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  • 1.
    Ahlström, Tommy
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Rudberg, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Correlation between plasma calcium, parathyroid hormone (PTH) and the metabolic syndrome (MetS) in a community-based cohort of men and women2009In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 71, no 5, p. 673-678Article in journal (Refereed)
    Abstract [en]

    CONTEXT: In recent years, an association has been noted between several abnormalities that characterize the metabolic syndrome (MetS) and primary hyperparathyroidism (pHPT). These abnormalities include dyslipidaemia, obesity, insulin resistance and hypertension. The correlations between plasma calcium, parathyroid hormone (PTH) and the variables in the MetS in a normal population are still unclear.

    OBJECTIVE: To describe correlations between plasma calcium and PTH and the various abnormalities present in the MetS in a healthy population.

    DESIGN: We studied 1016 healthy individuals from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) population of 70 years old, by means of plasma analyses of calcium, PTH, creatinine, lipids, insulin and glucose, as well as by standardized blood pressure measurements. Further, body mass index (BMI) and waist circumference were determined.

    RESULTS: The more National Cholesterol Education Program (NCEP) criteria for the MetS that were met, the higher the s-PTH and albumin-corrected s-calcium. Further, positive correlations between plasma calcium and BMI (P = 0.0003), waist circumference (P = 0.0009) and insulin resistance (P = 0.079) were found. PTH and BMI (P < 0.0001), waist circumference (P < 0.0001), systolic blood pressure (P = 0.0034), diastolic blood pressure (P = 0.0008), serum triglycerides (P = 0.0003) and insulin resistance (P = 0.0003) were positively correlated, whereas serum high density lipoproteins (HDL) (P = 0.036) and PTH were negatively correlated.

    CONCLUSIONS: We conclude that PTH correlates with several of the metabolic factors included in the MetS within a normocalcaemic population. In addition, individuals with mild pHPT present significantly more NCEP criteria for MetS. We postulate that increased levels of PTH in pHPT may be associated with the increased cardiovascular morbidity and mortality seen in pHPT.

  • 2. Alsén, Martin
    et al.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Eggers, Kai
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    »HEART score« – lösningen på säker handläggning av patienter med misstänkt akut kranskärlsjukdom på akutmottagningen?: ["HEART score"--the solution for secure management of patients with suspected acute coronary syndrome in the emergency department?]2013In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 110, no 27-28, p. 1297-Article in journal (Other academic)
  • 3.
    Bhatt, Deepak L.
    et al.
    Harvard Med Sch, Brigham & Womens Hosp, Heart & Vasc Ctr, 75 Francis St, Boston, MA 02115 USA.
    Fox, Kim
    Imperial Coll, Natl Heart & Lung Inst, London, England;Royal Brompton Hosp, London, England.
    Harrington, Robert A.
    Stanford Univ, Dept Med, SCCR, Stanford, CA 94305 USA.
    Leiter, Lawrence A.
    Univ Toronto, St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON, Canada.
    Mehta, Shamir R.
    Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada;McMaster Univ, Hamilton, ON, Canada.
    Simon, Tabassome
    Sorbonne Univ Paris, Hop St Antoine, AP HP, Dept Clin Pharmacol URCEST, Paris, France.
    Andersson, Marielle
    AstraZeneca Gothenburg, Dept Cardiovasc Renal & Metab, Molndal, Sweden.
    Himmelmann, Anders
    AstraZeneca Gothenburg, Dept Cardiovasc Renal & Metab, Molndal, Sweden.
    Ridderstrale, Wilhelm
    AstraZeneca Gothenburg, Dept Cardiovasc Renal & Metab, Molndal, Sweden.
    Held, Claes
    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. Uppsala Univ, Uppsala Clin Res Ctr, Dept Med Sci, Cardiol, Uppsala, Sweden.
    Steg, Philippe Gabriel
    Univ Paris Diderot, Hop Bichat, AP HP, Dept Hosp Univ FIRE,F CRIN Network,FACT, Paris, France;Univ Paris Diderot, Hop Bichat, AP HP, Dept Hosp Univ FIRE,INSERM,U 1148, Paris, France;Imperial Coll, Royal Brompton Hosp, NHLI, London, England.
    Steg, Gabriel
    Diaz, Rafael
    Amerena, John
    Huber, Kurt
    Sinnaeve, Peter
    Nicolau, Jose Carlos
    Kerr Saraiva, Jose Francisco
    Petrov, Ivo
    Corbalan, Ramon
    Ge, Junbo
    Zhao, Qiang
    Botero, Rodrigo
    Widimsky, Petr
    Kristensen, Steen Dalby
    Hartikainen, Juha
    Danchin, Nicolas
    Darius, Harald
    Fat, Tse Hung
    Kiss, Robert Gabor
    Pais, Prem
    Lev, Eli
    De Luca, Leonardo
    Goto, Shinya
    Ramos Lopez, Gabriel Arturo
    Cornel, Jan Hein
    Kontny, Frederic
    Medina, Felix
    Babilonia, Noe
    Opolski, Grzegorz
    Vinereanu, Dragos
    Zateyshchikov, Dmitry
    Ruda, Mikhail
    Elamin, Omer
    Kovar, Frantisek
    Dalby, Anthony John
    Jeong, Myung Ho
    Bueno, Hector
    James, Stefan
    Chiang, Chern-En
    Tresukosol, Damras
    Ongen, Zeki
    Ray, Kausik
    Parkhomenko, Alexander
    McGuire, Darren
    Kosiborod, Mikhail
    Nguyen, Tuan Quang
    Wallentin, Lars
    Fox, Keith A. A.
    Eikelboom, John W.
    Tuomilehto, Jaakko
    Lee, Kerry L.
    Al-Khalidi, Hussein R.
    Ellis, Stephen J.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Holmgren, Pernilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Heldestad, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hallberg, Theresa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Renlund Grausne, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alm, Cristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michelgård Palmquist, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Svanberg, Camilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Capell, Warren H.
    Nehler, Mark R.
    Hiatt, William R.
    Bonaca, Marc P.
    Houser, Stacey
    Bachler, Susie
    Jaeger, Nicole
    Aunes, Maria
    Brusehed, Asa
    Chen, Jersey
    Dahlof, Bjorn
    Dolezalova, Jitka
    Domzol, Maciej
    Findley, Magdalena
    Holmberg, Niclas
    Jahreskog, Marianne
    Knutsson, Mikael
    Kruszewski, Jakub
    Leonsson-Zachrisson, Maria
    Stark, Maj
    Winder, Elin
    Rationale, design and baseline characteristics of the effect of ticagrelor on health outcomes in diabetes mellitus patients Intervention study2019In: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 42, no 5, p. 498-505Article in journal (Refereed)
    Abstract [en]

    In the setting of prior myocardial infarction, the oral antiplatelet ticagrelor added to aspirin reduced the risk of recurrent ischemic events, especially, in those with diabetes mellitus. Patients with stable coronary disease and diabetes are also at elevated risk and might benefit from dual antiplatelet therapy. The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS, NCT01991795) is a Phase 3b randomized, double-blinded, placebo-controlled trial of ticagrelor vs placebo, on top of low dose aspirin. Patients >= 50 years with type 2 diabetes receiving anti-diabetic medications for at least 6 months with stable coronary artery disease as determined by a history of previous percutaneous coronary intervention, bypass grafting, or angiographic stenosis of >= 50% of at least one coronary artery were enrolled. Patients with known prior myocardial infarction (MI) or stroke were excluded. The primary efficacy endpoint is a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety endpoint is Thrombolysis in Myocardial Infarction major bleeding. A total of 19 220 patients worldwide have been randomized and at least 1385 adjudicated primary efficacy endpoint events are expected to be available for analysis, with an expected average follow-up of 40 months (maximum 58 months). Most of the exposure is on a 60 mg twice daily dose, as the dose was lowered from 90 mg twice daily partway into the study. The results may revise the boundaries of efficacy for dual antiplatelet therapy and whether it has a role outside acute coronary syndromes, prior myocardial infarction, or percutaneous coronary intervention.

