited experience and methods for extractions of drug therapy data from electronic health records (EHR) in the hospital setting. We have therefore developed and evaluated completeness and consistency of an automatic versus a semi-automatic extraction procedure applied on prescribing and administration of the TNF inhibitor infliximab using a hospital EHR system in Karolinska University Hospital, Sweden. Using two different extraction methods (automatic and semi-automatic), all administered infusions of infliximab between 2007 and 2010 were extracted from a database linked to the EHR system. Extracted data included encrypted personal identity number (PIN), date of birth, sex, time of prescription/administration, healthcare units, prescribed/administered dose and time of admission/discharge. The primary diagnosis (ICD-10) for the treatment with infliximab was extracted by linking infliximab infusions to their corresponding treatment episode. A total of 13,590 infusions of infliximab were administered during the period of 2007 to 2010. Of those were 13,531 (99.6%) possible to link to a corresponding treatment episode, and a primary diagnosis was extracted for 13,530 infusions. Information on encrypted PIN, date of birth, time of prescription/administration, time of admission/discharge and healthcare unit was complete. Information about sex was missing in one patient only. Calculable information about dosage was extracted for 13,300 (98.3%) of all linked infusions. This methodological study showed the potential to extract drug therapy data in a hospital setting. The semi-automatic procedure produced an almost complete pattern of demographics, diagnoses and dosages for the treatment with infliximab.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-202351 (URN)10.1111/bcpt.12055 (DOI)000319212100004 ()
    Available from: 2013-06-24 Created: 2013-06-24 Last updated: 2017-12-06Bibliographically approved
    2. Healthcare Utilisation and Drug Treatment in a Large Cohort of Patients with Inflammatory Bowel Disease
    Open this publication in new window or tab >>Healthcare Utilisation and Drug Treatment in a Large Cohort of Patients with Inflammatory Bowel Disease
    Show others...
    2016 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 10, no 5, p. 556-565Article in journal (Refereed) Published
    Abstract [en]

    Crohn's disease [CD] and ulcerative colitis [UC] are chronic diseases associated with a substantial utilisation of healthcare resources. We aimed to estimate the prevalence of inflammatory bowel disease [IBD], CD, and UC and to describe and compare healthcare utilisation and drug treatment in CD and UC patients. This was a cross-sectional study of all patients with a recorded IBD diagnosis in Stockholm County, Sweden. Data on outpatient visits, hospitalisations, surgeries, and drug treatment during 2013 were analysed. A total of 13 916 patients with IBD were identified, corresponding to an overall IBD prevalence of 0.65% [CD 0.27%, UC 0.35%, inflammatory bowel disease unclassified 0.04%]; 49% of all IBD patients were treated with IBD-related drugs. Only 3.6% of the patients received high-dose corticosteroids, whereas 32.4% were treated with aminosalicylates [CD 21.2%, UC 41.0%, p < 0.0001]. More CD patients were treated with biologicals compared with UC patients [CD 9.6%, UC 2.9%, p < 0.0001] and surgery was significantly more common among CD patients [CD 3.0%, UC 0.8%, p < 0.0001]. This study indicates that patients with CD are the group with the highest medical needs. Patients with CD utilised significantly more healthcare resources [including outpatient visits, hospitalisations, and surgeries] than UC patients. Twice as many CD patients received immunomodulators compared with UC patients and CD patients were treated with biologicals three times more often. These results highlight that CD remains a challenge and further efforts are needed to improve care in these patients.

    Keywords
    Inflammatory bowel disease, healthcare utilisation, drug treatment
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-298688 (URN)10.1093/ecco-jcc/jjv243 (DOI)000376391100008 ()26733406 (PubMedID)
    Available from: 2016-07-07 Created: 2016-07-06 Last updated: 2017-11-28Bibliographically approved
    3. An Automatized Model for Sequential Monitoring of Effectiveness of New Drugs using Dronedarone as Example
    Open this publication in new window or tab >>An Automatized Model for Sequential Monitoring of Effectiveness of New Drugs using Dronedarone as Example
    (English)Manuscript (preprint) (Other academic)
    Keywords
    comparative effectiveness research, comparative safety research, propensity score, dronedarone, flecainide, sequential monitoring
    National Category
    Cardiac and Cardiovascular Systems
    Research subject
    Pharmacoepidemiology
    Identifiers
    urn:nbn:se:uu:diva-304322 (URN)
    Available from: 2016-10-04 Created: 2016-10-04 Last updated: 2016-10-10
    4. Dronedarone and Hepatic Toxicity? A Model for Evaluation of Post-Marketing Safety of Drugs in Routine Care
    Open this publication in new window or tab >>Dronedarone and Hepatic Toxicity? A Model for Evaluation of Post-Marketing Safety of Drugs in Routine Care
    (English)Manuscript (preprint) (Other academic)
    Keywords
    dronedarone, amidoarone, safety, propensity score, liver enzyme
    National Category
    Cardiac and Cardiovascular Systems
    Research subject
    Pharmacoepidemiology
    Identifiers
    urn:nbn:se:uu:diva-304323 (URN)
    Available from: 2016-10-04 Created: 2016-10-04 Last updated: 2016-10-10
    Download full text (pdf)
    fulltext
    Download (jpg)
    preview image
  • 74.
    Cars, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lindhagen, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Malmstrom, Rickard E.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Div Clin Pharmacol, Stockholm, Sweden.
    Neovius, Martin
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden.
    Schwieler, Jonas
    Karolinska Inst, Dept Cardiol, Stockholm, Sweden.
    Wettermark, Bjorn
    Karolinska Inst, Dept Med, Ctr Pharmacoepidemiol, Stockholm, Sweden.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Dronedarone and Hepatic Toxicity?: A Model for Evaluation of Post-Marketing Safety of Drugs in Routine Care2017In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 26, p. 381-382Article in journal (Other academic)
  • 75.
    Cars, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Stockholm Cty Council, Publ Healthcare Serv Comm Adm, Stockholm, Sweden..
    Lindhagen, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Malmström, R. E.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Clin Pharmacol, Stockholm, Sweden..
    Neovius, M.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden..
    Schwieler, J.
    Karolinska Inst, Dept Cardiol, Stockholm, Sweden..
    Wettermark, B.
    Stockholm Cty Council, Publ Healthcare Serv Comm Adm, Stockholm, Sweden.;Karolinska Inst, Dept Med, Ctr Pharmacoepidemiol, Stockholm, Sweden..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Effectiveness of Drugs in Routine Care: A Model for Sequential Monitoring of New Medicines Using Dronedarone as Example2018In: Clinical Pharmacology and Therapeutics, ISSN 0009-9236, E-ISSN 1532-6535, Vol. 103, no 3, p. 493-501Article in journal (Refereed)
    Abstract [en]

    Although there is no doubt about the scientific value of randomized controlled clinical trials, they are usually conducted in selected populations different fromthose treated in clinical practice. Therefore, it is important to optimize real-time post-marketing evaluation of the effectiveness, safety, and cost of new drugs. Using electronic health records and administrative health databases froma well-defined region with universal access to healthcare, we have built a framework for real-time sequential monitoring of the effectiveness of newly marketed drugs in routine care. We chose the antiarrhythmic agent dronedarone as the study drug and flecainide as the comparator drug for illustration of the model. We demonstrate that this model produces consistent results with increasing precision over time as data accumulates in the clinical systems. We believe that use of this model at the introduction of new drugs can provide complementary evidence, especially in settings of adaptive licensing of new drugs.

  • 76.
    Cars, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lordal, Mikael
    Wettermark, Bjorn
    Using Administrative Healthcare Data to Study the Treatment of Inflammatory Bowel Disease in the Region of Stockholm, Sweden2014In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 23, no S1, p. 137-137Article in journal (Other academic)
  • 77.
    Cars, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Neovius, Martin
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Lindhagen, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Malmström, Rickard E.
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Schwieler, Jonas
    Karolinska Inst, Dept Cardiol, Stockholm, Sweden..
    Wettermark, Bjon
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    An Automatized Model for Sequential Monitoring of Effectiveness of New Drugs Using Dronedarone as Example2016In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 25, p. 504-504Article in journal (Refereed)
  • 78.
    Cars, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Dronedarone and Hepatic Toxicity? A Model for Evaluation of Post-Marketing Safety of Drugs in Routine CareManuscript (preprint) (Other academic)
  • 79.
    Cars, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Stockholm Cty Council, Publ Healthcare Serv Comm Adm, Stockholm, Sweden..
    Wettermark, Bjorn
    Stockholm Cty Council, Publ Healthcare Serv Comm Adm, Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden..
    Lofberg, Robert
    Karolinska Inst, Dept Med, Stockholm, Sweden.;IBD Unit Sophiahemmet, Stockholm, Sweden..
    Eriksson, Irene
    Stockholm Cty Council, Publ Healthcare Serv Comm Adm, Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lordal, Mikael
    Karolinska Inst, Dept Med, Stockholm, Sweden.;Karolinska Univ Hosp, Ctr Digest Dis, Stockholm, Sweden..
    Healthcare Utilisation and Drug Treatment in a Large Cohort of Patients with Inflammatory Bowel Disease2016In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 10, no 5, p. 556-565Article in journal (Refereed)
    Abstract [en]

    Crohn's disease [CD] and ulcerative colitis [UC] are chronic diseases associated with a substantial utilisation of healthcare resources. We aimed to estimate the prevalence of inflammatory bowel disease [IBD], CD, and UC and to describe and compare healthcare utilisation and drug treatment in CD and UC patients. This was a cross-sectional study of all patients with a recorded IBD diagnosis in Stockholm County, Sweden. Data on outpatient visits, hospitalisations, surgeries, and drug treatment during 2013 were analysed. A total of 13 916 patients with IBD were identified, corresponding to an overall IBD prevalence of 0.65% [CD 0.27%, UC 0.35%, inflammatory bowel disease unclassified 0.04%]; 49% of all IBD patients were treated with IBD-related drugs. Only 3.6% of the patients received high-dose corticosteroids, whereas 32.4% were treated with aminosalicylates [CD 21.2%, UC 41.0%, p < 0.0001]. More CD patients were treated with biologicals compared with UC patients [CD 9.6%, UC 2.9%, p < 0.0001] and surgery was significantly more common among CD patients [CD 3.0%, UC 0.8%, p < 0.0001]. This study indicates that patients with CD are the group with the highest medical needs. Patients with CD utilised significantly more healthcare resources [including outpatient visits, hospitalisations, and surgeries] than UC patients. Twice as many CD patients received immunomodulators compared with UC patients and CD patients were treated with biologicals three times more often. These results highlight that CD remains a challenge and further efforts are needed to improve care in these patients.

  • 80.
    Cars, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Wettermark, Bjorn
    Malmstrom, Rickard E.
    Ekeving, Gunnar
    Vikstrom, Bo
    Bergman, Ulf
    Neovius, Martin
    Ringertz, Bo
    Gustafsson, Lars L.
    Extraction of Electronic Health Record Data in a Hospital Setting: Comparison of Automatic and Semi-Automatic Methods Using Anti-TNF Therapy as Model2013In: Basic & Clinical Pharmacology & Toxicology, ISSN 1742-7835, E-ISSN 1742-7843, Vol. 112, no 6, p. 392-400Article in journal (Refereed)
    Abstract [en]

    There is limited experience and methods for extractions of drug therapy data from electronic health records (EHR) in the hospital setting. We have therefore developed and evaluated completeness and consistency of an automatic versus a semi-automatic extraction procedure applied on prescribing and administration of the TNF inhibitor infliximab using a hospital EHR system in Karolinska University Hospital, Sweden. Using two different extraction methods (automatic and semi-automatic), all administered infusions of infliximab between 2007 and 2010 were extracted from a database linked to the EHR system. Extracted data included encrypted personal identity number (PIN), date of birth, sex, time of prescription/administration, healthcare units, prescribed/administered dose and time of admission/discharge. The primary diagnosis (ICD-10) for the treatment with infliximab was extracted by linking infliximab infusions to their corresponding treatment episode. A total of 13,590 infusions of infliximab were administered during the period of 2007 to 2010. Of those were 13,531 (99.6%) possible to link to a corresponding treatment episode, and a primary diagnosis was extracted for 13,530 infusions. Information on encrypted PIN, date of birth, time of prescription/administration, time of admission/discharge and healthcare unit was complete. Information about sex was missing in one patient only. Calculable information about dosage was extracted for 13,300 (98.3%) of all linked infusions. This methodological study showed the potential to extract drug therapy data in a hospital setting. The semi-automatic procedure produced an almost complete pattern of demographics, diagnoses and dosages for the treatment with infliximab.

  • 81.
    Cars, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Wettermark, Björn
    Ekeving, Gunnar
    Vikström, Bo
    Malmström, Rickard
    Gustafsson, Lars L.
    Bergman, Ulf
    Neovius, Martin
    Ringertz, Bo
    Extraction of Electronic Health Record Data in a Hospital Setting: Comparison of Automatic and Semi-Automatic Methods Using Anti-TNF Therapy as Model2012In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 21, no SI:3, p. 175-176Article in journal (Other academic)
  • 82.
    Chen, Xu
    et al.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Nobels Vag 12A,POB 281, SE-17177 Stockholm, Sweden.
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Whitington, Thomas
    Karolinska Inst, Dept Med Epidemiol & Biostat, Nobels Vag 12A,POB 281, SE-17177 Stockholm, Sweden.
    Borne, Yan
    Lund Univ, Dept Clin Sci, Malmo, Sweden.
    Lorentzen, Erik
    Gothenburg Univ, Dept Bioinformat, Gothenburg, Sweden.
    Sun, Jitong
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Almgren, Peter
    Lund Univ, Dept Clin Sci, Malmo, Sweden.
    Su, Jun
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Karlsson, Robert
    Karolinska Inst, Dept Med Epidemiol & Biostat, Nobels Vag 12A,POB 281, SE-17177 Stockholm, Sweden.
    Song, Jie
    Karolinska Inst, Dept Med Epidemiol & Biostat, Nobels Vag 12A,POB 281, SE-17177 Stockholm, Sweden.
    Lu, Yi
    Karolinska Inst, Dept Med Epidemiol & Biostat, Nobels Vag 12A,POB 281, SE-17177 Stockholm, Sweden;QIMR Berghofer Med Res Inst, Stat Genet Genet & Computat Biol Dept, Herston, Qld, Australia.
    Zhan, Yiqiang
    Karolinska Inst, Dept Med Epidemiol & Biostat, Nobels Vag 12A,POB 281, SE-17177 Stockholm, Sweden.
    Hagg, Sara
    Karolinska Inst, Dept Med Epidemiol & Biostat, Nobels Vag 12A,POB 281, SE-17177 Stockholm, Sweden.
    Svensson, Per
    Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden;Soder Sjukhuset, Dept Cardiol, Stockholm, Sweden.
    Smedby, Karin E.
    Karolinska Inst, Dept Med, Stockholm, Sweden.
    Slager, Susan L.
    Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med,Cardiovasc Inst, Stanford, CA 94305 USA.
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England;Broad Inst MIT & Harvard Univ, Cambridge, MA USA.
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.
    Melander, Olle
    Lund Univ, Dept Clin Sci, Malmo, Sweden.
    Karlsson, Thomas
    Gothenburg Univ, Sahlgrenska Acad, Inst Med, Hlth Metr, Gothenburg, Sweden.
    de Faire, Ulf
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Caidahl, Kenneth
    Gothenburg Univ, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Engstrom, Gunnar
    Lund Univ, Dept Clin Sci, Malmo, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Karlsson, Mikael C. I.
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden.
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Nobels Vag 12A,POB 281, SE-17177 Stockholm, Sweden.
    Frostegard, Johan
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden;Karolinska Univ Hosp, Dept Emergency Med, Stockholm, Sweden.
    Magnusson, Patrik K. E.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Nobels Vag 12A,POB 281, SE-17177 Stockholm, Sweden.
    A genome-wide association study of IgM antibody against phosphorylcholine: shared genetics and phenotypic relationship to chronic lymphocytic leukemia2018In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 27, no 10, p. 1809-1818Article in journal (Refereed)
    Abstract [en]

    Phosphorylcholine (PC) is an epitope on oxidized low-density lipoprotein (oxLDL), apoptotic cells and several pathogens like Streptococcus pneumoniae. Immunoglobulin M against PC (IgM anti-PC) has the ability to inhibit uptake of oxLDL by macrophages and increase clearance of apoptotic cells. From our genome-wide association studies (GWASs) in four European-ancestry cohorts, six single nucleotide polymorphisms (SNPs) in 11q24.1 were discovered (in 3002 individuals) and replicated (in 646 individuals) to be associated with serum level of IgM anti-PC (the leading SNP rs35923643-G, combined beta = 0.19, 95% confidence interval 0.13-0.24, P = 4.3 x 10(-11)). The haplotype tagged by rs35923643-G (or its proxy SNP rs735665-A) is also known as the top risk allele for chronic lymphocytic leukemia (CLL), and a main increasing allele for general IgM. By using summary GWAS results of IgM anti-PC and CLL in the polygenic risk score (PRS) analysis, PRS on the basis of IgM anti-PC risk alleles positively associated with CLL risk (explained 0.6% of CLL variance, P = 1.2 x 10(-15)). Functional prediction suggested that rs35923643-G might impede the binding of Runt-related transcription factor 3, a tumor suppressor playing a central role in the immune regulation of cancers. Contrary to the expectations from the shared genetics between IgM anti-PC and CLL, an inverse relationship at the phenotypic level was found in a nested case-control study (30 CLL cases with 90 age-and sex-matched controls), potentially reflecting reverse causation. The suggested function of the top variant as well as the phenotypic association between IgM anti-PC and CLL risk needs replication and motivates further studies.

  • 83.
    Chiang, Chern-En
    et al.
    Taipei Vet Gen Hosp, Div Cardiol, Gen Clin Res Ctr, Taipei, Taiwan.;Natl Yang Ming Univ, Taipei 112, Taiwan..
    Ferrieres, Jean
    Toulouse Univ Hosp, Dept Cardiol, Toulouse, France..
    Gotcheva, Nina N.
    Natl Heart Hosp, Dept Cardiol, Sofia, Bulgaria..
    Raal, Frederick J.
    Johannesburg Hosp, Fac Hlth Sci, Johannesburg, South Africa..
    Shehab, Abdulla
    United Arab Emirates Univ, Dept Internal Med, Al Ain, U Arab Emirates..
    Sung, Jidong
    Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea..
    Henriksson, Karin M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. AstraZeneca Gothenburg, Mölndal, Sweden..
    Hermans, Michel P.
    Clin Univ St Luc, Endocrinol & Nutr, B-1200 Brussels, Belgium..
    Suboptimal Control of Lipid Levels: Results from 29 Countries Participating in the Centralized Pan-Regional Surveys on the Undertreatment of Hypercholesterolaemia (CEPHEUS)2016In: Journal of Atherosclerosis and Thrombosis, ISSN 1880-3873, E-ISSN 1340-3478, Vol. 23, no 5, p. 567-587Article in journal (Refereed)
    Abstract [en]

    Aim: Five multicentre, cross-sectional Centralized Pan-Regional Surveys on the Undertreatment of Hypercholesterolaemia (CEPHEUS) were conducted in 29 countries across Asia, Western Europe, Eastern Europe, the Middle East, and Africa. The surveys assessed the current use and efficacy of lipid-lowering drugs (LLDs) worldwide and identified possible patient and physician characteristics associated with failure to attain low-density lipoprotein cholesterol (LDL-C) goals. The aim of this analysis was to consolidate the global results from these surveys. Methods: The surveys involved patients aged >= 18 years who had been prescribed LLDs for at least 3 months without dose changes for at least 6 weeks. A single visit was scheduled for data collection, including fasting plasma lipid and glucose levels. Cardiovascular risk profile and LDL-C goal attainment were assessed according to the 2004 updated US National Cholesterol Education Program Adult Treatment Panel III guidelines. Results: In total, 35 121 patients (mean age: 60.4 years) were included, and 90.3% had been prescribed statin monotherapy. Overall, only 49.4% of patients reached their recommended LDL-C level. LDL-C goals were attained in 54.8% (5084/9273) and 22.8% (3287/14 429) of patients were at high and very high cardiovascular risk, respectively. Factors associated with an increased likelihood of LDL-C goal attainment were lower baseline cardiovascular risk; presence of diabetes mellitus, hypertension, or history of cardiovascular disease; and treatment with simvastatin, atorvastatin, or rosuvastatin (vs. all other LLDs). Conclusion: LDL-C goal attainment in patients taking LLDs is suboptimal worldwide, particularly in patients at high and very high cardiovascular risk.

  • 84.
    Choi, Seung Hoan
    et al.
    Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.;Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA..
    Ruggiero, Daniela
    CNR, Inst Genet & Biophys, Naples, Italy..
    Sorice, Rossella
    CNR, Inst Genet & Biophys, Naples, Italy..
    Song, Ci
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Natl Heart Lung & Blood Inst Framingham Heart Stu, Populat Sci Branch, Framingham, MA USA.;Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Nutile, Teresa
    CNR, Inst Genet & Biophys, Naples, Italy..
    Smith, Albert Vernon
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Reykjavik, Iceland..
    Concas, Maria Pina
    CNR, Inst Populat Genet, Sassari, Italy..
    Traglia, Michela
    Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy..
    Barbieri, Caterina
    Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy..
    Ndiaye, Ndeye Coumba
    Univ Lorraine, Fac Pharm, UMR INSERM U1122, IGE PCV Interact Gene Environm Physiopathol Cardi, Nancy, France..
    Stathopoulou, Maria G.
    Univ Lorraine, Fac Pharm, UMR INSERM U1122, IGE PCV Interact Gene Environm Physiopathol Cardi, Nancy, France..
    Lagou, Vasiliki
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Maestrale, Giovanni Battista
    CNR, Inst Populat Genet, Sassari, Italy..
    Sala, Cinzia
    Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy..
    Debette, Stephanie
    Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.;Bordeaux Univ Hosp, Dept Neurol, Bordeaux, France.;INSERM, U897, Bordeaux, France..
    Kovacs, Peter
    Univ Leipzig, IFB Adipos Dis, D-04109 Leipzig, Germany..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lamont, John
    Randox Labs, Crumlin, Ireland..
    Fitzgerald, Peter
    Randox Labs, Crumlin, Ireland..
    Toenjes, Anke
    Univ Leipzig, Dept Med, D-04109 Leipzig, Germany..
    Gudnason, Vilmundur
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Reykjavik, Iceland..
    Toniolo, Daniela
    Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy..
    Pirastu, Mario
    CNR, Inst Populat Genet, Sassari, Italy..
    Bellenguez, Celine
    Inst Pasteur, F-59019 Lille, France.;INSEM, U744, Lille, France.;Univ Lille Nord France, Lille, France..
    Vasan, Ramachandran S.
    Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA.;Boston Univ, Sch Med, Dept Med, Sect Prevent Med & Epidemiol, Boston, MA 02215 USA.;Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA..
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Leutenegger, Anne-Louise
    INSERM, U946, Paris, France.;Univ Paris Diderot, Sorbonne Paris Cite, IUH, UMR S 946, Paris, France..
    Johnson, Andrew D.
    Natl Heart Lung & Blood Inst Framingham Heart Stu, Populat Sci Branch, Framingham, MA USA..
    DeStefano, Anita L.
    Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.;Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA..
    Visvikis-Siest, Sophie
    Univ Lorraine, Fac Pharm, UMR INSERM U1122, IGE PCV Interact Gene Environm Physiopathol Cardi, Nancy, France..
    Seshadri, Sudha
    Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.;Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA..
    Ciullo, Marina
    CNR, Inst Genet & Biophys, Naples, Italy..
    Six Novel Loci Associated with Circulating VEGF Levels Identified by a Meta-analysis of Genome-Wide Association Studies2016In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 12, no 2, article id e1005874Article in journal (Refereed)
    Abstract [en]

    Vascular endothelial growth factor (VEGF) is an angiogenic and neurotrophic factor, secreted by endothelial cells, known to impact various physiological and disease processes from cancer to cardiovascular disease and to be pharmacologically modifiable. We sought to identify novel loci associated with circulating VEGF levels through a genome-wide association meta-analysis combining data from European-ancestry individuals and using a dense variant map from 1000 genomes imputation panel. Six discovery cohorts including 13,312 samples were analyzed, followed by in-silico and de-novo replication studies including an additional 2,800 individuals. A total of 10 genome-wide significant variants were identified at 7 loci. Four were novel loci (5q14.3, 10q21.3, 16q24.2 and 18q22.3) and the leading variants at these loci were rs114694170 (MEF2C, P = 6.79x10(-13)), rs74506613 (JMJD1C, P = 1.17x10(-19)), rs4782371 (ZFPM1, P = 1.59x10(-9)) and rs2639990 (ZADH2, P = 1.72x10(-8)), respectively. We also identified two new independent variants (rs34528081, VEGFA, P = 1.52x10(-18); rs7043199, VLDLR-AS1, P = 5.12x10(-14)) at the 3 previously identified loci and strengthened the evidence for the four previously identified SNPs (rs6921438, LOC100132354, P = 7.39x10(-1467); rs1740073, C6orf223, P = 2.34x10(-17); rs6993770, ZFPM2, P = 2.44x10(-60); rs2375981, KCNV2, P = 1.48x10(-100)). These variants collectively explained up to 52% of the VEGF phenotypic variance. We explored biological links between genes in the associated loci using Ingenuity Pathway Analysis that emphasized their roles in embryonic development and function. Gene set enrichment analysis identified the ERK5 pathway as enriched in genes containing VEGF associated variants. eQTL analysis showed, in three of the identified regions, variants acting as both cis and trans eQTLs for multiple genes. Most of these genes, as well as some of those in the associated loci, were involved in platelet biogenesis and functionality, suggesting the importance of this process in regulation of VEGF levels. This work also provided new insights into the involvement of genes implicated in various angiogenesis related pathologies in determining circulating VEGF levels. The understanding of the molecular mechanisms by which the identified genes affect circulating VEGF levels could be important in the development of novel VEGF-related therapies for such diseases.

    Download full text (pdf)
    fulltext
  • 85.
    Christophersen, Ingrid E.
    et al.
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Vestre Viken Hosp Trust, Baerum Hosp, Dept Med Res, Rud, Norway..
    Rienstra, Michiel
    Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, Groningen, Netherlands..
    Roselli, Carolina
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany..
    Yin, Xiaoyan
    NHLBI, Framingham, MA USA.;Boston Univ Framingham Heart Study, Framingham, MA USA.;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA..
    Geelhoed, Bastiaan
    Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, Groningen, Netherlands..
    Barnard, John
    Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Cellular & Mol Med, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Mol Cardiol, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA..
    Lin, Honghuang
    NHLBI, Framingham, MA USA.;Boston Univ Framingham Heart Study, Framingham, MA USA.;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA..
    Arking, Dan E.
    Johns Hopkins Univ Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA..
    Smith, Albert V.
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Albert, Christine M.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA..
    Chaffin, Mark
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA..
    Tucker, Nathan R.
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA..
    Li, Molong
    Klarin, Derek
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA..
    Bihlmeyer, Nathan A.
    Johns Hopkins Univ Sch Med, McKusick Nathans Inst Genet Med, Predoctoral Training Program Human Genet, Baltimore, MD USA..
    Low, Siew-Kee
    RIKEN, Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan..
    Weeke, Peter E.
    Vanderbilt Univ, Med Ctr, Dept Med, 221 Kirkland Hall, Nashville, TN 37235 USA.;Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Heart Ctr, Copenhagen, Denmark..
    Mueller-Nurasyid, Martina
    Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, Neuherberg, Germany.;Univ Hosp Munich, Ludwig Maximilians Univ, Dept Med 1, Munich, Germany.;DZHK German Ctr Cardiovasc Res, Munich Heart Alliance, Munich, Germany..
    Smith, J. Gustav
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Lund Univ, Clin Sci, Molecular Epidemiol & Cardiol, Lund, Sweden..
    Brody, Jennifer A.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA..
    Niemeijer, Maartje N.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Doerr, Marcus
    Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany.;DZHK German Ctr Cardiovasc Res, Greifswald, Germany..
    Trompet, Stella
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands..
    Huffman, Jennifer
    Univ Edinburgh, Inst Genet & Mol Med, MRC, Human Genet Unit, Edinburgh, Midlothian, Scotland..
    Gustafsson, Stefan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Schurmann, Claudia
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA..
    Kleber, Marcus E.
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Heidelberg, Germany..
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Tampere, Finland..
    Seppala, Ilkka
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Tampere, Finland..
    Malik, Rainer
    Klinikum Univ Munchen, Inst Stroke & Dementia Res, Ludwig Maximilians Univ, Munich, Germany..
    Horimoto, Andrea R. V. R.
    Univ Sao Paulo, Heart Inst, Lab Genet & Mol Cardiol, Sao Paulo, Brazil..
    Perez, Marco
    Stanford Univ, Dept Cardiovasc Med, Stanford, CA 94305 USA..
    Sinisalo, Juha
    Univ Helsinki, Cent Hosp, Heart & Lung Ctr HUS, Helsinki, Finland..
    Aeschbacher, Stefanie
    Univ Basel Hosp, Dept Med, Basel, Switzerland.;Cardiovasc Res Inst Basel, Basel, Switzerland..
    Theriault, Sebastien
    Populat Hlth Res Inst, Hamilton, ON, Canada.;McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada..
    Yao, Jie
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA..
    Radmanesh, Farid
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA..
    Weiss, Stefan
    DZHK German Ctr Cardiovasc Res, Greifswald, Germany.;Univ Med, Interfac Inst Genet & Funct Gen, Greifswald, Germany.;Ernst Moritz Arndt Univ Greifswald, Greifswald, Germany..
    Teumer, Alexander
    DZHK German Ctr Cardiovasc Res, Greifswald, Germany.;Univ Med Greifswald, Inst Community Med, Greifswald, Germany..
    Choi, Seung Hoan
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA..
    Weng, Lu-Chen
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA..
    Clauss, Sebastian
    Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Univ Hosp Munich, Ludwig Maximilians Univ, Dept Med 1, Munich, Germany.;DZHK German Ctr Cardiovasc Res, Munich Heart Alliance, Munich, Germany..
    Deo, Rajat
    Univ Penn, Perelman Sch Med, Dept Med, Div Cardiovasc Med, Philadelphia, PA 19104 USA..
    Rader, Daniel J.
    Univ Penn, Perelman Sch Med, Dept Med, Div Cardiovasc Med, Philadelphia, PA 19104 USA..
    Shah, Svati H.
    Duke Univ, Sch Med, Dept Med, Div Cardiol, Durham, NC 27706 USA..
    Sun, Albert
    Duke Univ, Sch Med, Dept Med, Div Cardiol, Durham, NC 27706 USA..
    Hopewell, Jemma C.
    Univ Oxford, CTSU Nuffield Dept Populat Hlth, Oxford, England..
    Debette, Stephanie
    Bordeaux Populat Hlth Ctr, INSERM U1219, Bordeaux, France.;Univ Bordeaux, Bordeaux, France.;Bordeaux Univ Hosp, Dept Neurol, Bordeaux, France.;Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA..
    Chauhan, Ganesh
    Bordeaux Populat Hlth Ctr, INSERM U1219, Bordeaux, France.;Univ Bordeaux, Bordeaux, France..
    Yang, Qiong
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA..
    Worrall, Bradford B.
    Univ Virginia Hlth Syst, Dept Neurol, Charlottesville, VA USA.;Univ Virginia Hlth Syst, Dept Publ Hlth Sci, Charlottesville, VA USA..
    Pare, Guillaume
    Populat Hlth Res Inst, Hamilton, ON, Canada.;McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada..
    Kamatani, Yoichiro
    RIKEN, Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan..
    Hagemeijer, Yanick P.
    Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, Groningen, Netherlands..
    Verweij, Niek
    Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, Groningen, Netherlands..
    Siland, Joylene E.
    Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, Groningen, Netherlands..
    Kubo, Michiaki
    RIKEN, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan..
    Smith, Jonathan D.
    Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Cellular & Mol Med, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Mol Cardiol, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA..
    Van Wagoner, David R.
    Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Cellular & Mol Med, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Mol Cardiol, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA..
    Bis, Joshua C.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA..
    Perz, Siegfried
    Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, Neuherberg, Germany..
    Psaty, Bruce M.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.;Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.;Univ Washington, Cardiovasc Hlth Res Unit, Washington, DC USA.;Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.;Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA..
    Ridker, Paul M.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA..
    Magnani, Jared W.
    NHLBI, Framingham, MA USA.;Boston Univ Framingham Heart Study, Framingham, MA USA.;Boston Univ, Sch Med, Dept Med, Boston, MA 02215 USA..
    Harris, Tamara B.
    Natl Inst Aging, Lab Epidemiol Demog & Biometry, Bethesda, MD USA..
    Launer, Lenore J.
    Natl Inst Aging, Lab Epidemiol Demog & Biometry, Bethesda, MD USA..
    Shoemaker, M. Benjamin
    Vanderbilt Univ, Med Ctr, Dept Med, 221 Kirkland Hall, Nashville, TN 37235 USA..
    Padmanabhan, Sandosh
    Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland..
    Haessler, Jeffrey
    Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA..
    Bartz, Traci M.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.;Univ Washington, Dept Biostat, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA..
    Waldenberger, Melanie
    DZHK German Ctr Cardiovasc Res, Munich Heart Alliance, Munich, Germany.;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, Neuherberg, Germany.;Helmholtz Zentrum Munchen German Res Ctr Environm, Res Unit Mol Epidemiol, Neuherberg, Germany..
    Lichtner, Peter
    Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Human Genet, Neuherberg, Germany..
    Arendt, Marina
    Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany..
    Krieger, Jose E.
    Univ Sao Paulo, Heart Inst, Lab Genet & Mol Cardiol, Sao Paulo, Brazil..
    Kahonen, Mika
    Univ Tampere, Sch Med, Tampere, Finland.;Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland..
    Risch, Lorenz
    Univ Bern, Univ Inst Clin Chem, Bern, Switzerland.;Labormed Zentrum Dr Risch, Schaan, Liechtenstein..
    Mansur, Alfredo J.
    Univ Sao Paulo, Heart Inst, Sao Paulo, Brazil..
    Peters, Annette
    DZHK German Ctr Cardiovasc Res, Munich Heart Alliance, Munich, Germany.;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, Neuherberg, Germany.;German Ctr Diabet Res, Neuherberg, Germany..
    Smith, Blair H.
    Univ Dundee, Div Populat Hlth Sci, Dundee, Scotland..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Scott, Stuart A.
    Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA..
    Lu, Yingchang
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA..
    Bottinger, Erwin B.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA..
    Hernesniemi, Jussi
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Tampere, Finland.;Tampere Univ Hosp, Heart Hosp, Dept Cardiol, Tampere, Finland..
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Wong, Jorge A.
    McMaster Univ, Div Cardiol Hamilton Hlth Sci, Hamilton, ON, Canada..
    Huang, Jie
    Boston VA Res Inst Inc, Boston, MA USA..
    Eskola, Markku
    Univ Tampere, Sch Med, Tampere, Finland.;Tampere Univ Hosp, Heart Hosp, Dept Cardiol, Tampere, Finland..
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    Ford, Ian
    Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland..
    Reiner, Alex P.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.;Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland..
    Delgado, Graciela
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Heidelberg, Germany..
    Chen, Lin Y.
    Univ Minnesota, Dept Med, Med Sch, Cardiovasc Div, Box 736 UMHC, Minneapolis, MN 55455 USA..
    Chen, Yii-Der Ida
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA..
    Sandhu, Roopinder K.
    Univ Alberta, Div Cardiol, Edmonton, AB, Canada..
    Li, Man
    Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.;Univ Utah, Sch Med, Div Nephrol & Hypertens, Internal Med, Salt Lake City, UT USA..
    Boerwinkle, Eric
    Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA..
    Eisele, Lewin
    Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany..
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Rost, Natalia
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Acute Stroke Serv, Boston, MA 02114 USA..
    Anderson, Christopher D.
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA..
    Taylor, Kent D.
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA..
    Campbell, Archie
    Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Generat Scotland, Edinburgh, Midlothian, Scotland..
    Magnusson, Patrik K.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Porteous, David
    Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Generat Scotland, Edinburgh, Midlothian, Scotland..
    Hocking, Lynne J.
    Univ Aberdeen, Div Appl Med, Musculoskeletal Res Programme, Aberdeen, Scotland..
    Vlachopoulou, Efthymia
    Univ Helsinki, Medicum, Transplantat Lab, Helsinki, Finland..
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Nikus, Kjell
    Univ Tampere, Sch Med, Tampere, Finland.;Tampere Univ Hosp, Heart Hosp, Dept Cardiol, Tampere, Finland..
    Orho-Melander, Marju
    Lund Univ, Dept Clin Sci, Malmo, Sweden..
    Hamsten, Anders
    Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Cardiovasc Genet & Genom Grp, Stockholm, Sweden..
    Heeringa, Jan
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Denny, Joshua C.
    Vanderbilt Univ, Med Ctr, Dept Med, 221 Kirkland Hall, Nashville, TN 37235 USA..
    Kriebel, Jennifer
    Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, Neuherberg, Germany.;Helmholtz Zentrum Munchen German Res Ctr Environm, Res Unit Mol Epidemiol, Neuherberg, Germany.;German Ctr Diabet Res, Neuherberg, Germany..
    Darbar, Dawood
    Univ Illinois, Dept Med & Pharmacol, Chicago, IL USA..
    Newton-Cheh, Christopher
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA..
    Shaffer, Christian
    Vanderbilt Univ, Med Ctr, Dept Med, 221 Kirkland Hall, Nashville, TN 37235 USA..
    Macfarlane, Peter W.
    Univ Glasgow, Coll Med Vet & Sci, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland..
    Heilmann-Heimbach, Stefanie
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Univ Bonn, Life & Brain Res Ctr, Dept Gen, Bonn, Germany..
    Almgren, Peter
    Lund Univ, Dept Clin Sci, Malmo, Sweden..
    Huang, Paul L.
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA..
    Sotoodehnia, Nona
    Univ Washington, Cardiovasc Hlth Res Unit, Washington, DC USA..
    Soliman, Elsayed Z.
    Wake Forest Sch Med, Epidemiol Cardiol Res Ctr EPICARE, Winston Salem, NC USA..
    Uitterlinden, Andre G.
    Erasmus MC, Dept Epidemiol & Internal Med, Rotterdam, Netherlands..
    Hofman, Albert
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Franco, Oscar H.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Voelker, Uwe
    DZHK German Ctr Cardiovasc Res, Greifswald, Germany.;Univ Med, Interfac Inst Genet & Funct Gen, Greifswald, Germany.;Ernst Moritz Arndt Univ Greifswald, Greifswald, Germany..
    Joeckel, Karl-Heinz
    Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany..
    Sinner, Moritz F.
    Univ Hosp Munich, Ludwig Maximilians Univ, Dept Med 1, Munich, Germany.;DZHK German Ctr Cardiovasc Res, Munich Heart Alliance, Munich, Germany..
    Lin, Henry J.
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA..
    Guo, Xiuqing
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA..
    Dichgans, Martin
    Klinikum Univ Munchen, Inst Stroke & Dementia Res, Ludwig Maximilians Univ, Munich, Germany.;Munich Cluster Syst Neurol SyNergy, Munich, Germany.;German Ctr Neurodegenerat Dis DZNE, Munich, Germany..
    Ingelsson, Erik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Kooperberg, Charles
    Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA..
    Melander, Olle
    Lund Univ, Clin Sci, Dept Internal Med, Malmo, Sweden..
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA..
    Laurikka, Jari
    Univ Tampere, Sch Med, Tampere, Finland.;Tampere Univ Hosp, Heart Hosp, Dept Cardio Thorac Surg, Tampere, Finland..
    Conen, David
    Univ Basel Hosp, Dept Med, Basel, Switzerland.;Cardiovasc Res Inst Basel, Basel, Switzerland..
    Rosand, Jonathan
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA..
    van der Harst, Pim
    Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, Groningen, Netherlands..
    Lokki, Marja-Liisa
    Univ Helsinki, Medicum, Transplantat Lab, Helsinki, Finland..
    Kathiresan, Sekar
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA..
    Pereira, Alexandre
    Univ Sao Paulo, Heart Inst, Lab Genet & Mol Cardiol, Sao Paulo, Brazil.;Harvard Med Sch, Dept Genet, Boston, MA USA..
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.;Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands.;Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands..
    Hayward, Caroline
    Univ Edinburgh, Inst Genet & Mol Med, MRC, Human Genet Unit, Edinburgh, Midlothian, Scotland..
    Rotter, Jerome I.
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.;Harbor UCLA Med Ctr, LABioMed, Dept Med, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA..
    Maerz, Winfried
    Med Univ Graz, Inst Clin Med, Graz, Austria.;Med Univ Graz, Chem Lab Diagnost, Graz, Austria.;Synlab Holding Deutschland GmbH, Synlab Acad, Mannheim, Germany.;Synlab Holding Deutschland GmbH, Synlab Acad, Augsburg, Germany..
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Tampere, Finland..
    Stricker, Bruno H.
    Erasmus MC, Dept Epidemiol & Internal Med, Rotterdam, Netherlands.;Inspectorate Hlth Care, Utrecht, Netherlands..
    Chung, Mina K.
    Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Cellular & Mol Med, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Mol Cardiol, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA..
    Felix, Stephan B.
    Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany.;DZHK German Ctr Cardiovasc Res, Greifswald, Germany..
    Gudnason, Vilmundur
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Alonso, Alvaro
    Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA..
    Roden, Dan M.
    Vanderbilt Univ, Med Ctr, Dept Med, 221 Kirkland Hall, Nashville, TN 37235 USA..
    Kaeaeb, Stefan
    Univ Hosp Munich, Ludwig Maximilians Univ, Dept Med 1, Munich, Germany.;DZHK German Ctr Cardiovasc Res, Munich Heart Alliance, Munich, Germany..
    Chasman, Daniel I.
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Genet, 75 Francis St, Boston, MA 02115 USA..
    Heckbert, Susan R.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.;Univ Washington, Cardiovasc Hlth Res Unit, Washington, DC USA.;Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA..
    Benjamin, Emelia J.
    NHLBI, Framingham, MA USA.;Boston Univ Framingham Heart Study, Framingham, MA USA.;Boston Univ, Sch Med, Dept Med, Boston, MA 02215 USA.;Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA..
    Tanaka, Toshihiro
    RIKEN, Ctr Integrat Med Sci, Lab Cardiovasc Dis, Yokohama, Kanagawa, Japan.;Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Human Genet & Dis Divers, Tokyo, Japan..
    Lunetta, Kathryn L.
    NHLBI, Framingham, MA USA.;Boston Univ Framingham Heart Study, Framingham, MA USA..
    Lubitz, Steven A.
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA..
    Ellinor, Patrick T.
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA..
    Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation2017In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 49, no 6, p. 946-+Article in journal (Refereed)
    Abstract [en]

    Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death(1,2). Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups(3-7). To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 17,931 individuals with atrial fibrillation and 115,142 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases and 132,086 referents. We identified 12 new genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate the identification of new potential targets for drug discovery(8).