  • 4.
    Forbes, C. A.
    et al.
    Kleijnen Systemat Reviews Ltd, York, N Yorkshire, England..
    Deshpande, S.
    Kleijnen Systemat Reviews Ltd, York, N Yorkshire, England..
    Sorio-Vilela, F.
    Amgen Europe, Zug, Switzerland.;EEMEA, Zug, Switzerland..
    Kutikova, L.
    Amgen Europe GmbH, Zug, Switzerland..
    Duffy, S.
    Kleijnen Systemat Reviews Ltd, York, N Yorkshire, England..
    Gouni-Berthold, I
    Univ Cologne, Cologne, Germany..
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Comparison Of Methods To Measure Patient Adherence And Persistence With Pharmacological Therapy: A Systematic Review2017In: Value in Health, ISSN 1098-3015, E-ISSN 1524-4733, Vol. 20, no 9, p. A620-A620Article in journal (Other academic)
  • 5.
    Forbes, Carol A.
    et al.
    Kleijnen Systemat Reviews Ltd, York, N Yorkshire, England.
    Deshpande, Sohan
    Kleijnen Systemat Reviews Ltd, York, N Yorkshire, England.
    Sorio-Vilela, Francesc
    Amgen Europe GmbH, Global Hlth Econ, Zug, Switzerland.
    Kutikova, Lucie
    Amgen Europe GmbH, Global Hlth Econ, Zug, Switzerland.
    Duffy, Steven
    Kleijnen Systemat Reviews Ltd, York, N Yorkshire, England.
    Gouni-Berthold, Ioanna
    Univ Cologne, Polyclin Endocrinol Diabet & Prevent Med, Cologne, Germany.
    Hagström, Emil
    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. Uppsala Univ, Dept Med Sci, Uppsala Clin Res Ctr UCR, Uppsala, Sweden.
    A systematic literature review comparing methods for the measurement of patient persistence and adherence2018In: Current Medical Research and Opinion, ISSN 0300-7995, E-ISSN 1473-4877, Vol. 34, no 9, p. 1613-1625Article, review/survey (Refereed)
    Abstract [en]

    Objectives: A systematic literature review was conducted comparing different approaches estimating persistence and adherence in chronic diseases with polypharmacy of oral and subcutaneous treatments. Methods: This work followed published guidance on performing systematic reviews. Twelve electronic databases and grey literature sources were used to identify studies and guidelines for persistence and adherence of oral and subcutaneous therapies in hypercholesterolemia, type 2 diabetes, hypertension, osteoporosis and rheumatoid arthritis. Outcomes of interest of each persistence and adherence data collection and calculation method included pros: accurate, easy to use, inexpensive; and cons: inaccurate, difficult to use, expensive. Results: A total of 4158 records were retrieved up to March 2017. We included 16 observational studies, 5 systematic reviews and 7 guidelines, in patients with hypercholesterolemia (n=8), type 2 diabetes (n=4), hypertension (n=2), rheumatoid arthritis (n=1) and mixed patient populations (n=13). Pharmacy and medical records offer an accurate, easy and inexpensive data collection method. Pill count, medication event monitoring systems (MEMs), self-report questionnaires and observer report are easy to use. MEMS and biochemical monitoring tests can be expensive. Proportion of days covered (PDC) was recommended as a gold standard calculation method for long-term treatments. PDC avoids use of days' supply in calculation, hence is more accurate compared to medication possession ratio (MPR) to assess adherence to treatments in chronic diseases. Conclusions: Decisions on what method to use should be based on considerations of the route of medication administration, the resources available, setting and aim of the assessment. Combining different methods may provide wider insights into adherence and persistence, including patient behavior.

  • 6.
    Guimaraes, Patricia Oliveira
    et al.
    Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA..
    Granger, Christopher B.
    Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA.;Duke Univ, Med Ctr, Durham, NC USA..
    Stebbins, Amanda
    Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA..
    Chiswell, Karen
    Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA..
    Held, Claes
    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.
    Hochman, Judith S.
    NYU, Dept Med, Langone Med Ctr, 550 1St Ave, New York, NY 10016 USA..
    Krug-Gourley, Susan
    GlaxoSmithKline, Metab Pathways & Cardiovasc Therapeut Area, Collegeville, PA USA..
    Lonn, Eva
    McMaster Univ, Dept Med, Hamilton, ON, Canada.;McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Lopes, Renato D.
    Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA.;Duke Univ, Med Ctr, Durham, NC USA..
    Stewart, Ralph A. H.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.;Univ Auckland, Auckland, New Zealand..
    Vinereanu, Dragos
    Univ Med & Pharm Carol Davila, Bucharest, Romania..
    Wallentin, Lars
    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.
    White, Harvey D.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.;Univ Auckland, Auckland, New Zealand..
    Hagström, Emil
    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.
    Danchin, Nicolas
    Hop Europeen Georges Pompidou, AP HP, INSERM U970, Paris, France.;Univ Paris 05, Paris, France..
    Sex Differences in Clinical Characteristics, Psychosocial Factors, and Outcomes Among Patients With Stable Coronary Heart Disease: Insights from the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) Trial2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 9, article id e006695Article in journal (Refereed)
    Abstract [en]

    Background-Greater understanding of differences between men and women with coronary heart disease is needed. Methods and Results-In this post hoc analysis of the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial, we described psychosocial factors, treatments, and outcomes of men versus women with stable coronary heart disease and explored the association of sex with psychosocial characteristics and cardiovascular risk. Cox proportional hazards models were used to assess the relationship between sex and outcomes. Interactions among sex, psychosocial factors, and the composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke were tested. Of 15 828 patients, 2967 (19%) were women. Among women, 21.2% felt often or always stressed at home (versus 9.8% of men), and 19.2% felt often or always sad or depressed (versus 10.1% of men; all P<0.0001). The median duration of follow-up was 3.7 years (25th-75th percentiles: 3.5-3.8 years). Use of evidence-based medications for coronary heart disease at baseline and 24 months was similar between sexes, as were event rates for all outcomes analyzed. In the multivariable model including psychosocial measures, female sex was associated with lower cardiovascular risk. There was a statistically significant interaction (P=0.03) such that the lower risk in women varied by depressive symptom frequency, whereby women who were more depressed had a risk similar to men. Conclusions-Female sex was independently associated with better long-term clinical outcomes, although this was modified by frequency of depressive symptoms. This suggests that emotional state may be an important target for improving outcomes in patients with coronary heart disease, specifically in women.

  • 7.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ahlström, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Ärnlöv, 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.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Parathyroid hormone and calcium are independently associated with subclinical vascular disease in a community-based cohort2015In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 238, no 2, p. 420-426Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    Diseases with abnormal levels of parathyroid hormone (PTH) and calcium, such as primary and secondary hyperparathyroidism, are associated with an increased risk of cardiovascular morbidity and mortality. However, there is paucity on the association between calcium, PTH and abnormalities in the vascular system in the general population.

    METHODS:

    In the PIVUS study (Prospective Investigation of the Vasculature in Uppsala Seniors), a community based cohort of 70-year old men and women (n = 1016), the associations between s-calcium, p-PTH and endothelial function, arterial stiffness and blood pressures were investigated, adjusting for cardiovascular risk factors and mineral metabolism.

    RESULTS:

    In multivariable linear regression models 1 SD increase in calcium was associated with 1.1 units decrease in the stroke volume/pulse pressure ratio and 0.06 decrease in common carotid artery distensibility (p < 0.001) indicative of increased arterial stiffness. Further, calcium was associated with increasing calculated central pulse pressure with 1.3 mmHg elevation per 1 SD increase in calcium (p < 0.05). 1 SD increase in PTH was associated with 1.9 and 1.0 mmHg increase in intra-arterially measured brachial artery systolic and diastolic blood pressures, respectively (p < 0.01), as well as 1.6 and 0.9 mmHg increase in calculated central systolic and diastolic blood pressures (p < 0.05). PTH was not associated with arterial stiffness, endothelial function or pulse pressure.