  • 86. Conen, David
    et al.
    Aeschbacher, Stefanie
    Thijs, Lutgarde
    Li, Yan
    Boggia, Jose
    Asayama, Kei
    Hansen, Tine W.
    Kikuya, Masahiro
    Bjorklund-Bodegard, Krishna
    Ohkubo, Takayoshi
    Jeppesen, Jorgen
    Gu, Yu-Mei
    Torp-Pedersen, Christian
    Dolan, Eamon
    Kuznetsova, Tatiana
    Stolarz-Skrzypek, Katarzyna
    Tikhonoff, Valerie
    Schoen, Tobias
    Malyutina, Sofia
    Casiglia, Edoardo
    Nikitin, Yuri
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sandoya, Edgardo
    Kawecka-Jaszcz, Kalina
    Mena, Luis
    Maestre, Gladys E.
    Filipovsky, Jan
    Imai, Yutaka
    O'Brien, Eoin
    Wang, Ji-Guang
    Risch, Lorenz
    Staessen, Jan A.
    Age-Specific Differences Between Conventional and Ambulatory Daytime Blood Pressure Values2014In: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 64, no 5, p. 1073-1079Article in journal (Refereed)
    Abstract [en]

    Mean daytime ambulatory blood pressure (BP) values are considered to be lower than conventional BP values, but data on this relation among younger individuals <50 years are scarce. Conventional and 24-hour ambulatory BP were measured in 9550 individuals not taking antihypertensive treatment from 13 population-based cohorts. We compared individual differences between daytime ambulatory and conventional BP according to 10-year age categories. Age-specific prevalences of white coat and masked hypertension were calculated. Among individuals aged 18 to 30, 30 to 40, and 40 to 50 years, mean daytime BP was significantly higher than the corresponding conventional BP (6.0, 5.2, and 4.7 mm Hg for systolic; 2.5, 2.7, and 1.7 mm Hg for diastolic BP; all P<0.0001). In individuals aged 60 to 70 and >= 70 years, conventional BP was significantly higher than daytime ambulatory BP (5.0 and 13.0 mm Hg for systolic; 2.0 and 4.2 mm Hg for diastolic BP; all P<0.0001). The prevalence of white coat hypertension exponentially increased from 2.2% to 19.5% from those aged 18 to 30 years to those aged >= 70 years, with little variation between men and women (8.0% versus 6.1%; P=0.0003). Masked hypertension was more prevalent among men (21.1% versus 11.4%; P<0.0001). The age-specific prevalences of masked hypertension were 18.2%, 27.3%, 27.8%, 20.1%, 13.6%, and 10.2% among men and 9.0%, 9.9%, 12.2%, 11.9%, 14.7%, and 12.1% among women. In conclusion, this large collaborative analysis showed that the relation between daytime ambulatory and conventional BP strongly varies by age. These findings may have implications for diagnosing hypertension and its subtypes in clinical practice.

  • 87. Cornelis, M C
    et al.
    Byrne, E M
    Esko, T
    Nalls, M A
    Ganna, A
    Paynter, N
    Monda, K L
    Amin, N
    Fischer, K
    Renstrom, F
    Ngwa, J S
    Huikari, V
    Cavadino, A
    Nolte, I M
    Teumer, A
    Yu, K
    Marques-Vidal, P
    Rawal, R
    Manichaikul, A
    Wojczynski, M K
    Vink, J M
    Zhao, J H
    Burlutsky, G
    Lahti, J
    Mikkilä, V
    Lemaitre, R N
    Eriksson, J
    Musani, S K
    Tanaka, T
    Geller, F
    Luan, J
    Hui, J
    Mägi, R
    Dimitriou, M
    Garcia, M E
    Ho, W-K
    Wright, M J
    Rose, L M
    Magnusson, P K E
    Pedersen, N L
    Couper, D
    Oostra, B A
    Hofman, A
    Ikram, M A
    Tiemeier, H W
    Uitterlinden, A G
    van Rooij, F J A
    Barroso, I
    Johansson, I
    Xue, L
    Kaakinen, M
    Milani, L
    Power, C
    Snieder, H
    Stolk, R P
    Baumeister, S E
    Biffar, R
    Gu, F
    Bastardot, F
    Kutalik, Z
    Jacobs, D R
    Forouhi, N G
    Mihailov, E
    Lind, Lars
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lindgren, C
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Morris, A
    Jensen, M
    Khaw, K-T
    Luben, R N
    Wang, J J
    Männistö, S
    Perälä, M-M
    Kähönen, M
    Lehtimäki, T
    Viikari, J
    Mozaffarian, D
    Mukamal, K
    Psaty, B M
    Döring, A
    Heath, A C
    Montgomery, G W
    Dahmen, N
    Carithers, T
    Tucker, K L
    Ferrucci, L
    Boyd, H A
    Melbye, M
    Treur, J L
    Mellström, D
    Hottenga, J J
    Prokopenko, I
    Tönjes, A
    Deloukas, P
    Kanoni, S
    Lorentzon, M
    Houston, D K
    Liu, Y
    Danesh, J
    Rasheed, A
    Mason, M A
    Zonderman, A B
    Franke, L
    Kristal, B S
    Karjalainen, J
    Reed, D R
    Westra, H-J
    Evans, M K
    Saleheen, D
    Harris, T B
    Dedoussis, G
    Curhan, G
    Stumvoll, M
    Beilby, J
    Pasquale, L R
    Feenstra, B
    Bandinelli, S
    Ordovas, J M
    Chan, A T
    Peters, U
    Ohlsson, C
    Gieger, C
    Martin, N G
    Waldenberger, M
    Siscovick, D S
    Raitakari, O
    Eriksson, J G
    Mitchell, P
    Hunter, D J
    Kraft, P
    Rimm, E B
    Boomsma, D I
    Borecki, I B
    Loos, R J F
    Wareham, N J
    Vollenweider, P
    Caporaso, N
    Grabe, H J
    Neuhouser, M L
    Wolffenbuttel, B H R
    Hu, F B
    Hyppönen, E
    Järvelin, M-R
    Cupples, L A
    Franks, P W
    Ridker, P M
    van Duijn, C M
    Heiss, G
    Metspalu, A
    North, K E
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nettleton, J A
    van Dam, R M
    Chasman, D I
    Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption2015In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 20, no 5, p. 647-656Article in journal (Refereed)
    Abstract [en]

    Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91 462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)>5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P<5 × 10(-8)).Our genetic findings among European and African-American adults reinforce the role of caffeine in mediating habitual coffee consumption and may point to molecular mechanisms underlying inter-individual variability in pharmacological and health effects of coffee.

  • 88. Cornelis, M C
    et al.
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ärnlöv, J
    Elmståhl, S
    Söderberg, S
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
    Targeted proteomic analysis of habitual coffee consumption.2018In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 283, no 2, p. 200-211Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Coffee drinking has been implicated in mortality and a variety of diseases but potential mechanisms underlying these associations are unclear. Large-scale systems epidemiological approaches may offer novel insights to mechanisms underlying associations of coffee with health.

    OBJECTIVE: We performed an analysis of known and novel protein markers linked to cardiovascular disease and their association with habitual coffee intake in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS, n = 816) and followed up top proteins in the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 635) and EpiHealth (n = 2418).

    METHODS: In PIVUS and ULSAM, coffee intake was measured by 7-day dietary records whilst a computer-based food frequency questionnaire was used in EpiHealth. Levels of up to 80 proteins were assessed in plasma by a proximity extension assay.

    RESULTS: Four protein-coffee associations adjusted for age, sex, smoking and BMI, met statistical significance in PIVUS (FDR < 5%, P < 2.31 × 10(-3) ): leptin (LEP), chitinase-3-like protein 1 (CHI3L), tumour necrosis factor (TNF) receptor 6 and TNF-related apoptosis-inducing ligand. The inverse association between coffee intake and LEP replicated in ULSAM (β, -0.042 SD per cup of coffee, P = 0.028) and EpiHealth (β, -0.025 SD per time of coffee, P = 0.004). The negative coffee-CHI3L association replicated in EpiHealth (β, -0.07, P = 1.15 × 10(-7) ), but not in ULSAM (β, -0.034, P = 0.16).

    CONCLUSIONS: The current study supports an inverse association between coffee intake and plasma LEP and CHI3L1 levels. The coffee-CHI3L1 association is novel and warrants further investigation given links between CHI3L1 and health conditions that are also potentially influenced by coffee.

  • 89. Cornelis, Marilyn C
    et al.
    Kacprowski, Tim
    Menni, Cristina
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pivin, Edward
    Adamski, Jerzy
    Artati, Anna
    Eap, Chin B
    Ehret, Georg
    Friedrich, Nele
    Ganna, Andrea
    Guessous, Idris
    Homuth, Georg
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Magnusson, Patrik K
    Mangino, Massimo
    Pedersen, Nancy L
    Pietzner, Maik
    Suhre, Karsten
    Völzke, Henry
    Bochud, Murielle
    Spector, Tim D
    Grabe, Hans J
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, USA..
    Genome-wide association study of caffeine metabolites provides new insights to caffeine metabolism and dietary caffeine-consumption behavior2016In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 25, no 24, p. 5472-5482Article in journal (Refereed)
    Abstract [en]

    Caffeine is the most widely consumed psychoactive substance in the world and presents with wide interindividual variation in metabolism. This variation may modify potential adverse or beneficial effects of caffeine on health. We conducted a genome-wide association study (GWAS) of plasma caffeine, paraxanthine, theophylline, theobromine and paraxanthine/caffeine ratio among up to 9,876 individuals of European ancestry from six population-based studies. A single SNP at 6p23 (near CD83) and several SNPs at 7p21 (near AHR), 15q24 (near CYP1A2) and 19q13.2 (near CYP2A6) met GW-significance (P < 5 × 10(-8)) and were associated with one or more metabolites. Variants at 7p21 and 15q24 associated with higher plasma caffeine and lower plasma paraxanthine/caffeine (slow caffeine metabolism) were previously associated with lower coffee and caffeine consumption behavior in GWAS. Variants at 19q13.2 associated with higher plasma paraxanthine/caffeine (slow paraxanthine metabolism) were also associated with lower coffee consumption in the UK Biobank (n = 94 343, P < 1.0 × 10(-6)). Variants at 2p24 (in GCKR), 4q22 (in ABCG2) and 7q11.23 (near POR) that were previously associated with coffee consumption in GWAS were nominally associated with plasma caffeine or its metabolites. Taken together, we have identified genetic factors contributing to variation in caffeine metabolism and confirm an important modulating role of systemic caffeine levels in dietary caffeine consumption behavior. Moreover, candidate genes identified encode proteins with important clinical functions that extend beyond caffeine metabolism.

  • 90. Danaei, Goodarz
    et al.
    Fahimi, Saman
    Lu, Yuan
    Zhou, Bin
    Hajifathalian, Kaveh
    Di Cesare, Mariachiara
    Lo, Wei-Cheng
    Reis-Santos, Barbara
    Cowan, Melanie J.
    Shaw, Jonathan E.
    Bentham, James
    Lin, John K.
    Bixby, Honor
    Magliano, Dianna
    Bovet, Pascal
    Miranda, J. Jaime
    Khang, Young-Ho
    Stevens, Gretchen A.
    Riley, Leanne M.
    Ali, Mohammed K.
    Ezzati, Majid
    Abdeen, Ziad A.
    Kadir, Khalid Abdul
    Abu-Rmeileh, Niveen M.
    Acosta-Cazares, Benjamin
    Aekplakorn, Wichai
    Aguilar-Salinas, Carlos A.
    Ahmadvand, Alireza
    Al Nsour, Mohannad
    Alkerwi, Ala'a
    Amouyel, Philippe
    Andersen, Lars Bo
    Anderssen, Sigmund A.
    Andrade, Dolores S.
    Anjana, Ranjit Mohan
    Aounallah-Skhiri, Hajer
    Aris, Tahir
    Arlappa, Nimmathota
    Arveiler, Dominique
    Assah, Felix K.
    Avdicova, Maria
    Balakrishna, Nagalla
    Bandosz, Piotr
    Barbagallo, Carlo M.
    Barcelo, Alberto
    Batieha, Anwar M.
    Baur, Louise A.
    Ben Romdhane, Habiba
    Bernabe-Ortiz, Antonio
    Bhargava, Santosh K.
    Bi, Yufang
    Bjerregaard, Peter
    Bjorkelund, Cecilia
    Blake, Margaret
    Blokstra, Anneke
    Bo, Simona
    Boehm, Bernhard O.
    Boissonnet, Carlos P.
    Brajkovich, Imperia
    Breckenkamp, Juergen
    Brewster, Lizzy M.
    Brian, Garry R.
    Bruno, Graziella
    Bugge, Anna
    de Leon, Antonio Cabrera
    Can, Gunay
    Candido, Ana Paula C.
    Capuano, Vincenzo
    Carvalho, Maria J.
    Casanueva, Felipe F.
    Caserta, Carmelo A.
    Castetbon, Katia
    Chamukuttan, Snehalatha
    Chaturvedi, Nishi
    Chen, Chien-Jen
    Chen, Fangfang
    Chen, Shuohua
    Cheng, Ching-Yu
    Chetrit, Angela
    Chiou, Shu-Ti
    Cho, Yumi
    Chudek, Jerzy
    Cifkova, Renata
    Claessens, Frank
    Concin, Hans
    Cooper, Cyrus
    Cooper, Rachel
    Costanzo, Simona
    Cottel, Dominique
    Cowell, Chris
    Crujeiras, Ana B.
    D'Arrigo, Graziella
    Dallongeville, Jean
    Dankner, Rachel
    Dauchet, Luc
    de Gaetano, Giovanni
    De Henauw, Stefaan
    Deepa, Mohan
    Dehghan, Abbas
    Dhana, Klodian
    Di Castelnuovo, Augusto F.
    Djalalinia, Shirin
    Doua, Kouamelan
    Drygas, Wojciech
    Du, Yong
    Egbagbe, Eruke E.
    Eggertsen, Robert
    El Ati, Jalila
    Elosua, Roberto
    Erasmus, Rajiv T.
    Erem, Cihangir
    Ergor, Gul
    Eriksen, Louise
    la Penaa, Jorge Escobedo-De
    Fall, Caroline H.
    Farzadfar, Farshad
    Felix-Redondo, Francisco J.
    Ferguson, Trevor S.
    Fernandez-Berges, Daniel
    Ferrari, Marika
    Ferreccio, Catterina
    Finn, Joseph D.
    Foger, Bernhard
    Foo, Leng Huat
    Fouad, Heba M.
    Francis, Damian K.
    Franco, Maria do Carmo
    Franco, Oscar H.
    Frontera, Guillermo
    Furusawa, Takuro
    Gaciong, Zbigniew
    Galbarczyk, Andrzej
    Garnett, Sarah P.
    Gaspoz, Jean-Michel
    Gasull, Magda
    Gates, Louise
    Geleijnse, Johanna M.
    Ghasemain, Anoosheh
    Giampaoli, Simona
    Gianfagna, Francesco
    Giovannelli, Jonathan
    Gross, Marcela Gonzalez
    Rivas, Juan P. Gonzalez
    Gorbea, Mariano Bonet
    Gottrand, Frederic
    Grant, Janet F.
    Grodzicki, Tomasz
    Grontved, Anders
    Gruden, Grabriella
    Gu, Dongfeng
    Guan, Ong Peng
    Guerrero, Ramiro
    Guessous, Idris
    Guimaraes, Andre L.
    Gutierrez, Laura
    Hardy, Rebecca
    Kumar, Rachakulla Hari
    He, Jiang
    Heidemann, Christin
    Hihtaniemi, Ilpo Tapani
    Ho, Sai Yin
    Ho, Suzanne C.
    Hofman, Albert
    Russo, Andrea R. V.
    Hormiga, Claudia M.
    Horta, Bernardo L.
    Houti, Leila
    Hussieni, Abdullatif S.
    Huybrechts, Inge
    Hwalla, Nahla
    Iacoviello, Licia
    Iannone, Anna G.
    Ibrahim, Mohsen M.
    Ikeda, Nayu
    Ikram, M. Arfan
    Irazola, Vilma E.
    Islam, Muhammad
    Iwasaki, Masanori
    Jacobs, Jeremy M.
    Jafar, Tazeen
    Jasienska, Grazyna
    Jiang, Chao Qiang
    Jonas, Jost B.
    Joshi, Pradeep
    Kafatos, Anthony
    Kalter-Leibovici, Ofra
    Kasaeian, Amir
    Katz, Joanne
    Kaur, Prabhdeep
    Kavousi, Maryam
    Kelishadi, Roya
    Kengne, Andre P.
    Kersting, Mathilde
    Khader, Yousef Saleh
    Kiechl, Stefan
    Kim, Jeongseon
    Kiyohara, Yutaka
    Kolsteren, Patrick
    Korrovits, Paul
    Koskinen, Seppo
    Kratzer, Wolfgang
    Kromhout, Daan
    Kula, Krzysztof
    Kurjata, Pawel
    Kyobutungi, Catherine
    Lachat, Carl
    Laid, Youcef
    Lam, Tai Hing
    Landrove, Orlando
    Lanska, Vera
    Lappas, Georg
    Laxmaiah, Avula
    Leclercq, Catherine
    Lee, Jeannette
    Lee, Jeonghee
    Lehtimaki, Terho
    Lekhraj, Rampal
    Leon-Munoz, Luz M.
    Li, Yanping
    Lim, Wei-Yen
    Lima-Costa, M. Fernanda
    Lin, Hsien-Ho
    Lin, Xu
    Lissner, Lauren
    Lorbeer, Roberto
    Lozano, Jose Eugenio
    Lundqvist, Annamari
    Lytsy, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Ma, Guansheng
    Machado-Coelho, George L. L.
    Machi, Suka
    Maggi, Stefania
    Makdisse, Marcia
    Rao, Kodavanti Mallikharjuna
    Manios, Yannis
    Manzato, Enzo
    Margozzini, Paula
    Marques-Vidal, Pedro
    Martorell, Reynaldo
    Masoodi, Shariq R.
    Matsha, Tandi E.
    Mbanya, Jean Claude N.
    McFarlane, Shelly R.
    McGarvey, Stephen T.
    McLachlan, Stela
    McNulty, Breige A.
    Mediene-Benchekor, Sounnia
    Meirhaeghe, Aline
    Menezes, Ana Maria B.
    Merat, Shahin
    Meshram, Indrapal I.
    Mi, Jie
    Miquel, Juan Francisco
    Mohamed, Mostafa K.
    Mohammad, Kazem
    Mohan, Viswanathan
    Yusoff, Muhammad Fadhli Mohd
    Moller, Niels C.
    Molnar, Denes
    Mondo, Charles K.
    Moreno, Luis A.
    Morgan, Karen
    Moschonis, George
    Mossakowska, Malgorzata
    Mostafa, Aya
    Mota, Jorge
    Muiesan, Maria L.
    Muller-Nurasyid, Martina
    Mursu, Jaakko
    Nagel, Gabriele
    Namesna, Jana
    Nang, Ei Ei K.
    Nangia, Vinay B.
    Navarrete-Munoz, Eva Maria
    Ndiaye, Ndeye Coumba
    Nervi, Flavio
    Nguyen, Nguyen D.
    Nieto-Martinez, Ramfi S. E.
    Ning, Guang
    Ninomiya, Toshiharu
    Noale, Marianna
    Noto, Davide
    Ochoa-Aviles, Angelica M.
    Oh, Kyungwon
    Onat, Altan
    Osmond, Clive
    Otero, Johanna A.
    Palmieri, Luigi
    Panda-Jonas, Songhomitra
    Panza, Francesco
    Parsaeian, Mahboubeh
    Peixoto, Sergio Viana
    Pereira, Alexandre C.
    Peters, Annette
    Peykari, Niloofar
    Pilav, Aida
    Pitakaka, Freda
    Piwonska, Aleksandra
    Piwonski, Jerzy
    Plans-Rubio, Pedro
    Porta, Miquel
    Portegies, Marileen L. P.
    Poustchi, Hossein
    Pradeepa, Rajendra
    Price, Jacqueline F.
    Punab, Margus
    Qasrawi, Radwan F.
    Qorbani, Mostafa
    Raitakari, Olli
    Rao, Sudha Ramachandra
    Ramachandran, Ambady
    Ramos, Rafel
    Rampal, Sanjay
    Rathmann, Wolfgang
    Redon, Josep
    Reganit, Paul Ferdinand M.
    Rigo, Fernando
    Robinson, Sian M.
    Robitaille, Cynthia
    Rodriguez, Laura A.
    Rodriguez-Artalejo, Fernando
    Rodriguez-Perez, Maria del Cristo
    Rojas-Martinez, Rosalba
    Romaguera, Dora
    Rosengren, Annika
    Rubinstein, Adolfo
    Rui, Ornelas
    Ruiz-Betancourt, Blanca Sandra
    Rutkowski, Marcin
    Sabanayagam, Charumathi
    Sachdev, Harshpal S.
    Saidi, Olfa
    Sakarya, Sibel
    Salanave, Benoit
    Salonen, Jukka T.
    Salvetti, Massimo
    Sanchez-Abanto, Jose
    Nunes, Renata
    Santos, Rute
    Sardinha, Luis B.
    Scazufca, Marcia
    Schargrodsky, Herman
    Scheidt-Nave, Christa
    Shibuya, Kenji
    Shin, Youchan
    Shiri, Rahman
    Siantar, Rosalynn
    Sibai, Abla M.
    Simon, Mary
    Simons, Judith
    Simons, Leon A.
    Sjostrom, Michael
    Slowikowska-Hilczer, Jolanta
    Slusarczyk, Przemyslaw
    Smeeth, Liam
    Snijder, Marieke B.
    Solfrizzi, Vincenzo
    Sonestedt, Emily
    Soumare, Aicha
    Staessen, Jan A.
    Steene-Johannessen, Jostein
    Stehle, Peter
    Stein, Aryeh D.
    Stessman, Jochanan
    Stockl, Doris
    Stokwiszewski, Jakub
    Strufaldi, Maria Wany
    Sun, Chien-An
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Suriyawongpaisal, Paibul
    Sy, Rody G.
    Tai, E. Shyong
    Tarawneh, Mohammed
    Tarqui-Mamani, Carolina B.
    Thijs, Lutgarde
    Tolstrup, Janne S.
    Topbas, Murat
    Torrent, Maties
    Traissac, Pierre
    Trinh, Oanh T. H.
    Tulloch-Reid, Marshall K.
    Tuomainen, Tomi-Pekka
    Turley, Maria L.
    Tzourio, Christophe
    Ueda, Peter
    Ukoli, Flora M.
    Ulmer, Hanno
    Valdivia, Gonzalo
    Van Valkengoed, Irene G. M.
    Vanderschueren, Dirk
    Vanuzzo, Diego
    Vega, Tomas
    Velasquez-Melendez, Gustavo
    Veronesi, Giovanni
    Verschuren, Monique
    Vioque, Jesus
    Virtanen, Jyrki
    Visvikis-Siest, Sophie
    Viswanathan, Bharathi
    Vollenweider, Peter
    Voutilainen, Sari
    Wade, Alisha N.
    Wagner, Aline
    Walton, Janette
    Mohamud, Wan Nazaimoon Wan
    Wang, Ming-Dong
    Wang, Ya Xing
    Wannamethee, S. Goya
    Weerasekera, Deepa
    Whincup, Peter H.
    Widhalm, Kurt
    Wiecek, Andrzej
    Wilks, Rainford J.
    Willeit, Johann
    Wojtyniak, Bogdan
    Wong, Tien Yin
    Woo, Jean
    Woodward, Mark
    Wu, Aleksander Giwercman
    Wu, Frederick C.
    Wu, Shou Ling
    Xu, Haiquan
    Yang, Xiaoguang
    Ye, Xingwang
    Yoshihara, Akihiro
    Younger-Coleman, Novie O.
    Zambon, Sabina
    Zargar, Abdul Hamid
    Zdrojewski, Tomasz
    Zhao, Wenhua
    Zheng, Yingfeng
    Effects of diabetes definition on global surveillance of diabetes prevalence and diagnosis: a pooled analysis of 96 population-based studies with 331288 participants2015In: LANCET DIABETES & ENDOCRINOLOGY, ISSN 2213-8587, Vol. 3, no 8, p. 624-637Article in journal (Refereed)
    Abstract [en]

    Background Diabetes has been defined on the basis of different biomarkers, including fasting plasma glucose (FPG), 2-h plasma glucose in an oral glucose tolerance test (2hOGTT), and HbA(1c). We assessed the effect of different diagnostic definitions on both the population prevalence of diabetes and the classification of previously undiagnosed individuals as having diabetes versus not having diabetes in a pooled analysis of data from population-based health examination surveys in different regions. Methods We used data from 96 population-based health examination surveys that had measured at least two of the biomarkers used for defining diabetes. Diabetes was defined using HbA(1c) (HbA(1c) >= 6 . 5% or history of diabetes diagnosis or using insulin or oral hypoglycaemic drugs) compared with either FPG only or FPG-or-2hOGTT definitions (FPG >= 7 . 0 mmol/L or 2hOGTT >= 11 . 1 mmol/L or history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated diabetes prevalence, taking into account complex survey design and survey sample weights. We compared the prevalences of diabetes using different definitions graphically and by regression analyses. We calculated sensitivity and specificity of diabetes diagnosis based on HbA1c compared with diagnosis based on glucose among previously undiagnosed individuals (ie, excluding those with history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated sensitivity and specificity in each survey, and then pooled results using a random-effects model. We assessed the sources of heterogeneity of sensitivity by meta-regressions for study characteristics selected a priori. Findings Population prevalence of diabetes based on FPG- or-2hOGTT was correlated with prevalence based on FPG alone (r= 0 . 98), but was higher by 2-6 percentage points at different prevalence levels. Prevalence based on HbA(1c) was lower than prevalence based on FPG in 42 . 8% of age-sex-survey groups and higher in another 41 . 6%; in the other 15 . 6%, the two definitions provided similar prevalence estimates. The variation across studies in the relation between glucose-based and HbA(1c)-based prevalences was partly related to participants' age, followed by natural logarithm of per person gross domestic product, the year of survey, mean BMI, and whether the survey population was national, subnational, or from specific communities. Diabetes defined as HbA(1c) 6 . 5% or more had a pooled sensitivity of 52 . 8% (95% CI 51 . 3-54 . 3%) and a pooled specificity of 99 . 74% (99 . 71-99 . 78%) compared with FPG 7 . 0 mmol/L or more for diagnosing previously undiagnosed participants; sensitivity compared with diabetes defined based on FPG-or-2hOGTT was 30 . 5% (28 . 7-32 . 3%). None of the preselected study-level characteristics explained the heterogeneity in the sensitivity of HbA(1c) versus FPG. Interpretation Different biomarkers and definitions for diabetes can provide different estimates of population prevalence of diabetes, and differentially identify people without previous diagnosis as having diabetes. Using an HbA(1c)-based definition alone in health surveys will not identify a substantial proportion of previously undiagnosed people who would be considered as having diabetes using a glucose-based test.

    Download full text (pdf)
    fulltext
  • 91.
    de Waard, Anne-Karien M.
    et al.
    Univ Utrecht, Univ Med Ctr Utrecht, Julius Ctr, Dept Gen Practice, Utrecht, Netherlands.
    Hollander, Monika
    Univ Utrecht, Univ Med Ctr Utrecht, Julius Ctr, Dept Gen Practice, Utrecht, Netherlands.
    Korevaar, Joke C.
    Nivel Netherlands Inst Hlth Serv Res, Utrecht, Netherlands.
    Nielen, Mark M. J.
    Nivel Netherlands Inst Hlth Serv Res, Utrecht, Netherlands.
    Carlsson, Axel C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Div Family Med & Primary Care, Stockholm, Sweden.
    Lionis, Christos
    Univ Crete, Sch Med, Clin Social & Family Med, Iraklion, Greece.
    Seifert, Bohumil
    Charles Univ Prague, Fac Med 1, Inst Gen Practice, Prague, Czech Republic.
    Thilsing, Trine
    Univ Southern Denmark, Dept Publ Hlth, Res Unit Gen Practice, Odense C, Denmark.
    de Wit, Niek J.
    Univ Utrecht, Univ Med Ctr Utrecht, Julius Ctr, Dept Gen Practice, Utrecht, Netherlands.
    Schellevis, Francois G.
    Vrije Univ Amsterdam Med Ctr, Amsterdam Publ Hlth Res Inst, Dept Gen Practice & Elderly Care Med, Amsterdam, Netherlands.
    Angelaki, Agapi
    Univ Crete, Sch Med, Clin Social & Family Med, Iraklion, Greece.
    Holzmann, Martin J.
    Karolinska Inst, Dept Med, Stockholm, Sweden.
    Kral, N.
    Charles Univ Prague, Fac Med 1, Inst Gen Practice, Prague, Czech Republic.
    Sondergaard, Jens
    Sonderlund, Anders L.
    Univ Southern Denmark, Dept Publ Hlth, Res Unit Gen Practice, Odense C, Denmark.
    Wandell, P.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Div Family Med & Primary Care, Stockholm, Sweden.
    Selective prevention of cardiometabolic diseases: activities and attitudes of general practitioners across Europe2019In: European Journal of Public Health, ISSN 1101-1262, E-ISSN 1464-360X, Vol. 29, no 1, p. 88-93Article in journal (Refereed)
    Abstract [en]

    Background: Cardiometabolic diseases (CMDs) are the number one cause of death. Selective prevention of CMDs by general practitioners (GPs) could help reduce the burden of CMDs. This measure would entail the identification of individuals at high risk of CMDsubut currently asymptomaticufollowed by interventions to reduce their risk. No data were available on the attitude and the extent to which European GPs have incorporated selective CMD prevention into daily practice.

    Methods: A survey among 575 GPs from the Czech Republic, Denmark, Greece, the Netherlands and Sweden was conducted between September 2016 and January 2017, within the framework of the SPIMEU-project.

    Results: On average, 71% of GPs invited their patients to attend for CMD risk assessment. Some used an active approach (47%) while others used an opportunistic approach (53%), but these values differed between countries. Most GPs considered selective CMD prevention as useful (82%) and saw it as part of their normal duties (84%). GPs who did find selective prevention useful were more likely to actively invite individuals compared with their counterparts who did not find prevention useful. Most GPs had a disease management programme for individuals with risk factor(s) for cardiovascular disease (71%) or diabetes (86%).

    Conclusions: Although most GPs considered selective CMD prevention as useful, it was not universally implemented. The biggest challenge was the process of inviting individuals for risk assessment. It is important to tailor the implementation of selective CMD prevention in primary care to the national context, involving stakeholders at different levels.

    Download full text (pdf)
    fulltext
  • 92.
    de Waard, Anne-Karien M.
    et al.
    Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Huispost STR 6-131,POB 85500, NL-3508 GA Utrecht, Netherlands..
    Wändell, Per E.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Solna, Sweden..
    Holzmann, Martin J.
    Karolinska Univ Hosp, Funct Area Emergency Med, Solna, Sweden.;Karolinska Inst, Dept Internal Med, Stockholm, Sweden..
    Korevaar, Joke C.
    NIVEL Netherlands Inst Hlth Serv Res, Utrecht, Netherlands..
    Hollander, Monika
    Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Huispost STR 6-131,POB 85500, NL-3508 GA Utrecht, Netherlands..
    Gornitzki, Carl
    Karolinska Inst, Univ Lib, Solna, Sweden..
    de Wit, Niek J.
    Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Huispost STR 6-131,POB 85500, NL-3508 GA Utrecht, Netherlands..
    Schellevis, Francois G.
    NIVEL Netherlands Inst Hlth Serv Res, Utrecht, Netherlands.;Vrije Univ Amsterdam Med Ctr, Dept Gen Practice & Elderly Care Med, Amsterdam, Netherlands..
    Lionis, Christos
    Univ Crete, Clin Social & Family Med, Iraklion, Greece..
    Söndergaard, Jens
    Univ Southern Denmark, Res Unit Gen Practice, Odense, Denmark..
    Seifert, Bohumil
    Charles Univ Prague, Dept Gen Practice, Prague, Czech Republic..
    Carlsson, Axel C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Solna, Sweden.
    Barriers and facilitators to participation in a health check for cardiometabolic diseases in primary care: A systematic review2018In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 25, no 12, p. 1326-1340Article, review/survey (Refereed)
    Abstract [en]

    Background: Health checks for cardiometabolic diseases could play a role in the identification of persons at high risk for disease. To improve the uptake of these health checks in primary care, we need to know what barriers and facilitators determine participation.

    Methods: We used an iterative search strategy consisting of three steps: (a) identification of key-articles; (b) systematic literature search in PubMed, Medline and Embase based on keywords; (c) screening of titles and abstracts and subsequently full-text screening. We summarised the results into four categories: characteristics, attitudes, practical reasons and healthcare provider-related factors.

    Results: Thirty-nine studies were included. Attitudes such as wanting to know of cardiometabolic disease risk, feeling responsible for, and concerns about one's own health were facilitators for participation. Younger age, smoking, low education and attitudes such as not wanting to be, or being, worried about the outcome, low perceived severity or susceptibility, and negative attitude towards health checks or prevention in general were barriers. Furthermore, practical issues such as information and the ease of access to appointments could influence participation.

    Conclusion: Barriers and facilitators to participation in health checks for cardiometabolic diseases were heterogeneous. Hence, it is not possible to develop a one size fits all' approach to maximise the uptake. For optimal implementation we suggest a multifactorial approach adapted to the national context with special attention to people who might be more difficult to reach. Increasing the uptake of health checks could contribute to identifying the people at risk to be able to start preventive interventions.

    Download full text (pdf)
    fulltext
  • 93.
    Del Gobbo, Liana C.
    et al.
    Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    Imamura, Fumiaki
    Univ Cambridge, Sch Clin Med, Epidemiol Unit, Med Res Council,Inst Metab Sci, Cambridge, England..
    Aslibekyan, Stella
    Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL USA..
    Marklund, Matti
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Virtanen, Jyrki K.
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Joensuu, Finland..
    Wennberg, Maria
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Yakoob, Mohammad Y.
    Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    Chiuve, Stephanie E.
    Brigham & Womens Hosp, Dept Med, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.;Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    dela Cruz, Luicito
    Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia..
    Frazier-Wood, Alexis C.
    ARS, USDA, Childrens Nutr Res Ctr, Baylor Coll Med, Houston, TX USA..
    Fretts, Amanda M.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA..
    Guallar, Eliseo
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA..
    Matsumoto, Chisa
    Tokyo Med Univ, Div Cardiol, Tokyo, Japan.;Brigham & Womens Hosp, Div Aging, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Prem, Kiesha
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Tanaka, Tosh
    NIA, Translat Gerontol Branch, Bethesda, MD 20892 USA..
    Wu, Jason H. Y.
    Univ Sydney, George Inst Global Hlth, Sydney Med Sch, Sydney, NSW, Australia..
    Zhou, Xia
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA..
    Helmer, Catherine
    Inst Sante Publ Epidemiol & Dev, Inst Natl Sante & Rech Med, Ctr Inst Natl Sante & Rech Med Epidemiol Biostat, Bordeaux, France.;Univ Bordeaux, Inst Sante Publ Epidemiol & Dev, Ctr Inst Natl Sante & Rech Med Epidemiol Biostat, Bordeaux, France..
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    Yuan, Jian-Min
    Univ Pittsburgh, Div Canc Control & Populat Sci, Inst Canc, Pittsburgh, PA USA.;Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA..
    Barberger-Gateau, Pascale
    Inst Sante Publ Epidemiol & Dev, Inst Natl Sante & Rech Med, Ctr Inst Natl Sante & Rech Med Epidemiol Biostat, Bordeaux, France.;Univ Bordeaux, Inst Sante Publ Epidemiol & Dev, Ctr Inst Natl Sante & Rech Med Epidemiol Biostat, Bordeaux, France..
    Campos, Hannia
    Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA..
    Chaves, Paulo H. M.
    Florida Int Univ, Benjamin Leon Ctr Geriatr Res & Educ, Miami, FL 33199 USA..
    Djousse, Luc
    Brigham & Womens Hosp, Div Aging, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Giles, Graham G.
    Gomez-Aracena, Jose
    Univ Malaga, Dept Prevent Med, Malaga, Spain..
    Hodge, Allison M.
    Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia..
    Hu, Frank B.
    Harvard Med Sch, Boston, MA USA.;Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA..
    Jansson, Jan-Hakan
    Johansson, Ingegerd
    Umea Univ, Dept Odontol, Umea, Sweden..
    Khaw, Kay-Tee
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Koh, Woon-Puay
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Duke NUS Grad Med Sch Singapore, Singapore, Singapore..
    Lemaitre, Rozenn N.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Luben, Robert N.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Rimm, Eric B.
    Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.;Harvard Med Sch, Boston, MA USA.;Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA..
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Samieri, Cecilia
    Inst Sante Publ Epidemiol & Dev, Inst Natl Sante & Rech Med, Ctr Inst Natl Sante & Rech Med Epidemiol Biostat, Bordeaux, France.;Univ Bordeaux, Inst Sante Publ Epidemiol & Dev, Ctr Inst Natl Sante & Rech Med Epidemiol Biostat, Bordeaux, France..
    Franks, Paul W.
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.;Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, Lund, Sweden..
    Siscovick, David S.
    New York Acad Med, New York, NY USA..
    Stampfer, Meir
    Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.;Harvard Med Sch, Boston, MA USA.;Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA..
    Steffen, Lyn M.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA..
    Steffen, Brian T.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA..
    Tsai, Michael Y.
    Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA..
    van Dam, Rob M.
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Natl Univ Singapore, Dept Med, Yong Loo Lin Sch Med, Singapore, Singapore.;Natl Univ Hlth Syst, Singapore, Singapore..
    Voutilainen, Sari
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Joensuu, Finland..
    Willett, Walter C.
    Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.;Harvard Med Sch, Boston, MA USA.;Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA..
    Woodward, Mark
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.;Univ Sydney, George Inst Global Hlth, Sydney Med Sch, Sydney, NSW, Australia.;Univ Oxford, George Inst Global Hlth, Nuffield Dept Publ Hlth, Oxford, England..
    Mozaffarian, Dariush
    Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA..
    omega-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease Pooling Project of 19 Cohort Studies2016In: JAMA Internal Medicine, ISSN 2168-6106, E-ISSN 2168-6114, Vol. 176, no 8, p. 1155-1166Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE The role of omega-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers. OBJECTIVE To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20: 5 omega-3), docosapentaenoic acid (DPA; 22: 5 omega-3), and docosahexaenoic acid (DHA; 22: 6 omega-3) and plant-derived alpha-linolenic acid (ALA; 18: 3 omega-3) for incident CHD. DATA SOURCES A global consortium of 19 studies identified by November 2014. STUDY SELECTION Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue omega-3 biomarkers and ascertained CHD. DATA EXTRACTION AND SYNTHESIS Each study conducted standardized, individual-level analysis using harmonized models, exposures, outcomes, and covariates. Findings were centrally pooled using random-effects meta-analysis. Heterogeneity was examined by age, sex, race, diabetes, statins, aspirin, omega-6 levels, and FADS desaturase genes. MAIN OUTCOMES AND MEASURES Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI). RESULTS The 19 studies comprised 16 countries, 45 637 unique individuals, and 7973 total CHD, 2781 fatal CHD, and 7157 nonfatal MI events, with omega-3 measures in total plasma, phospholipids, cholesterol esters, and adipose tissue. Median age at baseline was 59 years (range, 18-97 years), and 28 660 (62.8%) were male. In continuous (per 1-SD increase) multivariable-adjusted analyses, the omega-3 biomarkers ALA, DPA, and DHA were associated with a lower risk of fatal CHD, with relative risks (RRs) of 0.91 (95% CI, 0.84-0.98) for ALA, 0.90 (95% CI, 0.85-0.96) for DPA, and 0.90 (95% CI, 0.84-0.96) for DHA. Although DPA was associated with a lower risk of total CHD (RR, 0.94; 95% CI, 0.90-0.99), ALA (RR, 1.00; 95% CI, 0.95-1.05), EPA (RR, 0.94; 95% CI, 0.87-1.02), and DHA (RR, 0.95; 95% CI, 0.91-1.00) were not. Significant associations with nonfatal MI were not evident. Associations appeared generally stronger in phospholipids and total plasma. Restricted cubic splines did not identify evidence of nonlinearity in dose responses. CONCLUSIONS AND RELEVANCE On the basis of available studies of free-living populations globally, biomarker concentrations of seafood and plant-derived omega-3 fatty acids are associated with a modestly lower incidence of fatal CHD.

  • 94. Deloukas, Panos
    et al.
    Kanoni, Stavroula
    Willenborg, Christina
    Farrall, Martin
    Assimes, Themistocles L
    Thompson, John R
    Ingelsson, Erik
    Saleheen, Danish
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Erdmann, Jeanette
    Goldstein, Benjamin A
    Stirrups, Kathleen
    König, Inke R
    Cazier, Jean-Baptiste
    Johansson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hall, Alistair S
    Lee, Jong-Young
    Willer, Cristen J
    Chambers, John C
    Esko, Tõnu
    Folkersen, Lasse
    Goel, Anuj
    Grundberg, Elin
    Havulinna, Aki S
    Ho, Weang K
    Hopewell, Jemma C
    Eriksson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Kleber, Marcus E
    Kristiansson, Kati
    Lundmark, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Lyytikäinen, Leo-Pekka
    Rafelt, Suzanne
    Shungin, Dmitry
    Strawbridge, Rona J
    Thorleifsson, Gudmar
    Tikkanen, Emmi
    van Zuydam, Natalie
    Voight, Benjamin F
    Waite, Lindsay L
    Zhang, Weihua
    Ziegler, Andreas
    Absher, Devin
    Altshuler, David
    Balmforth, Anthony J
    Barroso, Inês
    Braund, Peter S
    Burgdorf, Christof
    Claudi-Boehm, Simone
    Cox, David
    Dimitriou, Maria
    Do, Ron
    Doney, Alex S F
    Mokhtari, Noureddine El
    Eriksson, Per
    Fischer, Krista
    Fontanillas, Pierre
    Franco-Cereceda, Anders
    Gigante, Bruna
    Groop, Leif
    Gustafsson, Stefan
    Hager, Jörg
    Hallmans, Göran
    Han, Bok-Ghee
    Hunt, Sarah E
    Kang, Hyun M
    Illig, Thomas
    Kessler, Thorsten
    Knowles, Joshua W
    Kolovou, Genovefa
    Kuusisto, Johanna
    Langenberg, Claudia
    Langford, Cordelia
    Leander, Karin
    Lokki, Marja-Liisa
    Lundmark, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    McCarthy, Mark I
    Meisinger, Christa
    Melander, Olle
    Mihailov, Evelin
    Maouche, Seraya
    Morris, Andrew D
    Müller-Nurasyid, Martina
    Nikus, Kjell
    Peden, John F
    Rayner, N William
    Rasheed, Asif
    Rosinger, Silke
    Rubin, Diana
    Rumpf, Moritz P
    Schäfer, Arne
    Sivananthan, Mohan
    Song, Ci
    Stewart, Alexandre F R
    Tan, Sian-Tsung
    Thorgeirsson, Gudmundur
    Schoot, C Ellen van der
    Wagner, Peter J
    Wells, George A
    Wild, Philipp S
    Yang, Tsun-Po
    Amouyel, Philippe
    Arveiler, Dominique
    Basart, Hanneke
    Boehnke, Michael
    Boerwinkle, Eric
    Brambilla, Paolo
    Cambien, Francois
    Cupples, Adrienne L
    de Faire, Ulf
    Dehghan, Abbas
    Diemert, Patrick
    Epstein, Stephen E
    Evans, Alun
    Ferrario, Marco M
    Ferrières, Jean
    Gauguier, Dominique
    Go, Alan S
    Goodall, Alison H
    Gudnason, Villi
    Hazen, Stanley L
    Holm, Hilma
    Iribarren, Carlos
    Jang, Yangsoo
    Kähönen, Mika
    Kee, Frank
    Kim, Hyo-Soo
    Klopp, Norman
    Koenig, Wolfgang
    Kratzer, Wolfgang
    Kuulasmaa, Kari
    Laakso, Markku
    Laaksonen, Reijo
    Lee, Ji-Young
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ouwehand, Willem H
    Parish, Sarah
    Park, Jeong E
    Pedersen, Nancy L
    Peters, Annette
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Quertermous, Thomas
    Rader, Daniel J
    Salomaa, Veikko
    Schadt, Eric
    Shah, Svati H
    Sinisalo, Juha
    Stark, Klaus
    Stefansson, Kari
    Trégouët, David-Alexandre
    Virtamo, Jarmo
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wareham, Nicholas
    Zimmermann, Martina E
    Nieminen, Markku S
    Hengstenberg, Christian
    Sandhu, Manjinder S
    Pastinen, Tomi
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Hovingh, G Kees
    Dedoussis, George
    Franks, Paul W
    Lehtimäki, Terho
    Metspalu, Andres
    Zalloua, Pierre A
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Schreiber, Stefan
    Ripatti, Samuli
    Blankenberg, Stefan S
    Perola, Markus
    Clarke, Robert
    Boehm, Bernhard O
    O'Donnell, Christopher
    Reilly, Muredach P
    März, Winfried
    Collins, Rory
    Kathiresan, Sekar
    Hamsten, Anders
    Kooner, Jaspal S
    Thorsteinsdottir, Unnur
    Danesh, John
    Palmer, Colin N A
    Roberts, Robert
    Watkins, Hugh
    Schunkert, Heribert
    Samani, Nilesh J
    Large-scale association analysis identifies new risk loci for coronary artery disease2013In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, no 1, p. 25-33Article in journal (Refereed)
    Abstract [en]

    Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r2 < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.