    CONCLUSION:

    In a large community-based sample of elderly, calcium was independently associated with increased arterial stiffness, and PTH independently to intra-arterial peripheral and calculated central blood pressures. The findings indicate a possible link between the vasculature and mineral metabolism.

  • 8.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Eriksson, Niclas
    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.
    Johansson, Åsa
    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 Immunology, Genetics and Pathology, Genomics.
    Bertilsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Axelsson, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Barratt, Bryan J.
    Becker, Richard C.
    Himmelmann, Anders
    James, Stefan K.
    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.
    Katus, Hugo A.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Steg, Philippe G.
    Storey, Robert F.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Åkerblom, Axel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Are There Any Causal Relations Between Growth Differentiation Factor 15 and Outcomes in Patients With Acute Coronary Syndrome?: - A Report From the Plato Gwas Study2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, no 22Article in journal (Other academic)
  • 9.
    Hagström, Emil
    et al.
    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.
    Held, Claes
    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.
    Response to Letter: 'Sorrow and cardiovascular events'2018In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 283, no 4, p. 415-415Article in journal (Other academic)
  • 10.
    Hagström, Emil
    et al.
    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.
    Held, Claes
    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.
    Stewart, Ralph A H
    Aylward, Philip E
    Budaj, Andrzej
    Cannon, Christopher P
    Koenig, Wolfgang
    Krug-Gourley, Sue
    Mohler, Emile R
    Steg, Philippe Gabriel
    Tarka, Elizabeth
    Östlund, Ollie
    White, Harvey D
    Siegbahn, A
    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.
    Wallentin, Lars
    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.
    Growth Differentiation Factor 15 Predicts All-Cause Morbidity and Mortality in Stable Coronary Heart Disease2017In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 63, no 1, p. 325-333Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Higher growth differentiation factor 15 (GDF-15) concentrations are associated with cardiovascular (CV) and non-CV morbidity and mortality. However, information on associations between GDF-15 and the risk of specific CV and non-CV events in stable coronary heart disease (CHD) patients is limited.

    METHODS: In 14 577 patients with stable CHD participating in the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial (STABILITY), GDF-15 and other prognostic biomarkers (N-terminal pro-B-type natriuretic peptide, high-sensitivity troponin T, cystatin C, and high-sensitivity C-reactive protein) were measured. In adjusted Cox regression models, the associations between GDF-15 and the composite CV end point [CV death, myocardial infarction (MI), and stroke], as well as other CV and non-CV events, were assessed.

    RESULTS: The median concentration (interquartile range) of GDF-15 at baseline was 1253 (915-1827) ng/L. The hazard ratio for the composite end point for the highest compared to the lowest quartile of GDF-15 was 1.8 (95% CI, 1.5-2.2); for CV death, 2.63 (1.9-3.6); for sudden death, 3.06 (1.9-4.8); for heart failure (HF) death, 4.3 (1.3-14); for cancer death, 2.5 (1.3-4.7); for hospitalization for HF, 5.8 (3.2-10); for MI 1.4 (95% CI, 1.1-1.9); and for stroke, 1.8 (95% CI, 1.1-2.8). After adjustment for other prognostic biomarkers, GDF-15 remained significantly associated with all outcomes except for MI.

    CONCLUSIONS: In stable CHD, GDF-15 was independently associated with CV, non-CV, and cancer mortality, as well as with MI and stroke. When also adjusting for other prognostic biomarkers, the associations to all fatal and nonfatal events were maintained except for MI. Information on GDF-15, therefore, might be helpful when assessing the risk of adverse outcomes in patients with stable CHD. ClinicalTrials.gov Identifier: NCT00799903.

  • 11.
    Hagström, Emil
    et al.
    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 Surgical Sciences, Endocrine Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Larsson, Tobias E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Held, Claes
    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.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Plasma parathyroid hormone and the risk of cardiovascular mortality in the community2009In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 119, no 21, p. 2765-2771Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Diseases with elevated levels of parathyroid hormone (PTH) such as primary and secondary hyperparathyroidism are associated with increased incidence of cardiovascular disease and death. However, data on the prospective association between circulating PTH levels and cardiovascular mortality in the community are lacking. METHODS AND RESULTS: The Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based cohort of elderly men (mean age, 71 years; n=958), was used to investigate the association between plasma PTH and cardiovascular mortality. During follow-up (median, 9.7 years), 117 participants died of cardiovascular causes. In Cox proportional-hazards models adjusted for established cardiovascular risk factors (age, systolic blood pressure, diabetes, smoking, body mass index, total cholesterol, high-density lipoprotein cholesterol, antihypertensive treatment, lipid-lowering treatment, and history of cardiovascular disease), higher plasma PTH was associated with higher risk for cardiovascular mortality (hazard ratio for 1-SD increase in PTH, 1.38; 95% confidence interval, 1.18 to 1.60; P<0.001). This association remained essentially unaltered in participants without previous cardiovascular disease and in participants with normal PTH (<6.8 pmol/L) with no other signs of a disturbed mineral metabolism (normal serum calcium, 2.2 to 2.6 mmol/L; normal glomerular filtration rate, >50 mL . min(-1) . 1.73 m(-2) and without vitamin D deficiency, plasma 25-OH vitamin D >37.5 nmol/L). Interestingly, elevated plasma PTH (>5.27 pmol/L) accounted for 20% (95% confidence interval, 10 to 26) of the population-attributable risk proportion for cardiovascular mortality. CONCLUSIONS: Plasma PTH levels predict cardiovascular mortality in the community, even in individuals with PTH within the normal range. Further studies are warranted to evaluate the clinical implications of measuring PTH in cardiovascular risk prediction and to elucidate whether PTH is a modifiable risk factor.

  • 12.
    Hagström, Emil
    et al.
    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 Surgical Sciences, Endocrine Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Lundgren, Ewa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    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 Public Health and Caring Sciences, Geriatrics.
    Serum calcium is independently associated with insulin sensitivity measured with euglycaemic-hyperinsulinaemic clamp in a community-based cohort2007In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 50, no 2, p. 317-324Article in journal (Refereed)
    Abstract [en]

    AIMS/HYPOTHESIS: Diabetes mellitus type 2 is associated with altered calcium metabolism. Moreover, in diseases with supranormal serum calcium levels, such as primary hyperparathyroidism, the prevalence of diabetes is increased. Relatively little is known about the relationship between serum calcium concentration and the underlying causes of diabetes-insulin resistance and defective insulin secretion-in the normocalcaemic general population. MATERIALS AND METHODS: We investigated associations between serum calcium concentration and insulin sensitivity and secretion in a population-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men, n = 961). Insulin sensitivity index (M/I; glucose disposal rate [M] divided by mean insulin concentration [I]) was assessed using euglycaemic-hyperinsulinaemic clamp, and insulin secretion was estimated from the early insulin response (EIR) during an OGTT. RESULTS: In a multivariable linear regression model adjusting for BMI, physical activity, smoking, consumption of tea, alcohol, coffee and dietary calcium, serum phosphate and serum creatinine, 1 SD increase in serum calcium was associated with 0.17 mg kg(-1) min(-1) (mU/l)(-1) x 100 (0.024 mg kg(-1) min(-1) [pmol/l](-1) x 100) decrease in M/I (p = 0.01). The results remained robust in individuals with normal fasting glucose, normal glucose tolerance and serum calcium within the normal range (n = 413, regression coefficient for 1 SD increase -0.45, p = 0.001). Serum calcium was not associated with EIR. Dietary intake of calcium was not independently associated with insulin sensitivity or EIR. CONCLUSION/INTERPRETATION: Our data support the notion that endogenous calcium may be involved early in the development of diabetes and that this effect is mediated mainly through effects on insulin sensitivity rather than defective insulin secretion. Dietary intake of calcium does not seem to influence insulin sensitivity.