  • 95.
    den Hoed, Marcel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Eijgelsheim, Mark
    Esko, Tonu
    Brundel, Bianca J. J. M.
    Peal, David S.
    Evans, David M.
    Nolte, Ilja M.
    Segre, Ayellet V.
    Holm, Hilma
    Handsaker, Robert E.
    Westra, Harm-Jan
    Johnson, Toby
    Isaacs, Aaron
    Yang, Jian
    Lundby, Alicia
    Zhao, Jing Hua
    Kim, Young Jin
    Go, Min Jin
    Almgren, Peter
    Bochud, Murielle
    Boucher, Gabrielle
    Cornelis, Marilyn C.
    Gudbjartsson, Daniel
    Hadley, David
    van der Harst, Pim
    Hayward, Caroline
    den Heijer, Martin
    Igl, Wilmar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Jackson, Anne U.
    Kutalik, Zoltan
    Luan, Jian'an
    Kemp, John P.
    Kristiansson, Kati
    Ladenvall, Claes
    Lorentzon, Mattias
    Montasser, May E.
    Njajou, Omer T.
    O'Reilly, Paul F.
    Padmanabhan, Sandosh
    Pourcain, Beate St.
    Rankinen, Tuomo
    Salo, Perttu
    Tanaka, Toshiko
    Timpson, Nicholas J.
    Vitart, Veronique
    Waite, Lindsay
    Wheeler, William
    Zhang, Weihua
    Draisma, Harmen H. M.
    Feitosa, Mary F.
    Kerr, Kathleen F.
    Lind, Penelope A.
    Mihailov, Evelin
    Onland-Moret, N. Charlotte
    Song, Ci
    Weedon, Michael N.
    Xie, Weijia
    Yengo, Loic
    Absher, Devin
    Albert, Christine M.
    Alonso, Alvaro
    Arking, Dan E.
    de Bakker, Paul I. W.
    Balkau, Beverley
    Barlassina, Cristina
    Benaglio, Paola
    Bis, Joshua C.
    Bouatia-Naji, Nabila
    Brage, Soren
    Chanock, Stephen J.
    Chines, Peter S.
    Chung, Mina
    Darbar, Dawood
    Dina, Christian
    Doerr, Marcus
    Elliott, Paul
    Felix, Stephan B.
    Fischer, Krista
    Fuchsberger, Christian
    de Geus, Eco J. C.
    Goyette, Philippe
    Gudnason, Vilmundur
    Harris, Tamara B.
    Hartikainen, Anna-Liisa
    Havulinna, Aki S.
    Heckbert, Susan R.
    Hicks, Andrew A.
    Hofman, Albert
    Holewijn, Suzanne
    Hoogstra-Berends, Femke
    Hottenga, Jouke-Jan
    Jensen, Majken K.
    Johansson, Asa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Junttila, Juhani
    Kaeaeb, Stefan
    Kanon, Bart
    Ketkar, Shamika
    Khaw, Kay-Tee
    Knowles, Joshua W.
    Kooner, Angrad S.
    Kors, Jan A.
    Kumari, Meena
    Milani, Lili
    Laiho, Paeivi
    Lakatta, Edward G.
    Langenberg, Claudia
    Leusink, Maarten
    Liu, Yongmei
    Luben, Robert N.
    Lunetta, Kathryn L.
    Lynch, Stacey N.
    Markus, Marcello R. P.
    Marques-Vidal, Pedro
    Leach, Irene Mateo
    McArdle, Wendy L.
    McCarroll, Steven A.
    Medland, Sarah E.
    Miller, Kathryn A.
    Montgomery, Grant W.
    Morrison, Alanna C.
    Mueller-Nurasyid, Martina
    Navarro, Pau
    Nelis, Mari
    O'Connell, Jeffrey R.
    O'Donnell, Christopher J.
    Ong, Ken K.
    Newman, Anne B.
    Peters, Annette
    Polasek, Ozren
    Pouta, Anneli
    Pramstaller, Peter P.
    Psaty, Bruce M.
    Rao, Dabeeru C.
    Ring, Susan M.
    Rossin, Elizabeth J.
    Rudan, Diana
    Sanna, Serena
    Scott, Robert A.
    Sehmi, Jaban S.
    Sharp, Stephen
    Shin, Jordan T.
    Singleton, Andrew B.
    Smith, Albert V.
    Soranzo, Nicole
    Spector, Tim D.
    Stewart, Chip
    Stringham, Heather M.
    Tarasov, Kirill V.
    Uitterlinden, Andre G.
    Vandenput, Liesbeth
    Hwang, Shih-Jen
    Whitfield, John B.
    Wijmenga, Cisca
    Wild, Sarah H.
    Willemsen, Gonneke
    Wilson, James F.
    Witteman, Jacqueline C. M.
    Wong, Andrew
    Wong, Quenna
    Jamshidi, Yalda
    Zitting, Paavo
    Boer, Jolanda M. A.
    Boomsma, Dorret I.
    Borecki, Ingrid B.
    van Duijn, Cornelia M.
    Ekelund, Ulf
    Forouhi, Nita G.
    Froguel, Philippe
    Hingorani, Aroon
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kivimaki, Mika
    Kronmal, Richard A.
    Kuh, Diana
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Martin, Nicholas G.
    Oostra, Ben A.
    Pedersen, Nancy L.
    Quertermous, Thomas
    Rotter, Jerome I.
    van der Schouw, Yvonne T.
    Verschuren, W. M. Monique
    Walker, Mark
    Albanes, Demetrius
    Arnar, David O.
    Assimes, Themistocles L.
    Bandinelli, Stefania
    Boehnke, Michael
    de Boer, Rudolf A.
    Bouchard, Claude
    Caulfield, W. L. Mark
    Chambers, John C.
    Curhan, Gary
    Cusi, Daniele
    Eriksson, Johan
    Ferrucci, Luigi
    van Gilst, Wiek H.
    Glorioso, Nicola
    de Graaf, Jacqueline
    Groop, Leif
    Gyllensten, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Hsueh, Wen-Chi
    Hu, Frank B.
    Huikuri, Heikki V.
    Hunter, David J.
    Iribarren, Carlos
    Isomaa, Bo
    Jarvelin, Marjo-Riitta
    Jula, Antti
    Kahonen, Mika
    Kiemeney, Lambertus A.
    van der Klauw, Melanie M.
    Kooner, Jaspal S.
    Kraft, Peter
    Iacoviello, Licia
    Lehtimaki, Terho
    Lokki, Marja-Liisa L.
    Mitchell, Braxton D.
    Navis, Gerjan
    Nieminen, Markku S.
    Ohlsson, Claes
    Poulter, Neil R.
    Qi, Lu
    Raitakari, Olli T.
    Rimm, Eric B.
    Rioux, John D.
    Rizzi, Federica
    Rudan, Igor
    Salomaa, Veikko
    Sever, Peter S.
    Shields, Denis C.
    Shuldiner, Alan R.
    Sinisalo, Juha
    Stanton, Alice V.
    Stolk, Ronald P.
    Strachan, David P.
    Tardif, Jean-Claude
    Thorsteinsdottir, Unnur
    Tuomilehto, Jaako
    van Veldhuisen, Dirk J.
    Virtamo, Jarmo
    Viikari, Jorma
    Vollenweider, Peter
    Waeber, Gerard
    Widen, Elisabeth
    Cho, Yoon Shin
    Olsen, Jesper V.
    Visscher, Peter M.
    Willer, Cristen
    Franke, Lude
    Erdmann, Jeanette
    Thompson, John R.
    Pfeufer, Arne
    Sotoodehnia, Nona
    Newton-Cheh, Christopher
    Ellinor, Patrick T.
    Stricker, Bruno H. Ch
    Metspalu, Andres
    Perola, Markus
    Beckmann, Jacques S.
    Smith, George Davey
    Stefansson, Kari
    Wareham, Nicholas J.
    Munroe, Patricia B.
    Sibon, Ody C. M.
    Milan, David J.
    Snieder, Harold
    Samani, Nilesh J.
    Loos, Ruth J. F.
    Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders2013In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, no 6, p. 621-+Article in journal (Refereed)
    Abstract [en]

    Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.

  • 96.
    den Hoed, Marcel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Strawbridge, Rona J
    Almgren, Peter
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Axelsson, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Engström, Gunnar
    de Faire, Ulf
    Hedblad, Bo
    Humphries, Steve E
    Lindgren, Cecilia M
    Morris, Andrew P
    Östling, Gerd
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Tremoli, Elena
    Hamsten, Anders
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Melander, Olle
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    GWAS-identified loci for coronary heart disease are associated with intima-media thickness and plaque presence at the carotid artery bulb2015In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 239, no 2, p. 304-310Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Large-scale genome-wide association studies (GWAS) have so far identified 45 loci that are robustly associated with coronary heart disease (CHD) in data from adult men and women of European descent.

    OBJECTIVES: To examine whether the CHD-associated loci are associated with measures of atherosclerosis in data from up to 9582 individuals of European ancestry.

    METHODS: Forty-five SNPs representing the CHD-associated loci were genotyped in middle-aged to elderly individuals of European descent from four independent population-based studies (IMPROVE, MDC-CC, ULSAM and PIVUS). Intima-media thickness (IMT) was measured by external B-mode ultrasonography at the far wall of the bulb (sinus) and common carotid artery. Plaque presence was defined as a maximal IMT of the bulb >1.5 mm. We meta-analysed single-SNP associations across the four studies, and combined them in a genetic predisposition score. We subsequently examined the association of the genetic predisposition score with prevalent CHD and the three indices of atherosclerosis, adjusting for sex, age and Framingham risk factors.

    RESULTS: As anticipated, the genetic predisposition score was associated with prevalent CHD, with each additional risk allele increasing the odds of disease by 5.5% (p = 4.1 × 10(-6)). Moreover, each additional CHD-risk allele across the 45 loci was associated with a 0.24% increase in IMT (p = 4.0 × 10(-3)), and with a 2.8% increased odds of plaque presence (p = 7.4 × 10(-6)) at the far wall of the bulb. The genetic predisposition score was not associated with IMT of the common carotid artery (p = 0.47).

    CONCLUSIONS: Our results suggest that the association between the 45 previously identified loci and CHD at least partly acts through atherosclerosis.