  • 13.
    Hagström, Emil
    et al.
    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 Surgical Sciences, Endocrine Surgery.
    Ingelsson, Erik
    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, 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.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Larsson, Tobias E.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Held, Claes
    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.
    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.
    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 Public Health and Caring Sciences, Geriatrics.
    Plasma parathyroid hormone and risk of congestive heart failure in the community2010In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 12, no 11, p. 1186-1192Article in journal (Refereed)
    Abstract [en]

    In experimental studies parathyroid hormone (PTH) has been associated with underlying causes of heart failure (HF) such as atherosclerosis, left ventricular hypertrophy, and myocardial fibrosis. Individuals with increased levels of PTH, such as primary or secondary hyperparathyroidism patients, have increased risk of ischaemic heart disease and HF. Moreover, increasing PTH is associated with worse prognosis in patients with overt HF. However, the association between PTH and the development HF in the community has not been reported. In a prospective, community-based study of 864 elderly men without HF or valvular disease at baseline (mean age 71 years, the ULSAM study) the association between plasma (P)-PTH and HF hospitalization was investigated adjusted for established HF risk factors (myocardial infarction, hypertension, diabetes, electrocardiographic left ventricular hypertrophy, smoking, and hypercholesterolaemia) and variables reflecting mineral metabolism (S-calcium, S-phosphate, P-vitamin D, S-albumin, dietary calcium and vitamin D intake, physical activity, glomerular filtration rate, and blood draw season). During follow-up (median 8 years), 75 individuals were hospitalized due to HF. In multivariable Cox-regression analyses, higher P-PTH was associated with increased HF hospitalization (hazard ratio for 1-SD increase of PTH, 1.41, 95% CI 1.12-1.77, P = 0.003). Parathyroid hormone also predicted hospitalization in participants without apparent ischaemic HF and in participants with normal P-PTH. In a large community-based sample of elderly men, PTH predicted HF hospitalizations, also after accounting for established risk factors and mineral metabolism variables. Our data suggest a role for PTH in the development of HF even in the absence of overt hyperparathyroidism.

  • 14.
    Hagström, Emil
    et al.
    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.
    James, Stefan
    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.
    Bertilsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Becker, Richard C
    Himmelmann, Anders
    Husted, Steen
    Katus, Hugo A
    Steg, Philippe Gabriel
    Storey, Robert F
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Wallentin, Lars
    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.
    Growth differentiation factor-15 level predicts major bleeding and cardiovascular events in patients with acute coronary syndromes: results from the PLATO study2016In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 37, no 16, p. 1325-1333Article in journal (Refereed)
    Abstract [en]

    Aims Growth differentiation factor-15 (GDF-15) predicts death and composite cardiovascular (CV) events in patients with acute coronary syndrome (ACS). We investigated the independent associations between GDF-15 levels and major bleeding, the extent of coronary lesions and individual CV events in patients with ACS. Methods and results Growth differentiation factor-15 was analysed at baseline (n = 16 876) in patients with ACS randomized to ticagrelor or clopidogrel in the PLATO (PLATelet inhibition and patient Outcomes) trial. Growth differentiation factor-15 levels were related to extent of coronary artery disease (CAD) and to all types of non-coronary artery bypass grafting (CABG)-related major bleeding, spontaneous myocardial infarction (MI), stroke, and death during 12-month follow-up. In Cox proportional hazards models adjusting for established risk factors for CV disease and prognostic biomarkers (N-terminal pro B-type natriuretic peptide, cystatin C, high-sensitive C-reactive protein, and high-sensitive troponin T), 1 SD increase in ln GDF-15 was associated with increased risk of major bleeding with a hazard ratio (HR) 1.37 (95% confidence interval: 1.25-1.51) and with a similar increase in risk across different bleeding locations. For the same increase in ln GDF-15, the HR for the composite of CV death, spontaneous MI, and stroke was 1.29 (1.21-1.37), CV death 1.41 (1.30-1.53), all-cause death 1.41 (1.31-1.53), spontaneous MI 1.15 (1.05-1.26), and stroke 1.19 (1.01-1.42). The C-statistic improved for the prediction of CV death and non-CABG-related major bleeding when adding GDF-15 to established risk factors. Conclusions In patients with ACS, higher levels of GDF-15 are associated with raised risks of all types of major non-CABG-related bleeding, spontaneous MI, and stroke as well as CV and total mortality and seem to improve risk stratification for CV-mortality and major bleeding beyond established risk factors.

  • 15.
    Hagström, Emil
    et al.
    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.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Nylander, Ruta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Arnlöv, Johan
    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.
    Plasma Parathyroid Hormone Is Associated with Vascular Dementia and Cerebral Hyperintensities in Two Community-Based Cohorts2014In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 99, no 11, p. 4181-4189Article in journal (Refereed)
    Abstract [en]

    Context:

    In diseases with increased PTH such as hyperparathyroidism and chronic renal failure, dementia is common. Little is known of PTH and dementia in the community.

    Objective:

    We sought to investigate relations between PTH, clinical dementia and cerebral micro-vascular disease.

    Setting and Design:

    The Uppsala Longitudinal Study Of Adult Men (ULSAM) was prospective, baseline, 1991-1995; followup, 15.8 years. The Prospective Investigation Of The Vasculature In Uppsala Seniors (PIVUS) was cross-sectional, baseline, 2001. Both settings were community based.

    Participants and Main Outcome Measure:

    In the ULSAM study of 998 men (age 71) the association between PTH and dementia was investigated. In the PIVUS study of 406 men and women (age 70) the relation between PTH and magnetic resonance imaging signs of cerebral small vascular disease was investigated.

    Results:

    During followup, 56 individuals were diagnosed with vascular, 91 with Alzheimer's, and 59 with other dementias. In Cox-regression analyses, higher PTH was associated with vascular dementia (hazard ratio per 1 SD increase of PTH, 1.41; P < .01), but not with other dementias. The top tertile of PTH accounted for 18.5% of the population-attributable risk for vascular dementia, exceeding all other risk factors. In linear regression analysis in PIVUS, PTH was associated with increasing white matter hyperintensities (WMHI), reflecting increasing burden of cerebral small vessel disease (1 SD PTH increase, 0.31 higher category of WMHI; P = .016). All models were adjusted for vascular risk factors and mineral metabolism.

    Conclusions:

    In two community-based samples, PTH predicted clinically diagnosed and neuroimaging indices of vascular dementia and cerebral small vessel disease. Our data suggest a role for PTH in the development of vascular dementia.

  • 16.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Lundgren, Ewa
    Hellman, Per
    Primary Hyperparathyroidism is associated with low insulin sensitivity and impaired glucose metabolismManuscript (Other academic)
  • 17.
    Hagström, Emil
    et al.
    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 Surgical Sciences, Endocrine Surgery.
    Lundgren, Ewa
    Lithell, Hans
    Berglund, Lars
    Ljunghall, Sverker
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Rastad, Jonas
    Normalized dyslipidaemia after parathyroidectomy in mild primary hyperparathyroidism: population-based study over five years2002In: Clinical Endocrinology (Oxf), ISSN 0300-0664, Vol. 56, no 2, p. 253-260Article in journal (Refereed)
  • 18.
    Hagström, Emil
    et al.
    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 Surgical Sciences, Endocrine Surgery.
    Lundgren, Ewa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Rastad, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Positive effect of parathyroidectomy on bone mineral density in mild asymptomatic primary hyperparathyroidism2006In: Journal of Internal Medicine, ISSN 0954-6820, Vol. 259, no 2, p. 191-198Article in journal (Refereed)
  • 19.
    Hagström, Emil
    et al.
    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 Surgical Sciences, Endocrine Surgery.
    Lundgren, Ewa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Rastad, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Metabolic abnormalities in patients with normocalcemic hyperparathyroidism detected at a population-based screening2006In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 155, no 1, p. 33-39Article in journal (Refereed)
    Abstract [en]

    Objective: Dyslipidemia, hypertension, diabetes mellitus and also primary hyperparathyroidism (pHPT)are associated with an increased risk of cardiovascular diseases. Metabolic abnormalities in mild pHPThave been reported, but never in cases with normal calcium and high parathyroid hormone (PTH)levels, i.e. suffering from ‘normocalcemic pHPT’. Our aim was to explore the occurrence of thesemetabolic abnormalities in individuals with normocalcemic pHPT identified in a population-basedscreening, and the effects of parathyroidectomy vs conservative treatment on metabolic variables.Design and methods: A population-based screening of 5202 post-menopausal women identified 30patients with normal calcium, inappropriately high PTH and normal creatinine. A 5-year follow-upincluded 15 parathyroidectomized (PTx) and nine conservatively followed cases, in a non-randomizedsetting, together with age-matched controls. Biochemical variables and body mass index (BMI) wereinvestigated.Results: At study entry, cases had higher calcium, PTH, glucose, low-density lipoprotein (LDL)/highdensitylipoprotein (HDL)-cholesterol, very low-density lipoprotein (VLDL)-cholesterol, total triglycerides,and BMI compared to controls (PZ!0.0001–0.035). The cases had a lower HDL-cholesterolvalue (PZ0.013) and one third of the cases had hypertriglyceridemia. During follow-up, the PTx casesdecreased in calcium, PTH, LDL/HDL-cholesterol, total and LDL-cholesterol (PZ0.0076–0.022).Investigated biochemical variables remained adverse in conservatively followed cases during follow-upexcept a decreased LDL-cholesterol value. All surgically treated patients had parathyroid adenoma.Conclusions: Cases with normocalcemic pHPT have increased proatherogenic lipoprotein levels, BMIand glucose levels compared to age-matched controls. Parathyroidectomy has positive effects on someof these variables and reverses them to the same level as the controls, while conservative treatmentfails to normalize the investigated metabolic variables.

  • 20.
    Hagström, Emil
    et al.
    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.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Hansen, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular 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.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Arnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Plasma-Parathyroid Hormone Is Associated With Subclinical and Clinical Atherosclerotic Disease in 2 Community-Based Cohorts2014In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 34, no 7, p. 1567-73Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Cardiovascular risk factors have different impact on different arterial territories. Diseases with elevated circulating parathyroid hormone (PTH) such as primary hyperparathyroidism and chronic renal failure have been shown to be associated with an increased risk of cardiovascular disease, predominantly heart or cerebrovascular diseases. However, data on the associations between circulating PTH and peripheral atherosclerosis are limited.

    APPROACH AND RESULTS: Two prospective, community-based studies were used. In 306 men and women, who were 70 years old, from the Prospective investigation of the vasculature in Uppsala seniors (PIVUS) study, cross-sectional relations between PTH and atherosclerotic burden assessed by whole-body magnetic resonance angiography were investigated. In 998 men, who were 71 years old, from the Uppsala longitudinal study of adult men (ULSAM) study, the association between PTH concentration and risk of subsequent nonfatal atherosclerotic disease (excluding coronary or cerebrovascular disease) was investigated. Adjusting for established vascular risk factors, PTH was associated with burden of atherosclerosis (increase in total atherosclerotic score per SD PTH increase: 0.04, 0.003-0.08; P=0.03) in the PIVUS study. During follow-up in the ULSAM study (median 16.7 years), 89 men were diagnosed with nonfatal atherosclerotic disease. In Cox-regression analyses adjusting for established vascular risk factors and mineral metabolism, higher PTH was associated with an increased risk of nonfatal atherosclerotic disease (hazard ratio for 1 SD increase of PTH: 1.55, 1.33-1.88; P<0.0001). Results were similar when including fatal atherosclerotic disease in the outcome.

    CONCLUSIONS: In 2 independent community-based cohorts, PTH was associated to the degree of atherosclerosis and risk of clinically overt atherosclerotic disease, respectively. Our data confirm and extend previous studies supporting a role for PTH in the development of atherosclerotic disease.

  • 21.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Norlund, Fredrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare. Uppsala Univ, Dept Publ Hlth, Uppsala, Sweden.;Uppsala Univ, Caring Sci, Clin Psychol Healthcare, Uppsala, Sweden..
    Harrington, R. A.
    Stanford Univ, Dept Med, Stanford, CA 94305 USA..
    Lopez-Sendon, J.
    Hosp Univ La Paz, Dept Cardiol, IdiPaz, Madrid, Spain..
    Soffer, J.
    GlaxoSmithKline, Metabol Pathways & Cardiovasc Therapeut Area, King Of Prussia, PA USA..
    Stebbins, A.
    Duke Univ, Duke Clin Res Inst, Durham, NC 27706 USA..
    Stewart, R. A. H.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.;Univ Auckland, Auckland 1, New Zealand..
    Wallentin, Lars
    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.
    White, H. D.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.;Univ Auckland, Auckland 1, New Zealand..
    Held, Claes
    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.
    Living alone and depressive symptoms are associated with major cardiovascular events in patients with chronic coronary heart disease2015Conference paper (Refereed)
  • 22.
    Hagström, Emil
    et al.
    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.
    Norlund, Fredrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Psychology in Healthcare.
    Stebbins, Amanda
    Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA..
    Armstrong, P W
    University of Alberta, Edmonton, Canada..
    Chiswell, K
    Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA..
    Granger, C B
    Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA..
    López-Sendón, J
    Hospital Universitario La Paz, Instituto de investigacion IdiPaz, Paseo de la Castellana, Madrid, Spain..
    Pella, D
    Department of Medicine, PJ Safarik University, Kosice, Slovakia..
    Soffer, J
    Metabolic Pathways and Cardiovascular Therapeutic Area, GlaxoSmithKline, Collegeville, PA, USA..
    Sy, R
    Department of Internal Medicine, College of Medicine, University of the Philippines-Manila, Manila, Philippines..
    Wallentin, Lars
    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.
    White, H D
    Green Lane Cardiovascular Service, Auckland, New Zealand.; University of Auckland, Auckland, New Zealand..
    Stewart, R A H
    Green Lane Cardiovascular Service, Auckland, New Zealand.; University of Auckland, Auckland, New Zealand..
    Held, Claes
    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.
    Psychosocial stress and major cardiovascular events in patients with stable coronary heart disease2018In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 283, no 1, p. 83-92Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Assess the risk of ischaemic events associated with psychosocial stress in patients with stable coronary heart disease (CHD).

    METHODS: Psychosocial stress was assessed by a questionnaire in 14 577 patients (median age 65.0, IQR 59, 71; 81.6% males) with stable CHD on optimal secondary preventive therapy in the prospective randomized STABILITY clinical trial. Adjusted Cox regression models were used to assess associations between individual stressors, baseline cardiovascular risk factors and outcomes.

    RESULTS: After 3.7 years of follow-up, depressive symptoms, loss of interest and financial stress were associated with increased risk (hazard ratio, 95% confidence interval) of CV death (1.21, 1.09-1.34; 1.15, 1.05-1.27; and 1.19, 1.08-1.30, respectively) and the primary composite end-point of CV death, nonfatal MI or nonfatal stroke (1.21, 1.13-1.30; 1.19, 1.11-1.27; and 1.17, 1.10-1.24, respectively). Living alone was related to higher risk of CV death (1.68, 1.38-2.05) and the primary composite end-point (1.28, 1.11-1.48), whereas being married as compared with being widowed, was associated with lower risk of CV death (0.64, 0.49-0.82) and the primary composite end-point (0.81, 0.67-0.97).

    CONCLUSIONS: Psychosocial stress, such as depressive symptoms, loss of interest, living alone and financial stress, were associated with increased CV mortality in patients with stable CHD despite optimal medical secondary prevention treatment. Secondary prevention of CHD should therefore focus also on psychosocial issues both in clinical management and in future clinical trials.