  • 97.
    Di Cesare, Mariachiara
    et al.
    Univ London Imperial Coll Sci Technol & Med, London, England.;Middlesex Univ, London N17 8HR, England..
    Bentham, James
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Stevens, Gretchen A.
    WHO, CH-1211 Geneva, Switzerland..
    Zhou, Bin
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Danaei, Goodarz
    Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA..
    Lu, Yuan
    Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA..
    Bixby, Honor
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Cowan, Melanie J.
    WHO, CH-1211 Geneva, Switzerland..
    Riley, Leanne M.
    WHO, CH-1211 Geneva, Switzerland..
    Hajifathalian, Kaveh
    Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA..
    Fortunato, Lea
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Taddei, Cristina
    Univ Florence, Florence, Italy..
    Bennett, James E.
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Ikeda, Nayu
    Natl Inst Hlth & Nutr, Tokyo 162, Japan..
    Khang, Young-Ho
    Seoul Natl Univ, Seoul, South Korea..
    Kyobutungi, Catherine
    African Populat & Hlth Res Ctr, Nairobi, Kenya..
    Laxmaiah, Avula
    Indian Council Med Res, New Delhi, India..
    Li, Yanping
    Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA..
    Lin, Hsien-Ho
    Natl Taiwan Univ, Taipei 10764, Taiwan..
    Miranda, J. Jaime
    Univ Peruana Cayetano Heredia, Lima, Peru..
    Mostafa, Aya
    Ain Shams Univ, Cairo, Egypt..
    Turley, Maria L.
    Minist Hlth, Wellington, New Zealand..
    Paciorek, Christopher J.
    Univ Calif Berkeley, Berkeley, CA 94720 USA..
    Gunter, Marc
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Ezzati, Majid
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Abdeen, Ziad A.
    Al Quds Univ, Jerusalem, Israel..
    Hamid, Zargar Abdul
    Ctr Diabet & Endocrine Care, Bengaluru, India..
    Abu-Rmeileh, Niveen M.
    Birzeit Univ, Bir Zayt, Israel..
    Acosta-Cazares, Benjamin
    Inst Mexicano Seguro Social, Rio Grande, Mexico..
    Adams, Robert
    Univ Adelaide, Adelaide, SA 5005, Australia..
    Aekplakorn, Wichai
    Mahidol Univ, Bangkok 10700, Thailand..
    Aguilar-Salinas, Carlos A.
    Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Rio Grande, Mexico..
    Ahmadvand, Alireza
    Noncommunicable Dis Res Ctr, Tehran, Iran..
    Ahrens, Wolfgang
    Leibniz Inst Prevent Res & Epidemiol BIPS, Leibniz, Germany..
    Ali, Mohamed M.
    World Hlth Org Reg Off Eastern Mediterranean, Giza, Egypt..
    Alkerwi, Ala'a
    Luxembourg Inst Hlth, Luxembourg, Luxembourg..
    Alvarez-Pedrerol, Mar
    Ctr Res Environm Epidemiol, Madrid, Spain..
    Aly, Eman
    World Hlth Org Reg Off Eastern Mediterranean, Giza, Egypt..
    Amouyel, Philippe
    Lille Univ & Hosp, Lille, France..
    Amuzu, Antoinette
    London Sch Hyg & Trop Med, London, England..
    Andersen, Lars Bo
    Univ Southern Denmark, Lyngby, Denmark..
    Anderssen, Sigmund A.
    Norwegian Sch Sport Sci, Oslo, Norway..
    Andrade, Dolores S.
    Univ Cuenca, Cuenca, Ecuador..
    Anjana, Ranjit Mohan
    Madras Diabet Res Fdn, Madras, Tamil Nadu, India..
    Aounallah-Skhiri, Hajer
    Natl Inst Publ Hlth, Tunis, Tunisia..
    Ariansen, Inger
    Norwegian Inst Publ Hlth, Oslo, Norway..
    Aris, Tahir
    Minist Hlth, Kuala Lumpur, Malaysia..
    Arlappa, Nimmathota
    Indian Council Med Res, New Delhi, India..
    Arveiler, Dominique
    Strasbourg Univ & Hosp, Strasbourg, France..
    Assah, Felix K.
    Univ Yaounde I, Yaounde, Cameroon..
    Avdicova, Maria
    Reg Author Publ Hlth, Banska Bystrica, Slovakia..
    Azizi, Fereidoun
    Shahid Beheshti Univ Med Sci, Tehran, Iran..
    Babu, Bontha V.
    Indian Council Med Res, New Delhi, India..
    Balakrishna, Nagalla
    Indian Council Med Res, New Delhi, India..
    Bandosz, Piotr
    Med Univ Gdansk, Gdansk, Poland..
    Banegas, Jose R.
    Univ Autonoma Madrid, E-28049 Madrid, Spain..
    Barbagallo, Carlo M.
    Univ Palermo, I-90133 Palermo, Italy..
    Barcelo, Alberto
    Pan Amer Hlth Org, El Paso, TX USA..
    Barkat, Amina
    Univ Mohammed V Rabat, Rabat, Morocco..
    Barros, Mauro V.
    Univ Pernambuco, Petrolina, PE, Brazil..
    Bata, Iqbal
    Dalhousie Univ, Halifax, NS B3H 3J5, Canada..
    Batieha, Anwar M.
    Jordan Univ Sci & Technol, Amman, Jordan..
    Batista, Rosangela L.
    Univ Fed Maranhao, Sao Luis, Brazil..
    Baur, Louise A.
    Univ Sydney, Sydney, NSW 2006, Australia..
    Beaglehole, Robert
    Univ Auckland, Auckland 1, New Zealand..
    Ben Romdhane, Habiba
    Univ Tunis El Manar, Tunis, Tunisia..
    Benet, Mikhail
    Univ Med Sci, Havana, Cuba..
    Bernabe-Ortiz, Antonio
    Univ Peruana Cayetano Heredia, Lima, Peru..
    Bernotiene, Gailute
    Lithuanian Univ Hlth Sci, Kaunas, Lithuania..
    Bettiol, Heloisa
    Univ Sao Paulo, BR-05508 Sao Paulo, Brazil..
    Bhagyalaxmi, Aroor
    BJ Med Coll, New Delhi, India..
    Bharadwaj, Sumit
    Chirayu Med Coll, Bhopal, India..
    Bhargava, Santosh K.
    Sunder Lal Jain Hosp, New Delhi, India..
    Bhatti, Zaid
    Aga Khan Univ, Lahore, Pakistan..
    Bhutta, Zulfiqar A.
    Aga Khan Univ, Lahore, Pakistan..
    Bi, HongSheng
    Shandong Univ Tradit Chinese Med, Jinan, Peoples R China..
    Bi, Yufang
    Shanghai Jiao Tong Univ, Sch Med, Shanghai 200030, Peoples R China..
    Bjerregaard, Peter
    Univ Southern Denmark, Lyngby, Denmark..
    Bjertness, Espen
    Univ Oslo, N-0316 Oslo, Norway..
    Bjertness, Marius B.
    Univ Oslo, N-0316 Oslo, Norway..
    Bjorkelund, Cecilia
    Gothenburg Univ, S-41124 Gothenburg, Sweden..
    Blake, Margaret
    NatCen Social Res, London, England..
    Blokstra, Anneke
    Natl Inst Publ Hlth & Environm, Amsterdam, Netherlands..
    Bo, Simona
    Univ Turin, I-10124 Turin, Italy..
    Bobak, Martin
    UCL, London WC1E 6BT, England..
    Boddy, Lynne M.
    Liverpool John Moores Univ, Liverpool L3 5UX, Merseyside, England..
    Boehm, Bernhard O.
    Nanyang Technol Univ, Singapore 639798, Singapore..
    Boeing, Heiner
    German Inst Human Nutr, Berlin, Germany..
    Boissonnet, Carlos P.
    CEMIC, Buenos Aires, DF, Argentina..
    Bongard, Vanina
    Toulouse Univ, Sch Med, Toulouse, France..
    Bovet, Pascal
    Minist Hlth, Victoria, Seychelles.;Univ Lausanne, CH-1015 Lausanne, Switzerland..
    Braeckman, Lutgart
    Univ Ghent, B-9000 Ghent, Belgium..
    Bragt, Marjolijn C. E.
    FrieslandCampina, Singapore, Singapore..
    Brajkovich, Imperia
    Cent Univ Venezuela, Caracas, Venezuela..
    Branca, Francesco
    WHO, CH-1211 Geneva, Switzerland..
    Breckenkamp, Juergen
    Univ Bielefeld, Bielefeld, Germany..
    Brenner, Hermann
    German Canc Res Ctr, Berlin, Germany..
    Brewster, Lizzy M.
    Univ Amsterdam, NL-1012 WX Amsterdam, Netherlands..
    Brian, Garry R.
    Fred Hollows Fdn New Zealand, Auckland, New Zealand..
    Bruno, Graziella
    Univ Turin, I-10124 Turin, Italy..
    Bueno-de-Mesquita, H. B(as)
    Natl Inst Publ Hlth & Environm, Amsterdam, Netherlands..
    Bugge, Anna
    Univ Southern Denmark, Lyngby, Denmark..
    Burns, Con
    Cork Inst Technol, Cork, Ireland..
    Cabrera de Leon, Antonio
    Univ La Laguna, E-38207 San Cristobal la Laguna, Spain..
    Cacciottolo, Joseph
    Univ Malta, Msida, Malta..
    Cama, Tilema
    Minist Hlth, Nukualofa, Tonga..
    Cameron, Christine
    Canadian Fitness & Lifestyle Res Inst, Toronto, ON, Canada..
    Camolas, Jose
    Hosp Santa Maria, CHLN, Lisbon, Portugal..
    Can, Gunay
    Istanbul Univ, Istanbul, Turkey..
    Candido, Ana Paula C.
    Univ Fed Juiz de Fora, Juiz De Fora, Brazil..
    Capuano, Vincenzo
    Cardiol Mercato S Severino, Mercato San Severino, Italy..
    Cardoso, Viviane C.
    Univ Sao Paulo, BR-05508 Sao Paulo, Brazil..
    Carvalho, Maria J.
    Univ Porto, Rua Campo Alegre 823, P-4100 Oporto, Portugal..
    Casanueva, Felipe F.
    Univ Santiago de Compostela, Santiago De Compostela, Spain..
    Casas, Juan-Pablo
    UCL, London WC1E 6BT, England..
    Caserta, Carmelo A.
    Assoc Calabrese Epatol, Rome, Italy..
    Castetbon, Katia
    French Inst Hlth Surveillance, Lyon, France..
    Chamukuttan, Snehalatha
    India Diabet Res Fdn, New Delhi, India..
    Chan, Angelique W.
    Duke NUS Grad Med Sch, Singapore, Singapore..
    Chan, Queenie
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Chaturvedi, Himanshu K.
    Natl Inst Med Stat, New Delhi, India..
    Chaturvedi, Nishi
    UCL, London WC1E 6BT, England..
    Chen, Chien-Jen
    Acad Sinica, Taipei, Taiwan..
    Chen, Fangfang
    Capital Inst Pediat, Beijing, Peoples R China..
    Chen, Huashuai
    Duke Univ, Durham, NC 27706 USA..
    Chen, Shuohua
    Kailuan Gen Hosp, Beijing, Peoples R China..
    Chen, Zhengming
    Univ Oxford, Oxford OX1 2JD, England..
    Cheng, Ching-Yu
    Duke NUS Grad Med Sch, Singapore, Singapore..
    Chetrit, Angela
    Gertner Inst Epidemiol & Hlth Policy Res, Tel Aviv, Israel..
    Chiolero, Arnaud
    Univ Lausanne Hosp, Lausanne, Switzerland..
    Chiou, Shu-Ti
    Minist Hlth & Welf, Taipei, Taiwan..
    Chirita-Emandi, Adela
    Victor Babes Univ Med & Pharm, Cluj Napoca, Romania..
    Cho, Yumi
    Korea Ctr Dis Control & Prevent, Seoul, South Korea..
    Christensen, Kaare
    Univ Southern Denmark, Lyngby, Denmark..
    Chudek, Jerzy
    Med Univ Silesia, Katowice, Poland..
    Cifkova, Renata
    Charles Univ Prague, Prague, Czech Republic..
    Claessens, Frank
    Katholieke Univ Leuven, Louvain, Belgium..
    Clays, Els
    Univ Ghent, B-9000 Ghent, Belgium..
    Concin, Hans
    Agcy Prevent & Social Med, Vienna, Austria..
    Cooper, Cyrus
    Univ Southampton, Southampton SO9 5NH, Hants, England..
    Cooper, Rachel
    UCL, London WC1E 6BT, England..
    Coppinger, Tara C.
    Cork Inst Technol, Cork, Ireland..
    Costanzo, Simona
    IRCCS Ist Neurol Mediterraneo Neuromed, Rome, Italy..
    Cottel, Dominique
    Inst Pasteur, Lille, France..
    Cowell, Chris
    Westmead Univ Sydney, Sydney, NSW, Australia..
    Craig, Cora L.
    Canadian Fitness & Lifestyle Res Inst, Toronto, ON, Canada..
    Crujeiras, Ana B.
    CIBEROBN, Madrid, Spain..
    D'Arrigo, Graziella
    CNR, Rome, Italy..
    d'Orsi, Eleonora
    Univ Fed Santa Catarina, BR-88040900 Florianopolis, SC, Brazil..
    Dallongeville, Jean
    Inst Pasteur, Lille, France..
    Damasceno, Albertino
    Eduardo Mondlane Univ, Maputo, Mozambique..
    Damsgaard, Camilla T.
    Univ Copenhagen, DK-1168 Copenhagen, Denmark..
    Dankner, Rachel
    Gertner Inst Epidemiol & Hlth Policy Res, Tel Aviv, Israel..
    Dauchet, Luc
    Lille Univ Hosp, Lille, France..
    De Backer, Guy
    Univ Ghent, B-9000 Ghent, Belgium..
    De Bacquer, Dirk
    Univ Ghent, B-9000 Ghent, Belgium..
    de Gaetano, Giovanni
    IRCCS Ist Neurol Mediterraneo Neuromed, Rome, Italy..
    De Henauw, Stefaan
    Univ Ghent, B-9000 Ghent, Belgium..
    De Smedt, Delphine
    Univ Ghent, B-9000 Ghent, Belgium..
    Deepa, Mohan
    Madras Diabet Res Fdn, Madras, Tamil Nadu, India..
    Deev, Alexander D.
    Natl Res Ctr Prevent Med, Moscow, Russia..
    Dehghan, Abbas
    Erasmus MC, Rotterdam, Netherlands.;Univ Amsterdam, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands..
    Delisle, Helene
    Univ Montreal, Montreal, PQ H3C 3J7, Canada..
    Delpeuch, Francis
    Inst Rech Dev, Lyon, France..
    Dhana, Klodian
    Erasmus MC, Rotterdam, Netherlands..
    Di Castelnuovo, Augusto F.
    IRCCS Ist Neurol Mediterraneo Neuromed, Rome, Italy..
    Dias-da-Costa, Juvenal Soares
    Univ Vale Rio dos Sinos, Sao Leopoldo, RS, Brazil..
    Diaz, Alejandro
    Natl Council Sci & Tech Res, Buenos Aires, DF, Argentina..
    Djalalinia, Shirin
    Noncommunicable Dis Res Ctr, Tehran, Iran..
    Do, Ha T. P.
    Natl Inst Nutr, Hanoi, Vietnam..
    Dobson, Annette J.
    Univ Queensland, Brisbane, Qld 4072, Australia..
    Donfrancesco, Chiara
    Ist Super Sanita, Rome, Italy..
    Doering, Angela
    Helmholtz Zentrum mUNCHEN, Munich, Germany..
    Doua, Kouamelan
    Minist Sante & Lutte Sida, Yamoussoukro, Cote Ivoire..
    Drygas, Wojciech
    Cardinal Wyszynski Inst Cardiol, Warsaw, Poland..
    Egbagbe, Eruke E.
    Univ Benin, Coll Med Sci, Benin, Nigeria..
    Eggertsen, Robert
    Gothenburg Univ, S-41124 Gothenburg, Sweden..
    Ekelund, Ulf
    Norwegian Sch Sport Sci, Oslo, Norway..
    El Ati, Jalila
    Natl Inst Nutr & Food Technol, Tunis, Tunisia..
    Elliott, Paul
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Engle-Stone, Reina
    Univ Calif Davis, Davis, CA USA..
    Erasmus, Rajiv T.
    Univ Stellenbosch, ZA-7600 Stellenbosch, South Africa..
    Erem, Cihangir
    Karadeniz Tech Univ, Trabzon, Turkey..
    Eriksen, Louise
    Univ Southern Denmark, Lyngby, Denmark..
    Escobedo-de la Pena, Jorge
    Inst Mexicano Seguro Social, Rio Grande, Mexico..
    Evans, Alun
    Queens Univ Belfast, Belfast BT7 1NN, Antrim, North Ireland..
    Faeh, David
    Univ Zurich, CH-8006 Zurich, Switzerland..
    Fall, Caroline H.
    Univ Southampton, Southampton SO9 5NH, Hants, England.;Univ Tehran Med Sci, Tehran, Iran..
    Farzadfar, Farshad
    Felix-Redondo, Francisco J.
    Ferguson, Trevor S.
    Univ W Indies, Kingston, Jamaica..
    Fernandez-Berges, Daniel
    Ferrante, Daniel
    Minist Hlth, Buenos Aires, DF, Argentina..
    Ferrari, Marika
    Council Agr Res & Econ, Rome, Italy..
    Ferreccio, Catterina
    Ferrieres, Jean
    Toulouse Univ, Sch Med, Toulouse, France..
    Finn, Joseph D.
    Univ Manchester, Manchester M13 9PL, Lancs, England..
    Fischer, Krista
    Univ Tartu, Tartu, Estonia..
    Monterubio Flores, Eric
    Inst Nacl Salud Publ, Mexico City, DF, Mexico..
    Foeger, Bernhard
    Agcy Prevent & Social Med, Vienna, Austria..
    Foo, Leng Huat
    Univ Sains Malaysia, Shah Alam, Malaysia..
    Forslund, Ann-Sofie
    Univ Lulea, S-97187 Lulea, Sweden..
    Fortmann, Stephen P.
    Stanford Univ, Stanford, CA 94305 USA..
    Fouad, Heba M.
    Francis, Damian K.
    Franco, Maria do Carmo
    Franco, Oscar H.
    Erasmus MC, Rotterdam, Netherlands.;Univ Fed Sao Paulo, Sao Paulo, Brazil..
    Frontera, Guillermo
    Fuchs, Flavio D.
    Fuchs, Sandra C.
    Univ Fed Rio Grande do Sul, BR-90046900 Porto Alegre, RS, Brazil..
    Fujita, Yuki
    Kinki Univ, Fac Med, Higashiosaka, Osaka 577, Japan..
    Furusawa, Takuro
    Kyoto Univ, Kyoto 6068501, Japan..
    Gaciong, Zbigniew
    Med Univ Warsaw, Warsaw, Poland..
    Gafencu, Mihai
    Victor Babes Univ Med & Pharm, Cluj Napoca, Romania..
    Gareta, Dickman
    Garnett, Sarah P.
    Univ Sydney, Sydney, NSW 2006, Australia..
    Gaspoz, Jean-Michel
    Univ Hosp Geneva, Geneva, Switzerland..
    Gasull, Magda
    Gates, Louise
    Geleijnse, Johanna M.
    Wageningen Univ, NL-6700 AP Wageningen, Netherlands..
    Ghasemian, Anoosheh
    Noncommunicable Dis Res Ctr, Tehran, Iran..
    Giampaoli, Simona
    Ist Super Sanita, Rome, Italy..
    Gianfagna, Francesco
    Univ Insubria, Varese, Italy..
    Giovannelli, Jonathan
    Lille Univ Hosp, Lille, France..
    Giwercman, Aleksander
    Lund Univ, S-22100 Lund, Sweden..
    Goldsmith, Rebecca A.
    Gonzalez Gross, Marcela
    Univ Politecn Madrid, E-28040 Madrid, Spain..
    Gonzalez Rivas, Juan P.
    Andes Clin Cardiometab Studies, Caracas, Venezuela..
    Bonet Gorbea, Mariano
    Natl Inst Hyg Epidemiol & Microbiol, Havana, Cuba..
    Gottrand, Frederic
    Univ Lille 2, F-59800 Lille, France..
    -Iversen, Sidsel Graff
    Norwegian Inst Publ Hlth, Oslo, Norway..
    Grafnetter, Dusan
    Inst Clin & Expt Med, Prague, Czech Republic..
    Grajda, Aneta
    Childrens Mem Hlth Inst, Warsaw, Poland..
    Grammatikopoulou, Maria G.
    Alexander Technol Educ Inst, Athens, Greece..
    Gregor, Ronald D.
    Dalhousie Univ, Halifax, NS B3H 3J5, Canada..
    Grodzicki, Tomasz
    Jagiellonian Univ, Coll Med, PL-31007 Krakow, Poland..
    Grontved, Anders
    Univ Southern Denmark, Lyngby, Denmark..
    Gruden, Grabriella
    Univ Turin, I-10124 Turin, Italy..
    Grujic, Vera
    Inst Publ Hlth Vojvodina, Belgrade, Serbia..
    Gu, Dongfeng
    Natl Ctr Cardiovasc Dis, Beijing, Peoples R China..
    Guan, Ong Peng
    Singapore Eye Res Inst, Singapore, Singapore..
    Gudnason, Vilmundur
    Iceland Heart Assoc, Kopavogur, Iceland..
    Guerrero, Ramiro
    Univ Icesi, Cali, Colombia..
    Guessous, Idris
    Univ Hosp Geneva, Geneva, Switzerland..
    Guimaraes, Andre L.
    Gulliford, Martin C.
    Kings Coll London, London WC2R 2LS, England..
    Gunnlaugsdottir, Johanna
    Guo, Xiu H.
    Capital Med Univ, Beijing, Peoples R China..
    Guo, Yin
    Capital Med Univ, Beijing, Peoples R China..
    Gupta, Prakash C.
    Healis Sekhsaria Inst Publ Hlth, New Delhi, India..
    Gureje, Oye
    Univ Ibadan, Ibadan, Nigeria..
    Gurzkowska, Beata
    Childrens Mem Hlth Inst, Warsaw, Poland..
    Gutierrez, Laura
    Inst Clin Effectiveness & Hlth Policy, Buenos Aires, DF, Argentina..
    Gutzwiller, Felix
    Univ Zurich, CH-8006 Zurich, Switzerland..
    Halkjaer, Jytte
    Danish Canc Soc Res Ctr, Lyngby, Denmark..
    Hardy, Rebecca
    UCL, London WC1E 6BT, England..
    Kumar, Rachakulla Hari
    Indian Council Med Res, New Delhi, India..
    Hayes, Alison J.
    Univ Sydney, Sydney, NSW 2006, Australia.;Tulane Univ, New Orleans, LA 70118 USA..
    He, Jiang
    Hendriks, Marleen Elisabeth
    Univ Amsterdam, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands..
    Hernandez Cadena, Leticia
    Natl Inst Publ Hlth, Mexicali, Baja California, Mexico..
    Heshmat, Ramin
    Hihtaniemi, Ilpo Tapani
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Ho, Sai Yin
    Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China..
    Ho, Suzanne C.
    Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China..
    Hobbs, Michael
    Univ Western Australia, Nedlands, WA 6009, Australia..
    Hofman, Albert
    Erasmus MC, Rotterdam, Netherlands..
    Hormiga, Claudia M.
    Horta, Bernardo L.
    Univ Fed Pelotas, Pelotas, Brazil..
    Houti, Leila
    Univ Oran 1, Oran, Algeria..
    Htay, Thein Thein
    Htet, Aung Soe
    Univ Oslo, N-0316 Oslo, Norway..
    Htike, Maung Maung Than
    Minist Hlth, Naypyidaw, Myanmar..
    Hu, Yonghua
    Peking Univ, Hlth Sci Ctr, Beijing, Peoples R China..
    Hussieni, Abdullatif S.
    Birzeit Univ, Bir Zayt, Israel..
    Huu, Chinh Nguyen
    Huybrechts, Inge
    Int Agcy Res Canc, Lyon, France..
    Hwalla, Nahla
    Amer Univ Beirut, Beirut, Lebanon..
    Iacoviello, Licia
    IRCCS Ist Neurol Mediterraneo Neuromed, Rome, Italy..
    Iannone, Anna G.
    Cardiol Mercato S Severino, Mercato San Severino, Italy..
    Ibrahim, M. Mohsen
    Cairo Univ, Cairo, Egypt..
    Ikram, M. Arfan
    Erasmus MC, Rotterdam, Netherlands..
    Irazola, Vilma E.
    Islam, Muhammad
    Aga Khan Univ, Lahore, Pakistan..
    Iwasaki, Masanori
    Niigata Univ, Niigata 95021, Japan..
    Jackson, Rod T.
    Univ Auckland, Auckland 1, New Zealand..
    Jacobs, Jeremy M.
    Hadassah Univ, Med Ctr, Tel Aviv, Israel..
    Jafar, Tazeen
    Duke NUS Grad Med Sch, Singapore, Singapore..
    Jamil, Kazi M.
    Kuwait Inst Scientifi c Res, Kuwait, Kuwait..
    Jamrozik, Konrad
    Univ Adelaide, Adelaide, SA 5005, Australia..
    Jasienska, Grazyna
    Jiang, Chao Qiang
    Guangzhou 12th Hosp, Guangzhou, Guangdong, Peoples R China..
    Joffres, Michel
    Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada..
    Johansson, Mattias
    Jonas, Jost B.
    Heidelberg Univ, Heidelberg, Germany..
    Jorgensen, Torben
    Joshi, Pradeep
    World Hlth Org Country Off, New Delhi, India..
    Juolevi, Anne
    Natl Inst Hlth & Welf, Espoo, Finland..
    Jurak, Gregor
    Univ Ljubljana, Ljubljana 61000, Slovenia..
    Juresa, Vesna
    Univ Zagreb, Zagreb 41000, Croatia..
    Kaaks, Rudolf
    German Canc Res Ctr, Berlin, Germany..
    Kafatos, Anthony
    Univ Crete, Iraklion, Greece..
    Kalter-Leibovici, Ofra
    Gertner Inst Epidemiol & Hlth Policy Res, Tel Aviv, Israel..
    Kapantais, Efthymios
    Hellen Med Assoc Obes, Iraklion, Greece..
    Kasaeian, Amir
    Noncommunicable Dis Res Ctr, Tehran, Iran..
    Katz, Joanne
    Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA..
    Kaur, Prabhdeep
    Natl Inst Epidemiol, Madras, Tamil Nadu, India..
    Kavousi, Maryam
    Erasmus MC, Rotterdam, Netherlands..
    Keil, Ulrich
    Univ Munster, Munster, Germany..
    Boker, Lital Keinan
    Univ Haifa, IL-31999 Haifa, Israel..
    Kelishadi, Roya
    Kemper, Han H. C. G.
    Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands..
    Kengne, Andre P.
    South African Med Res Council, Johannesburg, South Africa..
    Kersting, Mathilde
    Res Inst Child Nutr FKE, Munich, Germany..
    Key, Timothy
    Univ Oxford, Oxford OX1 2JD, England..
    Khader, Yousef Saleh
    Jordan Univ Sci & Technol, Amman, Jordan..
    Khalili, Davood
    Shahid Beheshti Univ Med Sci, Tehran, Iran..
    Khaw, Kay-Tee H.
    Univ Cambridge, Cambridge CB2 1TN, England..
    Khouw, Ilse M. S. L.
    FrieslandCampina, Singapore, Singapore..
    Kiechl, Stefan
    Med Univ Innsbruck, A-6020 Innsbruck, Austria..
    Killewo, Japhet
    Univ Hlth & Allied Sci, Tanza, Tanzania..
    Kim, Jeongseon
    Natl Canc Ctr, Seoul, South Korea..
    Kiyohara, Yutaka
    Kyushu Univ, Fukuoka 812, Japan..
    Klimont, Jeannette
    Stat Austria, Vienna, Austria..
    Kolle, Elin
    Norwegian Sch Sport Sci, Oslo, Norway..
    Kolsteren, Patrick
    Inst Trop Med, Brussels, Belgium..
    Korrovits, Paul
    Tartu Univ Clin, Tartu, Estonia..
    Koskinen, Seppo
    Kouda, Katsuyasu
    Kinki Univ, Fac Med, Higashiosaka, Osaka 577, Japan..
    Koziel, Slawomir
    Polish Acad Sci, Anthropol Unit, Wroclaw, Poland..
    Kratzer, Wolfgang
    Univ Hosp Ulm, Ulm, Germany..
    Krokstad, Steinar
    Norwegian Univ Sci & Technol, Oslo, Norway..
    Kromhout, Daan
    Wageningen Univ, NL-6700 AP Wageningen, Netherlands..
    Kruger, Herculina S.
    North West Univ, Johannesburg, South Africa..
    Kula, Krzysztof
    Med Univ Lodz, Lodz, Poland..
    Kulaga, Zbigniew
    Childrens Mem Hlth Inst, Warsaw, Poland..
    Kumar, R. Krishna
    Amrita Inst Med Sci, Kochi, India..
    Kusuma, Yadlapalli S.
    All India Inst Med Sci, New Delhi 110029, India..
    Kuulasmaa, Kari
    Laamiri, Fatima Zahra
    Univ Mohammed V Rabat, Rabat, Morocco..
    Laatikainen, Tiina
    Lachat, Carl
    Univ Ghent, B-9000 Ghent, Belgium..
    Laid, Youcef
    Lam, Tai Hing
    Landrove, Orlando
    Lanska, Vera
    Lappas, Georg
    Sahlgrens Acad, Stockholm, Sweden..
    Laugsand, Lars E.
    Norwegian Univ Sci & Technol, Oslo, Norway..
    Bao, Khanh Le Nguyen
    Le, Tuyen D.
    Natl Inst Nutr, Hanoi, Vietnam..
    Leclercq, Catherine
    Food & Agr Org, Rome, Italy..
    Lee, Jeannette
    Natl Univ Singapore, Singapore 117548, Singapore..
    Lee, Jeonghee