  • 23.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Roe, Matthew T.
    Duke Univ, Sch Med, Duke Clin Res Inst, Div Cardiovasc Med, Durham, NC USA..
    Hafley, Gail
    Duke Univ, Sch Med, Duke Clin Res Inst, Dept Stat, Durham, NC USA..
    Neely, Megan L.
    Duke Univ, Sch Med, Duke Clin Res Inst, Dept Stat, Durham, NC USA..
    Sidhu, Mandeep S.
    Albany Stratton VA Med Ctr, Dept Med, Albany, NY USA. Albany Med Coll, Albany Med Ctr, Albany, NY 12208 USA..
    Winters, Kenneth J.
    Eli Lilly & Co, Indianapolis, IN 46285 USA..
    Prabhakaran, Dorairaj
    Ctr Chron Dis Control & Publ Hlth Fdn India, New Delhi, India..
    White, Harvey D.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand..
    Armstrong, Paul W.
    Univ Alberta, Canadian VIGOUR Ctr, Dept Med, Div Cardiol, Edmonton, AB, Canada..
    Fox, Keith A. A.
    Univ Edinburgh, Ctr Cardiovasc Sci, Edinburgh, Midlothian, Scotland..
    Ohman, Magnus
    Duke Univ, Sch Med, Duke Clin Res Inst, Div Cardiovasc Med, Durham, NC USA..
    Boden, William E.
    Albany Stratton VA Med Ctr, Dept Med, Albany, NY USA. Albany Med Coll, Albany Med Ctr, Albany, NY 12208 USA..
    Association Between Very Low Levels of High-Density Lipoprotein Cholesterol and Long-term Outcomes of Patients With Acute Coronary Syndrome Treated Without Revascularization: Insights From the TRILOGY ACS Trial2016In: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 39, no 6, p. 329-337Article in journal (Refereed)
    Abstract [en]

    Background: Low levels of high-density lipoprotein cholesterol (HDL-C; < 40 mg/dL) are associated with increased risk of cardiovascular events, but it is unclear whether lower thresholds (< 30 mg/dL) are associated with increased hazard.

    Hypothesis: Very low levels of HDL-C may provide prognostic information in acute coronary syndrome (ACS) patients treated medically without revascularization.

    Methods: We examined data from 9064/9326 ACS patients enrolled in the TRILOGY ACS trial. Participants were randomized to clopidogrel or prasugrel plus aspirin. Study treatments continued for 6 to 30 months. Relationships between baseline HDL-C and the composite of cardiovascular death, myocardial infarction (MI), or stroke, and individual endpoints of death (cardiovascular and all-cause), MI, and stroke, adjusted for baseline characteristics through 30 months, were analyzed. The HDL-C was evaluated as a dichotomous variable-very low (< 30 mg/dL) vs higher (>= 30 mg/dL)-and continuously.

    Results: Median baseline HDL-C was 42mg/dL (interquartile range, 34-49mg/dL) with little variation over time. Frequency of the composite endpoint was similar for very low vs higher baseline HDL-C, with no risk difference between groups (hazard ratio [ HR]: 1.13, 95% confidence interval [ CI]: 0.95-1.34). Similar findings were seen for MI and stroke. However, risks for cardiovascular (HR: 1.42, 95% CI: 1.13-1.78) and all-cause death (HR: 1.36, 95% CI: 1.11-1.67) were higher in patients with very low baseline HDL-C.

    Conclusions: Medically managed ACS patients with very low baseline HDL-C levels have higher risk of long-term cardiovascular and all-cause death but similar risks for nonfatal ischemic outcomes vs patients with higher baseline HDL-C.

  • 24.
    Hagström, Emil
    et al.
    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.
    Wojdyla, D.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA..
    Neely, M. L.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA..
    Stevens, S. R.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA..
    Harrington, R. A.
    Stanford Univ, Dept Med, Stanford, CA 94305 USA..
    Wallentin, Lars
    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.
    Alexander, J. H.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA..
    Goodman, S. G.
    Univ Toronto, St Michaels Hosp, Canadian Heart Res Ctr, Terrence Donnelly Heart Ctr, Toronto, ON, Canada..
    Lopes, R. D.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA..
    Management and clinical consequences of major bleeding in high-risk patients following an acute coronary syndrome. Is aspirin the problem?: Insights from the APPRAISE-2 trial2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no Suppl. 1, p. 861-862Article in journal (Other academic)
  • 25.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Plasma parathyroid hormone and the risk of cerebrovascular diseases in the community2012In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 33, no Suppl 1, p. 236-236Article in journal (Other academic)
  • 26.
    Hellman, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Low-renin hypertension2014In: Primary aldosteronism: Molocular Genetics, Endocrinology and Translational Medicine / [ed] Hellman, Per, New York: Springer , 2014, p. 39-44Chapter in book (Refereed)
  • 27.
    Hess, Connie N.
    et al.
    Duke Univ, Div Cardiol, Dept Med, Med Ctr, Durham, NC USA.;Duke Clin Res Inst, Durham, NC 27705 USA..
    Roe, Matthew T.
    Duke Univ, Div Cardiol, Dept Med, Med Ctr, Durham, NC USA.;Duke Clin Res Inst, Durham, NC 27705 USA..
    Clare, Robert M.
    Duke Clin Res Inst, Durham, NC 27705 USA..
    Chiswell, Karen
    Duke Clin Res Inst, Durham, NC 27705 USA..
    Kelly, Joseph
    Duke Clin Res Inst, Durham, NC 27705 USA.;Duke Clin Res Inst, Ctr Learning Healthcare, Durham, NC 27705 USA..
    Tcheng, James E.
    Duke Univ, Div Cardiol, Dept Med, Med Ctr, Durham, NC USA.;Duke Clin Res Inst, Durham, NC 27705 USA..
    Hagström, Emil
    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. Uppsala Univ, Dept Med Sci Cardiol, Uppsala, Sweden.;Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden..
    James, Stefan K.
    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.
    Khouri, Michel G.
    Duke Univ, Div Cardiol, Dept Med, Med Ctr, Durham, NC USA..
    Hirsch, Bradford R.
    Duke Clin Res Inst, Durham, NC 27705 USA.;Duke Canc Inst, Durham, NC USA..
    Kong, David F.
    Duke Univ, Div Cardiol, Dept Med, Med Ctr, Durham, NC USA.;Duke Clin Res Inst, Durham, NC 27705 USA..
    Abernethy, Amy P.
    Duke Univ, Div Med Oncol, Dept Med, Med Ctr, Durham, NC USA.;Duke Clin Res Inst, Ctr Learning Healthcare, Durham, NC 27705 USA.;Duke Canc Inst, Durham, NC USA..
    Krucoff, Mitchell W.
    Duke Univ, Div Cardiol, Dept Med, Med Ctr, Durham, NC USA.;Duke Clin Res Inst, Durham, NC 27705 USA..
    Relationship Between Cancer and Cardiovascular Outcomes Following Percutaneous Coronary Intervention2015In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, no 7, article id e001779Article in journal (Refereed)
    Abstract [en]

    Background-Cardiovascular disease and cancer increasingly coexist, yet relationships between cancer and long-term cardiovascular outcomes post-percutaneous coronary intervention (PCI) are not well studied. Methods and Results-We examined stented PCI patients at Duke (1996-2010) using linked data from the Duke Information Systems for Cardiovascular Care and the Duke Tumor Registry (a cancer treatment registry). Our primary outcome was cardiovascular mortality. Secondary outcomes included composite cardiovascular mortality, myocardial infarction, or repeat revascularization and all-cause mortality. We used adjusted cause-specific hazard models to examine outcomes among cancer patients (cancer treatment pre-PCI) versus controls (no cancer treatment pre-PCI). Cardiovascular mortality was explored in a cancer subgroup with recent (within 1 year pre-PCI) cancer and in post-PCI cancer patients using post-PCI cancer as a time-dependent variable. Among 15 008 patients, 3.3% (n=496) were cancer patients. Observed rates of 14-year cardiovascular mortality (31.4% versus 27.7%, P=0.31) and composite cardiovascular death, myocardial infarction, or revascularization (51.1% versus 55.8%, P=0.37) were similar for cancer versus control groups; all-cause mortality rates were higher (79.7% versus 49.3%, P<0.01). Adjusted risk of cardiovascular mortality was similar for cancer patients versus controls (hazard ratio 0.95; 95% CI 0.76 to 1.20) and for patients with versus without recent cancer (hazard ratio 1.46; 95% CI 0.92 to 2.33). Post-PCI cancer, present in 4.3% (n=647) of patients, was associated with cardiovascular mortality (adjusted hazard ratio 1.51; 95% CI 1.11 to 2.03). Conclusions-Cancer history was present in a minority of PCI patients but was not associated with worse long-term cardiovascular outcomes. Further investigation into PCI outcomes in this population is warranted.

  • 28.
    Johansson, Åsa
    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, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Eriksson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Becker, Richard C.
    Storey, Robert F.
    Himmelmann, Anders
    Hagström, Emil
    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.
    Varenhorst, Christoph
    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.
    Axelsson, Tomas
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Barratt, Bryan J.
    James, Stefan K.
    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.
    Katus, Hugo A.
    Steg, Philippe Gabriel
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Wallentin, Lars
    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.
    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.
    NLRC4 Inflammasome Is an Important Regulator of Interleukin-18 Levels in Patients With Acute Coronary Syndromes Genome-Wide Association Study in the PLATelet inhibition and patient Outcomes Trial (PLATO)2015In: Circulation: Cardiovascular Genetics, ISSN 1942-325X, E-ISSN 1942-3268, Vol. 8, no 3, p. 498-506Article in journal (Refereed)
    Abstract [en]

    Background Interleukin 18 (IL-18) promotes atherosclerotic plaque formation and is increased in patients with acute coronary syndromes. However the relative contribution of genetic variants to the IL-18 levels has not been fully determined. Methods and Results Baseline plasma IL-18 levels were measured in 16633 patients with acute coronary syndrome, of whom 9340 had genetic data that passed genotype quality control. A 2-stage genome-wide association study was performed, followed by combined analyses using >10 million genotyped or imputed genetic markers. Single nucleotide polymorphisms at 3 loci (IL18, NLRC4, and MROH6) were identified (P<3.15x10(-8)) in the discovery cohort (n=3777) and replicated in the remaining patients (n=5563). In the pooled data (discovery+replication cohort), 7 independent associations, in 5 chromosomal regions, were associated with IL-18 levels (minimum P=6.99x10(-72)). Six single nucleotide polymorphisms are located in predicted promoter regions of which one disrupts a transcription factor binding site. One single nucleotide polymorphism in NLRC4 is a rare missense variant, predicted to be deleterious to the protein. Altogether, the identified genetic variants explained 8% of the total variation in IL-18 levels in the cohort. Conclusions Our results show that genetic variants play an important role in determining IL-18 levels in patients with acute coronary syndrome and we have identified genetic variants located in the IL-18 gene (IL18) or close to genes that are involved in procaspase-1 activation (NLRC4 and CARD16, CARD17, and CARD18). These associations also highlight the importance of the NLRC4 inflammasome for IL-18 production in acute coronary syndrome patients.

  • 29.
    Journath, Gunilla
    et al.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Cardiol Unit, Stockholm, Sweden..
    Hambraeus, Kristina
    Falun Cent Hosp, Dept Cardiol, Falun, Sweden..
    Hagström, Emil
    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.
    Pettersson, Billie
    Amgen Inc, Thousand Oaks, CA 91320 USA..
    Lothgren, Mickael
    Amgen Europe GmbH, Zug, Switzerland..
    Predicted impact of lipid lowering therapy on cardiovascular and economic outcomes of Swedish atherosclerotic cardiovascular disease guideline2017In: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 17, article id 224Article in journal (Refereed)
    Abstract [en]

    Background: The effects on cardiovascular disease (CVD) by treatment recommendations on prevention of atherosclerotic CVD remain to be evaluated. The objectives were to assess treatment gap for low density lipoprotein cholesterol (LDL-C) according to guidelines, potential impact on CVD outcomes, and possible avoided economic costs, in post myocardial infarction (MI) patients, if target LDL-C levels of <= 1.8 mmol/L would be achieved. Methods: All patients registered in the Swedish Secondary Prevention after Heart Intensive care Admission register, with one-year post-MI follow-up during 2013 were selected. The REACH risk prediction and a calibrated model for recurrent cardiovascular events and death were used to estimate unadjusted risk prediction based on the REACH equation henceforth called base case, and calibrated CVD outcomes based on gender-specific risk factors. The predicted impact of the LDL-C reduction on the risk of CVD was based on the Cholesterol Treatment Trialists' Collaboration findings. Results: A sample of n = 5904 patients (74% men) with a mean age of 64 years were included. Around 70% did not reach LDL-C target = 1.8 mmol/L. Over a 10-year period, 820-2262 events were predicted to occur in those who did not reach target corresponding to 20%-55% risk of CVD events. To achieve LDL-C target, the mean LDL-C had to be reduced by 0.73 mmol/L (29%). If this LDL-C reduction was achieved, 195-544 life years, 132-343 CVD events, and 7.9-20.9 million Swedish crowns (MSEK) of direct costs, and 19.3-51.0 MSEK of total costs would be avoided. Conclusion: Lowering of LDL cholesterol to achieve target levels according to guidelines for post-MI patients may lead to fewer cardiovascular events and avoidance of event costs.

  • 30.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Hagström, Emil
    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.
    Nilsson, Lennart
    Department of Medical and Health Sciences , Linkoping University , Linkoping , Sweden..
    Svensson, Maria K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Treatment target re-classification of subjects comparing estimation of low-density lipoprotein cholesterol by the Friedewald equation and direct measurement of LDL-cholesterol2018In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 2, p. 94-99Article in journal (Refereed)
    Abstract [en]

    AIMS: To compare low-density lipoprotein cholesterol (LDL-C) values calculated by the Friedewald equation with direct LDL-C in patient samples and assess the possible impact on re-classification of LDL-C target values for primary prevention or high cardiovascular disease (CVD) risk (<2.5 mmol/L) and secondary prevention or very high CVD risk (<1.8 mmol/L). LDL-C is an important CVD risk factor. Over the last decade, there has been a change in laboratory methodology from indirectly calculated LDL-C with the Friedewald equation to direct LDL-C measurements (dLDL-C).

    METHODS: Reported results for plasma triglycerides, total cholesterol, high-density lipoprotein-cholesterol, and dLDL-C from 34,981 samples analyzed in year 2014 were extracted from the laboratory information system, Uppsala University Hospital, Uppsala, Sweden.

    RESULTS: dLDL-C was approximately 10% lower than the corresponding LDL-C results calculated by the Friedewald equation in both men and women. In subjects with triglyceride concentrations above 4 mmol/L (n = 1250) the same discordant pattern was seen as for the entire study population. Altogether 5469 out of 18,051 men (30.3%) and 4604 out of 16,928 women (27.2%) were down-classified at least one CVD risk category. A very small number of subject was up-classified, in total 37 out of 18,051 men (0.2%) and 28 out of 16,928 women (0.2%).

    CONCLUSIONS: The two LDL-C methods had a high concordance, but the direct LDL-C measurement consistently gave approx. 10% lower values, and this caused one-third of subjects to be re-classified as having a lower cardiovascular disease risk in relation to recommended LDL-C target values and decision limits.