    Natl Canc Ctr, Seoul, South Korea..
    Lehtimaki, Terho
    Tampere Univ Hosp, Tampere, Finland..
    Lekhraj, Rampal
    Univ Putra Malaysia, Serdang 43400, Malaysia..
    Leon-Munoz, Luz M.
    Univ Autonoma Madrid, E-28049 Madrid, Spain..
    Lim, Wei-Yen
    Natl Univ Singapore, Singapore 117548, Singapore..
    Fernanda Lima-Costa, M.
    Fundacao Oswaldo Cruz, Rene Rachou Res Inst, Rio De Janeiro, Brazil..
    Lin, Xu
    Univ Chinese Acad Sci, Beijing, Peoples R China..
    Linneberg, Allan
    Res Ctr Prevent & Hlth, Aalborg, Denmark..
    Lissner, Lauren
    Gothenburg Univ, S-41124 Gothenburg, Sweden..
    Litwin, Mieczyslaw
    Childrens Mem Hlth Inst, Lodz, Poland..
    Liu, Jing
    Capital Med Univ, Beijing Anzhen Hosp, Beijing, Peoples R China..
    Lorbeer, Roberto
    Univ Med Greifswald, Greifswald, Germany..
    Lotufo, Paulo A.
    Univ Sao Paulo, BR-05508 Sao Paulo, Brazil..
    Eugenio Lozano, Jose
    Consejeria Sanidad Junta Castilla & Leon, Leon, Spain..
    Luksiene, Dalia
    Lithuanian Univ Hlth Sci, Kaunas, Lithuania..
    Lundqvist, Annamari
    Natl Inst Hlth & Welf, Tampere, Finland..
    Lunet, Nuno
    Univ Porto, Sch Med, Rua Campo Alegre 823, P-4100 Oporto, Portugal..
    Lytsy, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ma, Guansheng
    Peking Univ, Beijing 100871, Peoples R China..
    Machi, Suka
    Jikei Univ, Sch Med, Tokyo, Japan..
    Maggi, Stefania
    CNR, Pisa, Italy..
    Magliano, Dianna J.
    Baker IDI Heart & Diabet Inst, Melbourne, Vic, Australia..
    Makdisse, Marcia
    Hosp Israelita Albert Einstein, Sao Paulo, Brazil..
    Malekzadeh, Reza
    Univ Tehran Med Sci, Tehran, Iran..
    Malhotra, Rahul
    Duke NUS Grad Med Sch, Singapore, Singapore..
    Rao, Kodavanti Mallikharjuna
    Indian Council Med Res, New Delhi, India..
    Manios, Yannis
    Harokopio Univ Athens, Athens, Greece..
    Mann, Jim I.
    Univ Otago, Otaru, Hokkaido, Japan..
    Manzato, Enzo
    Univ Padua, I-35100 Padua, Italy..
    Margozzini, Paula
    Pontificia Univ Catolica Chile, Santiago, Chile..
    Markey, Oonagh
    Univ Reading, Reading RG6 2AH, Berks, England..
    Marques-Vidal, Pedro
    Univ Lausanne Hosp, Lausanne, Switzerland..
    Marrugat, Jaume
    Martin-Prevel, Yves
    Inst Rech Dev, Lyon, France..
    Martorell, Reynaldo
    Emory Univ, Atlanta, GA 30322 USA..
    Masoodi, Shariq R.
    Sherikashmir Inst Med Sci, Jammu, India..
    Matsha, Tandi E.
    Cape Peninsula Univ Technol, Cape Town, South Africa..
    Mazur, Artur
    Univ Rzeszow, Rzeszow, Poland..
    Mbanya, Jean Claude N.
    Univ Yaounde I, Yaounde, Cameroon..
    McFarlane, Shelly R.
    McGarvey, Stephen T.
    Brown Univ, Providence, RI 02912 USA..
    McKee, Martin
    London Sch Hyg & Trop Med, London, England..
    McLachlan, Stela
    Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland..
    McLean, Rachael M.
    McNulty, Breige A.
    Univ Coll Dublin, Dublin, Ireland..
    Yusof, Safiah Md
    Univ Teknol MARA, Serdang, Malaysia..
    Mediene-Benchekor, Sounnia
    Meirhaeghe, Aline
    Meisinger, Christa
    Helmholtz Zentrum mUNCHEN, Munich, Germany..
    Mendes, Larissa L.
    Univ Fed Juiz de Fora, Juiz De Fora, Brazil..
    Menezes, Ana Maria B.
    Mensink, Gert B. M.
    Robert Koch Inst, Berlin, Germany..
    Meshram, Indrapal I.
    Indian Council Med Res, New Delhi, India..
    Metspalu, Andres
    Univ Tartu, Ulikooli 18, EE-50090 Tartu, Estonia..
    Mi, Jie
    Capital Inst Pediat, Beijing, Peoples R China..
    Michaelsen, Kim F.
    Univ Copenhagen, DK-1168 Copenhagen, Denmark..
    Mikkel, Kairit
    Univ Tartu, Ulikooli 18, EE-50090 Tartu, Estonia..
    Miller, Jody C.
    Francisco Miquel, Juan
    Jaime Miranda, J.
    Univ Peruana Cayetano Heredia, Lima, Peru..
    Misigoj-Durakovic, Marjeta
    Univ Zagreb, Zagreb 41000, Croatia..
    Mohamed, Mostafa K.
    Ain Shams Univ, Cairo, Egypt..
    Mohammad, Kazem
    Univ Tehran Med Sci, Tehran, Iran..
    Mohammadifard, Noushin
    Isfahan Cardiovasc Res Ctr, Esfahan, Iran..
    Mohan, Viswanathan
    Madras Diabet Res Fdn, Madras, Tamil Nadu, India..
    Yusoff, Muhammad Fadhli Mohd
    Minist Hlth, Kuala Lumpur, Malaysia..
    Molbo, Drude
    Univ Copenhagen, DK-1168 Copenhagen, Denmark..
    Moller, Niels C.
    Univ Southern Denmark, Lyngby, Denmark..
    Molnar, Denes
    Univ Pecs, Pecs, Hungary..
    Mondo, Charles K.
    Mulago Hosp, Kampala, Uganda..
    Monterrubio, Eric A.
    Monyeki, Kotsedi Daniel K.
    Univ Limpopo, Limpopo, South Africa..
    Moreira, Leila B.
    Morejon, Alain
    Univ Med Sci, Havana, Cuba..
    Moreno, Luis A.
    Univ Zaragoza, E-50009 Zaragoza, Spain..
    Morgan, Karen
    RCSI Dublin, Dublin, Ireland..
    Mortensen, Erik Lykke
    Univ Copenhagen, DK-1168 Copenhagen, Denmark..
    Moschonis, George
    Harokopio Univ Athens, Athens, Greece..
    Mossakowska, Malgorzata
    Mota, Jorge
    Univ Porto, Rua Campo Alegre 823, P-4100 Oporto, Portugal..
    Motlagh, Mohammad Esmaeel
    Ahvaz Jundishapur Univ Med Sci, Tehran, Iran..
    Motta, Jorge
    Gorgas Mem Inst Publ Hlth, Panama City, Panama..
    Mu, Thet Thet
    Muiesan, Maria Lorenza
    Univ Brescia, I-25121 Brescia, Italy..
    Mueller-Nurasyid, Martina
    Helmholtz Zentrum mUNCHEN, Munich, Germany..
    Murphy, Neil
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Mursu, Jaakko
    Univ Eastern Finland, Joensuu, Finland..
    Murtagh, Elaine M.
    Mary Immaculate Coll, Limerick, Ireland..
    Musa, Kamarul Imran
    Univ Sains Malaysia, Kota Baharu, Malaysia..
    Musil, Vera
    Univ Zagreb, Zagreb 41000, Croatia..
    Nagel, Gabriele
    Univ Ulm, D-89069 Ulm, Germany..
    Nakamura, Harunobu
    Namesna, Jana
    Reg Author Publ Hlth, Banska Bystrica, Slovakia..
    Nang, Ei Ei K.
    Nangia, Vinay B.
    Suraj Eye Inst, Nagpur, Maharashtra, India..
    Nankap, Martin
    Helen Keller Int, Yaounde, Cameroon..
    Narake, Sameer
    Maria Navarrete-Munoz, Eva
    Nenko, Ilona
    Neovius, Martin
    Karolinska Inst, S-10401 Stockholm, Sweden..
    Nervi, Flavio
    Neuhauser, Hannelore K.
    Nguyen, Nguyen D.
    Univ Pharm & Med Ho Chi Minh City, Ho Chi Minh City, Vietnam..
    Nguyen, Quang Ngoc
    Nieto-Martinez, Ramfis E.
    Ning, Guang
    Shanghai Jiao Tong Univ, Sch Med, Shanghai 200030, Peoples R China..
    Ninomiya, Toshiharu
    Nishtar, Sania
    Heartfile, Karachi, Pakistan..
    Noale, Marianna
    Norat, Teresa
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Noto, Davide
    Univ Palermo, I-90133 Palermo, Italy..
    Al Nsour, Mohannad
    Eastern Mediterranean Publ Hlth Network, Amman, Jordan..
    O'Reilly, Dermot
    Ochoa-Aviles, Angelica M.
    Univ Cuenca, Cuenca, Ecuador..
    Oh, Kyungwon
    Korea Ctr Dis Control & Prevent, Seoul, South Korea..
    Olayan, Iman H.
    Kuwait Inst Sci Res, Kuwait, Kuwait..
    Anselmo Olinto, Maria Teresa
    Univ Vale Rio dos Sinos, Sao Leopoldo, RS, Brazil..
    Oltarzewski, Maciej
    Omar, Mohd A.
    Minist Hlth, Kuala Lumpur, Malaysia..
    Ordunez, Pedro
    Pan Amer Hlth Org, El Paso, TX USA..
    Ortiz, Ana P.
    Univ Puerto Rico, San Juan, PR USA..
    Osler, Merete
    Osmond, Clive
    MRC Lifecourse Epidemiol Unit, Southampton, Hants, England..
    Ostojic, Sergej M.
    Univ Novi Sad, Novi Sad 21000, Serbia..
    Otero, Johanna A.
    Overvad, Kim
    Aarhus Univ, DK-8000 Aarhus C, Denmark..
    Paccaud, Fred Michel
    Padez, Cristina
    Univ Coimbra, P-3000 Coimbra, Portugal..
    Pajak, Andrzej
    Palli, Domenico
    Palloni, Alberto
    Univ Madison Wisconsin, Madison, WI USA..
    Palmieri, Luigi
    Ist Super Sanita, Rome, Italy..
    Panda-Jonas, Songhomitra
    Panza, Francesco
    Univ Bari, I-70121 Bari, Italy..
    Parnell, Winsome R.
    Parsaeian, Mahboubeh
    Noncommunicable Dis Res Ctr, Tehran, Iran..
    Pednekar, Mangesh S.
    Peeters, Petra H.
    Univ Med Ctr Utrecht, Utrecht, Netherlands..
    Peixoto, Sergio Viana
    Pereira, Alexandre C.
    Heart Inst InCor, Sao Paulo, Brazil..
    Perez, Cynthia M.
    Peters, Annette
    Helmholtz Zentrum mUNCHEN, Munich, Germany..
    Peykari, Niloofar
    Noncommunicable Dis Res Ctr, Tehran, Iran..
    Pham, Son Thai
    Pigeot, Iris
    Leibniz Inst Prevent Res & Epidemiol BIPS, Leibniz, Germany..
    Pikhart, Hynek
    UCL, London WC1E 6BT, England..
    Pilav, Aida
    Fed Minist Hlth, Sarajevo, Bosnia & Herceg..
    Pilotto, Lorenza
    Pistelli, Francesco
    Univ Hosp Pisa, Pisa, Italy..
    Pitakaka, Freda
    Univ New S Wales, Sydney, NSW 2052, Australia..
    Piwonska, Aleksandra
    Cardinal Wyszynski Inst Cardiol, Warsaw, Poland..
    Piwonski, Jerzy
    Plans-Rubio, Pedro
    Poh, Bee Koon
    Publ Hlth Agcy Catalonia, Catalonia, Spain..
    Porta, Miquel
    Portegies, Marileen L. P.
    Erasmus MC, Rotterdam, Netherlands..
    Poulimeneas, Dimitrios
    Pradeepa, Rajendra
    Madras Diabet Res Fdn, Madras, Tamil Nadu, India..
    Prashant, Mathur
    Indian Council Med Res, New Delhi, India..
    Price, Jacqueline F.
    Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland..
    Puiu, Maria
    Victor Babes Univ Med & Pharm, Cluj Napoca, Romania..
    Punab, Margus
    Tartu Univ Clin, Tartu, Estonia..
    Qasrawi, Radwan F.
    Al Quds Univ, Jerusalem, Israel..
    Qorbani, Mostafa
    Alborz Univ Med Sci, Golestan, Iran..
    Bao, Tran Quoc
    Radic, Ivana
    Inst Publ Hlth Vojvodina, Vojvodina, Serbia..
    Radisauskas, Ricardas
    Lithuanian Univ Hlth Sci, Kaunas, Lithuania..
    Rahman, Mahmudur
    Inst Epidemiol Dis Control & Res, Dhaka, Bangladesh..
    Raitakari, Olli
    Turku Univ Hosp, FIN-20520 Turku, Finland..
    Raj, Manu
    Rao, Sudha Ramachandra
    Ramachandran, Ambady
    India Diabet Res Fdn, New Delhi, India..
    Ramke, Jacqueline
    Univ New S Wales, Sydney, NSW 2052, Australia..
    Ramos, Rafel
    Rampal, Sanjay
    Univ Malaya, Serdang, Malaysia..
    Rasmussen, Finn
    Redon, Josep
    Univ Valencia, E-46003 Valencia, Spain..
    Reganit, Paul Ferdinand M.
    Univ Philippines, Quezon City 1101, Philippines..
    Ribeiro, Robespierre
    Riboli, Elio
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Rigo, Fernando
    Hlth Ctr San Agustin, Madrid, Spain..
    de Wit, Tobias Floris Rinke
    PharmAccess Fdn, Groningen, Netherlands..
    Ritti-Dias, Raphael M.
    Rivera, Juan A.
    Robinson, Sian M.
    Univ Southampton, Southampton SO9 5NH, Hants, England..
    Robitaille, Cynthia
    Publ Hlth Agcy Canada, Montreal, PQ, Canada..
    Rodriguez-Artalejo, Fernando
    Univ Autonoma Madrid, E-28049 Madrid, Spain..
    del Cristo Rodriguez-Perez, Maria
    Canarian Hlth Serv, Madrid, Spain..
    Rodriguez-Villamizar, Laura A.
    Univ Ind Santander, Santander, Colombia..
    Rojas-Martinez, Rosalba
    Rojroongwasinkul, Nipa
    Mahidol Univ, Bangkok 10700, Thailand..
    Romaguera, Dora
    CIBEROBN, Madrid, Spain..
    Ronkainen, Kimmo
    Rosengren, Annika
    Gothenburg Univ, S-41124 Gothenburg, Sweden..
    Rouse, Ian
    Fiji Natl Univ, Nasinu, Fiji..
    Rubinstein, Adolfo
    Inst Clin Effectiveness & Hlth Policy, Buenos Aires, DF, Argentina..
    Ruehli, Frank J.
    Univ Zurich, CH-8006 Zurich, Switzerland..
    Rui, Ornelas
    Univ Madeira, Funchal, Portugal..
    Sandra Ruiz-Betancourt, Blanca
    Inst Mexicano Seguro Social, Rio Grande, Mexico..
    Russo Horimoto, Andrea R. V.
    Rutkowski, Marcin
    Med Univ Gdansk, Gdansk, Poland..
    Sabanayagam, Charumathi
    Singapore Eye Res Inst, Singapore, Singapore..
    Sachdev, Harshpal S.
    Sitaram Bhartia Inst Sci & Res, New Delhi, India..
    Saidi, Olfa
    Fac Med Tunis, Tunis, Tunisia..
    Salanave, Benoit
    French Inst Hlth Surveillance, Lyon, France..
    Salazar Martinez, Eduardo
    Salomaa, Veikko
    Salonen, Jukka T.
    Univ Helsinki, FIN-00014 Helsinki, Finland..
    Salvetti, Massimo
    Univ Brescia, I-25121 Brescia, Italy..
    Sanchez-Abanto, Jose
    Natl Inst Hlth, Lima, Peru..
    Sandjaja,
    Sans, Susana
    Catalan Dept Hlth, Madrid, Spain..
    Santos, Diana A.
    Univ Lisbon, P-1699 Lisbon, Portugal..
    Santos, Osvaldo
    dos Santos, Renata Nunes
    Univ Sao Paulo, BR-05508 Sao Paulo, Brazil..
    Santos, Rute
    Univ Porto, Rua Campo Alegre 823, P-4100 Oporto, Portugal..
    Sardinha, Luis B.
    Univ Lisbon, P-1699 Lisbon, Portugal..
    Sarrafzadegan, Nizal
    Saum, Kai-Uwe
    German Canc Res Ctr, Berlin, Germany..
    Savva, Savvas C.
    Res & Educ Inst Child Hlth, Nicosia, Cyprus..
    Scazufca, Marcia
    Univ Sao Paulo, BR-05508 Sao Paulo, Brazil..
    Rosario, Angelika Schaffrath
    Schargrodsky, Herman
    Hosp Italiano Buenos Aires, Buenos Aires, DF, Argentina..
    Schienkiewitz, Anja
    Schmidt, Ida Maria
    Rigshosp, Copenhagen, Denmark..
    Schneider, Ione J.
    Univ Fed Santa Catarina, BR-88040900 Florianopolis, SC, Brazil..
    Schultsz, Constance
    Univ Amsterdam, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands..
    Schutte, Aletta E.
    MRC North West Univ, Johannesburg, South Africa..
    Sein, Aye Aye
    Minist Hlth, Bangkok, Thailand..
    Senbanjo, Idowu O.
    Lagos State Univ, Coll Med, Lagos, Nigeria..
    Sepanlou, Sadaf G.
    Digest Dis Res Inst, Tehran, Iran..
    Shalnova, Svetlana A.
    Natl Res Ctr Prevent Med, Moscow, Russia..
    Shaw, Jonathan E.
    Shibuya, Kenji
    Univ Tokyo, Tokyo 1138654, Japan..
    Shin, Youchan
    Shiri, Rahman
    Finnish Inst Occupat Hlth, Espoo, Finland..
    Siantar, Rosalynn
    Sibai, Abla M.
    Silva, Antonio M.
    Univ Fed Maranhao, Sao Luis, Brazil.;Univ Fed Santa Catarina, BR-88040900 Florianopolis, SC, Brazil..
    Santos Silva, Diego Augusto
    Simon, Mary
    India Diabet Res Fdn, New Delhi, India..
    Simons, Judith
    St Vincents Hosp, Melbourne, Vic, Australia..
    Simons, Leon A.
    Sjostrom, Michael
    Slowikowska-Hilczer, Jolanta
    Med Univ Lodz, Lodz, Poland..
    Slusarczyk, Przemyslaw
    Smeeth, Liam
    London Sch Hyg & Trop Med, London, England..
    Smith, Margaret C.
    Univ Oxford, Oxford OX1 2JD, England..
    Snijder, Marieke B.
    So, Hung-Kwan
    Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China..
    Sobngwi, Eugene
    Univ Yaounde I, Yaounde, Cameroon..
    Soderberg, Stefan
    Umea Univ, S-90187 Umea, Sweden..
    Soekatri, Moesijanti Y. E.
    Hlth Polytech Inst, Bandung, Indonesia..
    Solfrizzi, Vincenzo
    Univ Bari, I-70121 Bari, Italy..
    Sonestedt, Emily
    Lund Univ, S-22100 Lund, Sweden..
    Sorensen, Thorkild I. A.
    Univ Copenhagen, DK-1168 Copenhagen, Denmark..
    Soric, Maroje
    Univ Zagreb, Zagreb 41000, Croatia..
    Jerome, Charles Sossa
    Soumare, Aicha
    Univ Bordeaux, Bordeaux, France..
    Staessen, Jan A.
    Univ Leuven, Leuven, Belgium..
    Starc, Gregor
    Stathopoulou, Maria G.
    INSERM, F-75654 Paris 13, France..
    Staub, Kaspar
    Univ Zurich, CH-8006 Zurich, Switzerland..
    Stavreski, Bill
    Heart Fdn, Sydney, NSW, Australia..
    Steene-Johannessen, Jostein
    Norwegian Sch Sport Sci, Oslo, Norway..
    Stehle, Peter
    Univ Bonn, Bonn, Germany..
    Stein, Aryeh D.
    Emory Univ, Atlanta, GA 30322 USA..
    Stergiou, George S.
    Sotiria Hosp, Athina, Greece..
    Stessman, Jochanan
    Stieber, Jutta
    Helmholtz Zentrum mUNCHEN, Munich, Germany..
    Stoeckl, Doris
    Helmholtz Zentrum mUNCHEN, Munich, Germany..
    Stocks, Tanja
    Stokwiszewski, Jakub
    Natl Inst Hyg, Natl Inst Publ Hlth, Warsaw, Poland..
    Stratton, Gareth
    Swansea Univ, Swansea, W Glam, Wales..
    Strufaldi, Maria Wany
    Sun, Chien-An
    Fu Jen Catholic Univ, Taipei, Taiwan..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sung, Yn-Tz
    Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China..
    Sunyer, Jordi
    Ctr Res Environm Epidemiol, Madrid, Spain..
    Suriyawongpaisal, Paibul
    Mahidol Univ, Bangkok 10700, Thailand..
    Swinburn, Boyd A.
    Univ Auckland, Auckland 1, New Zealand..
    Sy, Rody G.
    Univ Philippines, Quezon City 1101, Philippines..
    Szponar, Lucjan
    Natl Food & Nutr Inst, Warsaw, Poland..
    Tai, E. Shyong
    Natl Univ Singapore, Singapore 117548, Singapore..
    Tammesoo, Mari-Liis
    Univ Tartu, Ulikooli 18, EE-50090 Tartu, Estonia..
    Tamosiunas, Abdonas
    Lithuanian Univ Hlth Sci, Kaunas, Lithuania..
    Tang, Line
    Res Ctr Prevent & Hlth, Odense, Denmark..
    Tang, Xun
    Peking Univ, Hlth Sci Ctr, Beijing 100871, Peoples R China..
    Tanser, Frank
    Univ KwaZulu Natal, Durban, South Africa..
    Tao, Yong
    Peking Univ, Beijing 100871, Peoples R China..
    Tarp, Jakob
    Univ Southern Denmark, Lyngby, Denmark..
    Tarqui-Mamani, Carolina B.
    Natl Inst Hlth, Lima, Peru..
    Taylor, Anne
    Univ Adelaide, Adelaide, SA 5005, Australia..
    Tchibindat, Felicite
    UNICEF, Yaounde, Cameroon..
    Thijs, Lutgarde
    Thuesen, Betina H.
    Tjonneland, Anne
    Danish Canc Soc Res Ctr, Odense, Denmark..
    Tolonen, Hanna K.
    Tolstrup, Janne S.
    Univ Southern Denmark, Lyngby, Denmark..
    Topbas, Murat
    Karadeniz Tech Univ, Ankara, Turkey..
    Topor-Madry, Roman
    Jagiellonian Univ, Coll Med, PL-31007 Krakow, Poland..
    Torrent, Maties
    Traissac, Pierre
    Inst Rech Dev, Lyon, France..
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA.;Alexander Technol Educ Inst, Athens, Greece..
    Trinh, Oanh T. H.
    Trivedi, Atul
    Govt Med Coll, New Delhi, India..
    Tshepo, Lechaba
    Sefako Makgatho Hlth Sci Univ, Johannesburg, South Africa..
    Tulloch-Reid, Marshall K.
    Tuomainen, Tomi-Pekka
    Tuomilehto, Jaakko
    Dasman Diabet Inst, Kuwait, Kuwait. Minist Hlth, Hamilton, New Zealand..
    Tynelius, Per
    Karolinska Inst, S-10401 Stockholm, Sweden..
    Tzotzas, Themistoklis
    Hellen Med Assoc Obes, Athens, Greece..
    Tzourio, Christophe
    Univ Bordeaux, Bordeaux, France..
    Ueda, Peter
    Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA..
    Ukoli, Flora A. M.
    Meharry Med Coll, Nashville, TN USA..
    Ulmer, Hanno
    Med Univ Innsbruck, A-6020 Innsbruck, Austria..
    Unal, Belgin
    Dokuz Eylul Univ, TR-35210 Alsancak, Turkey..
    Valdivia, Gonzalo
    Vale, Susana
    Univ Porto, Rua Campo Alegre 823, P-4100 Oporto, Portugal..
    Valvi, Damaskini
    Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA..
    van der Schouw, Yvonne T.
    Univ Med Ctr Utrecht, Utrecht, Netherlands..
    Van Herck, Koen
    Univ Ghent, B-9000 Ghent, Belgium..
    Minh, Hoang Van
    van Valkengoed, Irene G. M.
    Univ Amsterdam, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands..
    Vanderschueren, Dirk
    Katholieke Univ Leuven, Louvain, Belgium..
    Vanuzzo, Diego
    Ctr Prevenz Cardiovasc Udine, Udine, Italy..
    Vatten, Lars
    Vega, Tomas
    Velasquez-Melendez, Gustavo
    Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil..
    Veronesi, Giovanni
    Univ Insubria, Varese, Italy..
    Verschuren, W. M. Monique
    Natl Inst Publ Hlth & Environm, Amsterdam, Netherlands..
    Viegi, Giovanni
    Viet, Lucie
    Natl Inst Publ Hlth & Environm, Amsterdam, Netherlands..
    Viikari-Juntura, Eira
    Finnish Inst Occupat Hlth, Helsinki, Finland..
    Vineis, Paolo
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Vioque, Jesus
    Univ Miguel Hernandez, Madrid, Spain..
    Virtanen, Jyrki K.
    Visvikis-Siest, Sophie
    INSERM, F-75654 Paris 13, France..
    Viswanathan, Bharathi
    Minist Hlth, Victoria, Seychelles..
    Vollenweider, Peter
    Univ Lausanne Hosp, Lausanne, Switzerland..
    Voutilainen, Sari
    Vrijheid, Martine
    Ctr Res Environm Epidemiol, Madrid, Spain..
    Wade, Alisha N.
    Univ Witwatersrand, ZA-2050 Johannesburg, South Africa..
    Wagner, Aline
    Univ Strasbourg, Strasbourg, France..
    Walton, Janette
    Univ Coll Cork, Cork, Ireland..
    Mohamud, Wan Nazaimoon Wan
    Inst Med Res, Serdang, Malaysia..
    Wang, Ming-Dong
    Wang, Qian
    Xinjiang Med Univ, Xinjiang, Peoples R China..
    Wang, Ya Xing
    Beijing Tongren Hosp, Beijing, Peoples R China..
    Wannamethee, S. Goya
    UCL, London WC1E 6BT, England..
    Wareham, Nicholas
    Univ Cambridge, Cambridge CB2 1TN, England..
    Weerasekera, Deepa
    Minist Hlth, Hamilton, New Zealand..
    Whincup, Peter H.
    Univ London, London WC1E 7HU, England..
    Widhalm, Kurt
    Med Univ Vienna, Vienna, Austria..
    Widyahening, Indah S.
    Univ Indonesia, Bandung, Indonesia..
    Wiecek, Andrzej
    Med Univ Silesia, Katowice, Poland..
    Wilks, Rainford J.
    Willeit, Johann
    Med Univ Innsbruck, A-6020 Innsbruck, Austria..
    Wojtyniak, Bogdan
    Wong, Jyh Eiin
    Univ Kebangsaan Malaysia, Bangi 43600, Malaysia..
    Wong, Tien Yin
    Duke NUS Grad Med Sch, Singapore, Singapore..
    Woo, Jean
    Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China..
    Woodward, Mark
    Univ Sydney, Sydney, NSW 2006, Australia.;Univ Oxford, Oxford OX1 2JD, England..
    Wu, Frederick C.
    Univ Manchester, Manchester M13 9PL, Lancs, England..
    Wu, JianFeng
    Shandong Univ Tradit Chinese Med, Jinan, Peoples R China..
    Wu, Shou Ling
    Kailuan Gen Hosp, Beijing, Peoples R China..
    Xu, Haiquan
    Minist Agr, Inst Food & Nutr Dev, Beijing, Peoples R China..
    Xu, Liang
    Capital Med Univ, Beijing, Peoples R China..
    Yamborisut, Uruwan
    Mahidol Univ, Bangkok 10700, Thailand..
    Yan, Weili
    Fudan Univ, Shanghai, Peoples R China..
    Yang, Xiaoguang
    Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China..
    Yardim, Nazan
    Minist Hlth, Ankara, Turkey..
    Ye, Xingwang
    Univ Chinese Acad Sci, Beijing, Peoples R China..
    Yiallouros, Panayiotis K.
    Cyprus Univ Technol, Limassol, Cyprus..
    Yoshihara, Akihiro
    Niigata Univ, Niigata 95021, Japan..
    You, Qi Sheng
    Younger-Coleman, Novie O.
    Yusoff, Ahmad F.
    Minist Hlth, Kuala Lumpur, Malaysia..
    Zainuddin, Ahmad A.
    Univ Teknol MARA, Serdang, Malaysia..
    Zambon, Sabina
    Univ Padua, I-35100 Padua, Italy..
    Zdrojewski, Tomasz
    Med Univ Gdansk, Gdansk, Poland..
    Zeng, Yi
    Duke Univ, Durham, NC 27706 USA.;Peking Univ, Beijing 100871, Peoples R China..
    Zhao, Dong
    Capital Med Univ, Beijing Anzhen Hosp, Beijing, Peoples R China..
    Zhao, Wenhua
    Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China..
    Zheng, Yingfeng
    Singapore Eye Res Inst, Singapore, Singapore..
    Zhou, Maigeng
    Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China..
    Zhu, Dan
    Inner Mongolia Med Univ, Inner Mongolia, Peoples R China..
    Zimmermann, Esther
    Bispebjerg Hosp, Copenhagen, Denmark.;Frederiksberg Univ Hosp, Frederiksberg, Denmark..
    Zuniga Cisneros, Julio
    Gorgas Mem Inst Publ Hlth, Panama City, Panama..
    Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants2016In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 387, no 10026, p. 1377-1396Article in journal (Refereed)
    Abstract [en]