  • 31. Larsson, Tobias E
    et al.
    Olauson, Hannes
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ärnlöv, Johan
    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.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Conjoint effects of serum calcium and phosphate on risk of total, cardiovascular, and noncardiovascular mortality in the community2010In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 30, no 2, p. 333-339Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Hyperphosphatemia is a cardiovascular risk factor in patients with chronic kidney disease. Relations of circulating calcium (Ca) and phosphorus (Pi) to long-term mortality risk in the community require further investigation. METHODS AND RESULTS: Associations of serum Ca and Pi to mortality were evaluated in a community-based cohort of 2176 men (mean age, 50.1 years). During follow-up (median, 29.8 years), 1009 men died, and 466 of these deaths resulted from cardiovascular causes. In Cox proportional hazards models, serum Pi and [CaxPi] were independent predictors of total mortality (hazard ratio per SD, 1.06; 95% CI, 1.01-1.12; P=0.03; 1.07; 95% CI, 1.01-1.12; P=0.01) and cardiovascular mortality (1.10; 95% CI, 1.02-1.18; P=0.01; 1.10; 95% CI, 1.03-1.19; P=0.008). Serum Ca was associated with risk of total mortality (1.08; 95% CI, 1.01-1.16; P=0.02) and noncardiovascular mortality (1.10; 95% CI, 1.01-1.21; P=0.04). Results were consistent after multivariate adjustments in subsamples of individuals with estimated glomerular filtration rate >90 mL/min and low-to-normal serum Ca and Pi. CONCLUSIONS: Circulating Ca and Pi levels are associated with risks of total, cardiovascular, and noncardiovascular mortality in the community, and their conjoint effects are additive. Additional studies are warranted to evaluate whether Ca and Pi are modifiable risk factors in the general population.

  • 32. Levin, G. P.
    et al.
    Robinson-Cohen, C.
    De Boer, I. H.
    Houston, D. K.
    Lohman, K.
    Liu, Y.
    Kritchevsky, S. B.
    Cauley, J. A.
    Tanaka, T.
    Ferrucci, L.
    Bandinelli, S.
    Patel, K. V.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Wang, T.
    Wolf, M.
    Psaty, B. M.
    Siscovick, D.
    Kestenbaum, B.
    Genetic variants and associations of 25-hydroxyvitamin D concentrations with major clinical outcomes2012In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 308, no 18, p. 1898-1905Article in journal (Refereed)
    Abstract [en]

    Context Lower serum 25-hydroxyvitamin D concentrations are associated with greater risks of many chronic diseases across large, prospective community-based studies. Substrate 25-hydroxyvitamin D must be converted to 1,25-dihydroxyvitamin D for full biological activity, and complex metabolic pathways suggest that interindividual variability in vitamin D metabolism may alter the clinical consequences of measured serum 25-hydroxyvitamin D.

    Objective To investigate whether common variation within genes encoding the vitamin D–binding protein, megalin, cubilin, CYP27B1, CYP24A1, and the vitamin D receptor (VDR) modify associations of low 25-hydroxyvitamin D with major clinical outcomes.

    Design, Setting, and Participants Examination of 141 single-nucleotide polymorphisms in a discovery cohort of 1514 white participants (who were recruited from 4 US regions) from the community-based Cardiovascular Health Study. Participants had serum 25-hydroxyvitamin D measurements in 1992-1993 and were followed up for a median of 11 years (through 2006). Replication meta-analyses were conducted across the independent, community-based US Health, Aging, and Body Composition (n = 922; follow-up: 1998-1999 through 2005), Italian Invecchiare in Chianti (n = 835; follow-up: 1998-2000 through 2006), and Swedish Uppsala Longitudinal Study of Adult Men (n = 970; follow-up: 1991-1995 through 2008) cohort studies.

    Main Outcome Measure Composite outcome of incident hip facture, myocardial infarction, cancer, and mortality over long-term follow-up.

    Results Interactions between 5 single-nucleotide polymorphisms and low 25-hydroxyvitamin D concentration were identified in the discovery phase and 1 involving a variant in the VDR gene replicated in independent meta-analysis. Among Cardiovascular Health Study participants, low 25-hydroxyvitamin D concentration was associated with hazard ratios for risk of the composite outcome of 1.40 (95% CI, 1.12-1.74) for those who had 1 minor allele at rs7968585 and 1.82 (95% CI, 1.31-2.54) for those with 2 minor alleles at rs7968585. In contrast, there was no evidence of an association (estimated hazard ratio, 0.93 [95% CI, 0.70-1.24]) among participants who had 0 minor alleles at this single-nucleotide polymorphism.

    Conclusion Known associations of low 25-hydroxyvitamin D with major health outcomes may vary according to common genetic differences in the vitamin D receptor.

  • 33.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sundström, Johan
    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.
    Hagström, Emil
    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, Dept Hlth & Social Sci, Falun, Sweden..
    Discovery of new biomarkers for atrial fibrillation using a custom-made proteomics chip2017In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 103, no 5, p. 379-384Article in journal (Refereed)
    Abstract [en]

    Background Apart from several established clinical risk factors for atrial fibrillation (AF), a number of biomarkers have also been identified as potential risk factors for AF. None of these have so far been adopted in clinical practice. Objective To use a novel custom-made proteomics chip to discover new prognostic biomarkers for AF risk. Methods In two independent community-based cohorts (Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (978 participants without AF, mean age 70.1 years, 50% women, median followup 10.0 years) and Uppsala Longitudinal Study of Adult Men (ULSAM) (n= 725, mean age 77.5 years, median follow-up 7.9 years)), ninety-two plasma proteins were assessed at baseline by a proximity extension assay (PEA) chip. Of those, 85 proteins showed a call rate > 70% in both cohorts. Results Thirteen proteins were related to incident AF in PIVUS (148 events) using a false discovery rate of 5%. Of those, five were replicated in ULSAM at nominal multivariable p value (123 events, N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), fibroblast growth factor 23 (FGF-23), fatty acid-binding protein 4 (FABP4), growth differentiation factor 15 (GDF-15) and interleukin-6 (IL-6)). Of those, NT-pro-BNP and FGF-23 were also associated with AF after adjusting for established AF risk factors. In a prespecified secondary analysis pooling the two data sets, T-cell immunoglobulin and mucin domain 1 (TIM-1) and adrenomedullin (AM) were also significantly related to incident AF in addition to the aforementioned five proteins (Bonferroni-adjustment). The addition of NT-proBNP to a model with established risk factors increased the C-statistic from 0.605 to 0.676 (p< 0.0001). Conclusions Using a novel proteomics approach, we confirmed the previously reported association between NT-pro-BNP, FGF-23, GDF-15 and incident AF, and also discovered four proteins (FABP4, IL-6, TIM-1 and AM) that could be of importance in the development of AF.

  • 34.
    Lindholm, Daniel
    et al.
    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.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Armstrong, Paul W.
    Budaj, Andrzej
    Cannon, Christopher P.
    Granger, Christopher B.
    Hagström, Emil
    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.
    Held, Claes
    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.
    Koenig, Wolfgang
    Östlund, Ollie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Stewart, Ralph A.H.
    Soffer, Joseph
    White, Harvey D.
    de Winter, Robbert J.
    Steg, Philippe Gabriel
    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, Clinical Chemistry.
    Kleber, Marcus E.
    Dressel, Alexander
    Grammer, Tanja B.
    März, Winfried
    Wallentin, Lars
    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.
    Biomarker-Based Risk Model to Predict Cardiovascular Mortality in Patients With Stable Coronary Disease2017In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 70, no 7, p. 813-826Article in journal (Refereed)
    Abstract [en]

    Background Currently, there is no generally accepted model to predict outcomes in stable coronary heart disease (CHD).Objectives This study evaluated and compared the prognostic value of biomarkers and clinical variables to develop a biomarker-based prediction model in patients with stable CHD.Methods In a prospective, randomized trial cohort of 13,164 patients with stable CHD, we analyzed several candidate biomarkers and clinical variables and used multivariable Cox regression to develop a clinical prediction model based on the most important markers. The primary outcome was cardiovascular (CV) death, but model performance was also explored for other key outcomes. It was internally bootstrap validated, and externally validated in 1,547 patients in another study.Results During a median follow-up of 3.7 years, there were 591 cases of CV death. The 3 most important biomarkers were N-terminal pro–B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and low-density lipoprotein cholesterol, where NT-proBNP and hs-cTnT had greater prognostic value than any other biomarker or clinical variable. The final prediction model included age (A), biomarkers (B) (NT-proBNP, hs-cTnT, and low-density lipoprotein cholesterol), and clinical variables (