    Background Underweight and severe and morbid obesity are associated with highly elevated risks of adverse health outcomes. We estimated trends in mean body-mass index (BMI), which characterises its population distribution, and in the prevalences of a complete set of BMI categories for adults in all countries.

    Methods We analysed, with use of a consistent protocol, population-based studies that had measured height and weight in adults aged 18 years and older. We applied a Bayesian hierarchical model to these data to estimate trends from 1975 to 2014 in mean BMI and in the prevalences of BMI categories (<18.5 kg/m(2) [underweight], 18.5 kg/m(2) to <20 kg/m(2), 20 kg/m(2) to <25 kg/m(2), 25 kg/m(2) to <30 kg/m(2), 30 kg/m(2) to <35 kg/m(2), 35 kg/m(2) to <40 kg/m(2), = 40 kg/m(2) [morbid obesity]), by sex in 200 countries and territories, organised in 21 regions. We calculated the posterior probability of meeting the target of halting by 2025 the rise in obesity at its 2010 levels, if post-2000 trends continue.

    Findings We used 1698 population-based data sources, with more than 19.2 million adult participants (9.9 million men and 9.3 million women) in 186 of 200 countries for which estimates were made. Global age-standardised mean BMI increased from 21.7 kg/m(2) (95% credible interval 21.3-22.1) in 1975 to 24.2 kg/m(2) (24.0-24.4) in 2014 in men, and from 22.1 kg/m(2) (21.7-22.5) in 1975 to 24.4 kg/m(2) (24.2-24.6) in 2014 in women. Regional mean BMIs in 2014 for men ranged from 21.4 kg/m(2) in central Africa and south Asia to 29.2 kg/m(2) (28.6-29.8) in Polynesia and Micronesia; for women the range was from 21.8 kg/m(2) (21.4-22.3) in south Asia to 32.2 kg/m(2) (31.5-32.8) in Polynesia and Micronesia. Over these four decades, age-standardised global prevalence of underweight decreased from 13.8% (10.5-17.4) to 8.8% (7.4-10.3) in men and from 14.6% (11.6-17.9) to 9.7% (8.3-11.1) in women. South Asia had the highest prevalence of underweight in 2014, 23.4% (17.8-29.2) in men and 24.0% (18.9-29.3) in women. Age-standardised prevalence of obesity increased from 3.2% (2.4-4.1) in 1975 to 10.8% (9.7-12.0) in 2014 in men, and from 6.4% (5.1-7.8) to 14.9% (13.6-16.1) in women. 2.3% (2.0-2.7) of the world's men and 5.0% (4.4-5.6) of women were severely obese (ie, have BMI = 35 kg/m(2)). Globally, prevalence of morbid obesity was 0.64% (0.46-0.86) in men and 1.6% (1.3-1.9) in women.

    Interpretation If post-2000 trends continue, the probability of meeting the global obesity target is virtually zero. Rather, if these trends continue, by 2025, global obesity prevalence will reach 18% in men and surpass 21% in women; severe obesity will surpass 6% in men and 9% in women. Nonetheless, underweight remains prevalent in the world's poorest regions, especially in south Asia.

  • 98. Dimas, Antigone S.
    et al.
    Lagou, Vasiliki
    Barker, Adam
    Knowles, Joshua W.
    Maegi, Reedik
    Hivert, Marie-France
    Benazzo, Andrea
    Rybin, Denis
    Jackson, Anne U.
    Stringham, Heather M.
    Song, Ci
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Fischer-Rosinsky, Antje
    Boesgaard, Trine Wellov
    Grarup, Niels
    Abbasi, Fahim A.
    Assimes, Themistocles L.
    Hao, Ke
    Yang, Xia
    Lecoeur, Cecile
    Barroso, Ines
    Bonnycastle, Lori L.
    Boettcher, Yvonne
    Bumpstead, Suzannah
    Chines, Peter S.
    Erdos, Michael R.
    Graessler, Jurgen
    Kovacs, Peter
    Morken, Mario A.
    Narisu, Narisu
    Payne, Felicity
    Stancakova, Alena
    Swift, Amy J.
    Toenjes, Anke
    Bornstein, Stefan R.
    Cauchi, Stephane
    Froguel, Philippe
    Meyre, David
    Schwarz, Peter E. H.
    Haering, Hans-Ulrich
    Smith, Ulf
    Boehnke, Michael
    Bergman, Richard N.
    Collins, Francis S.
    Mohlke, Karen L.
    Tuomilehto, Jaakko
    Quertemous, Thomas
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Hansen, Torben
    Pedersen, Oluf
    Walker, Mark
    Pfeiffer, Andreas F. H.
    Spranger, Joachim
    Stumvoll, Michael
    Meigs, James B.
    Wareham, Nicholas J.
    Kuusisto, Johanna
    Laakso, Markku
    Langenberg, Claudia
    Dupuis, Josee
    Watanabe, Richard M.
    Florez, Jose C.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    McCarthy, Mark I.
    Prokopenko, Inga
    Impact of Type 2 Diabetes Susceptibility Variants on Quantitative Glycemic Traits Reveals Mechanistic Heterogeneity2014In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 63, no 6, p. 2158-2171Article in journal (Refereed)
    Abstract [en]

    Patients with established type 2 diabetes display both beta-cell dysfunction and insulin resistance. To define fundamental processes leading to the diabetic state, we examined the relationship between type 2 diabetes risk variants at 37 established susceptibility loci, and indices of proinsulin processing, insulin secretion, and insulin sensitivity. We included data from up to 58,614 nondiabetic subjects with basal measures and 17,327 with dynamic measures. We used additive genetic models with adjustment for sex, age, and BMI, followed by fixed-effects, inverse-variance meta-analyses. Cluster analyses grouped risk loci into five major categories based on their relationship to these continuous glycemic phenotypes. The first cluster (PPARG, KLF14, IRS1, GCKR) was characterized by primary effects on insulin sensitivity. The second cluster (MTNR1B, GCK) featured risk alleles associated with reduced insulin secretion and fasting hyperglycemia. ARAP1 constituted a third cluster characterized by defects in insulin processing. A fourth cluster (TCF712, SLC30A8, HHEX/IDE, CDKAL1, CDKN2A/2B) was defined by loci influencing insulin processing and secretion without a detectable change in fasting glucose levels. The final group contained 20 risk loci with no clear-cut associations to continuous glycemic traits. By assembling extensive data on continuous glycemic traits, we have exposed the diverse mechanisms whereby type 2 diabetes risk variants impact disease predisposition.

  • 99. Do, Ron
    et al.
    Willer, Cristen J.
    Schmidt, Ellen M.
    Sengupta, Sebanti
    Gao, Chi
    Peloso, Gina M.
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kanoni, Stavroula
    Ganna, Andrea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Chen, Jin
    Buchkovich, Martin L.
    Mora, Samia
    Beckmann, Jacques S.
    Bragg-Gresham, Jennifer L.
    Chang, Hsing-Yi
    Demirkan, Ayse
    Den Hertog, Heleen M.
    Donnelly, Louise A.
    Ehret, Georg B.
    Esko, Tonu
    Feitosa, Mary F.
    Ferreira, Teresa
    Fischer, Krista
    Fontanillas, Pierre
    Fraser, Ross M.
    Freitag, Daniel F.
    Gurdasani, Deepti
    Heikkila, Kauko
    Hyppoenen, Elina
    Isaacs, Aaron
    Jackson, Anne U.
    Johansson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Johnson, Toby
    Kaakinen, Marika
    Kettunen, Johannes
    Kleber, Marcus E.
    Li, Xiaohui
    Luan, Jian'an
    Lyytikainen, Leo-Pekka
    Magnusson, Patrik K. E.
    Mangino, Massimo
    Mihailov, Evelin
    Montasser, May E.
    Mueller-Nurasyid, Martina
    Nolte, Ilja M.
    O'Connell, Jeffrey R.
    Palmer, Cameron D.
    Perola, Markus
    Petersen, Ann-Kristin
    Sanna, Serena
    Saxena, Richa
    Service, Susan K.
    Shah, Sonia
    Shungin, Dmitry
    Sidore, Carlo
    Song, Ci
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Strawbridge, Rona J.
    Surakka, Ida
    Tanaka, Toshiko
    Teslovich, Tanya M.
    Thorleifsson, Gudmar
    Van den Herik, Evita G.
    Voight, Benjamin F.
    Volcik, Kelly A.
    Waite, Lindsay L.
    Wong, Andrew
    Wu, Ying
    Zhang, Weihua
    Absher, Devin
    Asiki, Gershim
    Barroso, Ines
    Been, Latonya F.
    Bolton, Jennifer L.
    Bonnycastle, Lori L.
    Brambilla, Paolo
    Burnett, Mary S.
    Cesana, Giancarlo
    Dimitriou, Maria
    Doney, Alex S. F.
    Doering, Angela
    Elliott, Paul
    Epstein, Stephen E.
    Eyjolfsson, Gudmundur Ingi
    Gigante, Bruna
    Goodarzi, Mark O.
    Grallert, Harald
    Gravito, Martha L.
    Groves, Christopher J.
    Hallmans, Goran
    Hartikainen, Anna-Liisa
    Hayward, Caroline
    Hernandez, Dena
    Hicks, Andrew A.
    Holm, Hilma
    Hung, Yi-Jen
    Illig, Thomas
    Jones, Michelle R.
    Kaleebu, Pontiano
    Kastelein, John J. P.
    Khaw, Kay-Tee
    Kim, Eric
    Klopp, Norman
    Komulainen, Pirjo
    Kumari, Meena
    Langenberg, Claudia
    Lehtimaki, Terho
    Lin, Shih-Yi
    Lindstrom, Jaana
    Loos, Ruth J. F.
    Mach, Francois
    McArdle, Wendy L.
    Meisinger, Christa
    Mitchell, Braxton D.
    Mueller, Gabrielle
    Nagaraja, Ramaiah
    Narisu, Narisu
    Nieminen, Tuomo V. M.
    Nsubuga, Rebecca N.
    Olafsson, Isleifur
    Ong, Ken K.
    Palotie, Aarno
    Papamarkou, Theodore
    Pomilla, Cristina
    Pouta, Anneli
    Rader, Daniel J.
    Reilly, Muredach P.
    Ridker, Paul M.
    Rivadeneira, Fernando
    Rudan, Igor
    Ruokonen, Aimo
    Samani, Nilesh
    Scharnagl, Hubert
    Seeley, Janet
    Silander, Kaisa
    Stancakova, Alena
    Stirrups, Kathleen
    Swift, Amy J.
    Tiret, Laurence
    Uitterlinden, Andre G.
    van Pelt, L. Joost
    Vedantam, Sailaja
    Wainwright, Nicholas
    Wijmenga, Cisca
    Wild, Sarah H.
    Willemsen, Gonneke
    Wilsgaard, Tom
    Wilson, James F.
    Young, Elizabeth H.
    Zhao, Jing Hua
    Adair, Linda S.
    Arveiler, Dominique
    Assimes, Themistocles L.
    Bandinelli, Stefania
    Bennett, Franklyn
    Bochud, Murielle
    Boehm, Bernhard O.
    Boomsma, Dorret I.
    Borecki, Ingrid B.
    Bornstein, Stefan R.
    Bovet, Pascal
    Burnier, Michel
    Campbell, Harry
    Chakravarti, Aravinda
    Chambers, John C.
    Chen, Yii-Der Ida
    Collins, Francis S.
    Cooper, Richard S.
    Danesh, John
    Dedoussis, George
    de Faire, Ulf
    Feranil, Alan B.
    Ferrieres, Jean
    Ferrucci, Luigi
    Freimer, Nelson B.
    Gieger, Christian
    Groop, Leif C.
    Gudnason, Vilmundur
    Gyllensten, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hamsten, Anders
    Harris, Tamara B.
    Hingorani, Aroon
    Hirschhorn, Joel N.
    Hofman, Albert
    Hovingh, G. Kees
    Hsiung, Chao Agnes
    Humphries, Steve E.
    Hunt, Steven C.
    Hveem, Kristian
    Iribarren, Carlos
    Jarvelin, Marjo-Riitta
    Jula, Antti
    Kahonen, Mika
    Kaprio, Jaakko
    Kesaniemi, Antero
    Kivimaki, Mika
    Kooner, Jaspal S.
    Koudstaal, Peter J.
    Krauss, Ronald M.
    Kuh, Diana
    Kuusisto, Johanna
    Kyvik, Kirsten O.
    Laakso, Markku
    Lakka, Timo A.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lindgren, Cecilia M.
    Martin, Nicholas G.
    Maerz, Winfried
    McCarthy, Mark I.
    McKenzie, Colin A.
    Meneton, Pierre
    Metspalu, Andres
    Moilanen, Leena
    Morris, Andrew D.
    Munroe, Patricia B.
    Njolstad, Inger
    Pedersen, Nancy L.
    Power, Chris
    Pramstaller, Peter P.
    Price, Jackie F.
    Psaty, Bruce M.
    Quertermous, Thomas
    Rauramaa, Rainer
    Saleheen, Danish
    Salomaa, Veikko
    Sanghera, Dharambir K.
    Saramies, Jouko
    Schwarz, Peter E. H.
    Sheu, Wayne H-H
    Shuldiner, Alan R.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Spector, Tim D.
    Stefansson, Kari
    Strachan, David P.
    Tayo, Bamidele O.
    Tremoli, Elena
    Tuomilehto, Jaakko
    Uusitupa, Matti
    van Duijn, Cornelia M.
    Vollenweider, Peter
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Wareham, Nicholas J.
    Whitfield, John B.
    Wolffenbuttel, Bruce H. R.
    Altshuler, David
    Ordovas, Jose M.
    Boerwinkle, Eric
    Palmer, Colin N. A.
    Thorsteinsdottir, Unnur
    Chasman, Daniel I.
    Rotter, Jerome I.
    Franks, Paul W.
    Ripatti, Samuli
    Cupples, L. Adrienne
    Sandhu, Manjinder S.
    Rich, Stephen S.
    Boehnke, Michael
    Deloukas, Panos
    Mohlke, Karen L.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Abecasis, Goncalo R.
    Daly, Mark J.
    Neale, Benjamin M.
    Kathiresan, Sekar
    Common variants associated with plasma triglycerides and risk for coronary artery disease2013In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, no 11, p. 1345-+Article in journal (Refereed)
    Abstract [en]

    Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.

  • 100.
    Dumanski, Jan P.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lambert, Jean-Charles
    Univ Lille, INSERM, CHU Lille, Pasteur Lille,U1167,RID AGE Risk Factors & Mol De, F-59000 Lille, France..
    Rasi, Chiara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Davies, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Grenier-Boley, Benjamin
    Univ Lille, INSERM, CHU Lille, Pasteur Lille,U1167,RID AGE Risk Factors & Mol De, F-59000 Lille, France..
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Broad Inst MIT, Cambridge, MA 02142 USA.;Harvard Univ, Cambridge, MA 02142 USA..
    Campion, Dominique
    Rouen Univ Hosp, INSERM, CNR MAJ, U1079, F-76031 Rouen, France..
    Dufouil, Carole
    Victor Segalen Univ, INSERM, U708, F-33076 Bordeaux, France..
    Pasquier, Florence
    Univ Lille, CNR MAJ, Inserm 1171, F-59000 Lille, France.;CHU Lille, F-59000 Lille, France..
    Amouyel, Philippe
    Univ Lille, INSERM, CHU Lille, Pasteur Lille,U1167,RID AGE Risk Factors & Mol De, F-59000 Lille, France..
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Forsberg, Lars A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mosaic Loss of Chromosome Y in Blood Is Associated with Alzheimer Disease2016In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 98, no 6, p. 1208-1219Article in journal (Refereed)
    Abstract [en]

    Men have a shorter life expectancy compared with women but the underlying factor(s) are not clear. Late-onset, sporadic Alzheimer disease (AD) is a common and lethal neurodegenerative disorder and many germline inherited variants have been found to influence the risk of developing AD. Our previous results show that a fundamentally different genetic variant, i.e., lifetime-acquired loss of chromosome Y (LOY) in blood cells, is associated with all-cause mortality and an increased risk of non-hematological tumors and that LOY could be induced by tobacco smoking. We tested here a hypothesis that men with LOY are more susceptible to AD and show that LOY is associated with AD in three independent studies of different types. In a case-control study, males with AD diagnosis had higher degree of LOY mosaicism (adjusted odds ratio = 2.80, p = 0.0184, AD events = 606). Furthermore, in two prospective studies, men with LOY at blood sampling had greater risk for incident AD diagnosis during follow-up time (hazard ratio [HR] = 6.80, 95% confidence interval [95% CI] = 2.16-21.43, AD events = 140, p = 0.0011). Thus, LOY in blood is associated with risks of both AD and cancer, suggesting a role of LOY in blood cells on disease processes in other tissues, possibly via defective immunosurveillance. As a male-specific risk factor, LOY might explain why males on average live shorter lives than females.

    Download full text (pdf)
    fulltext
1234567 51 - 100 of 514
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf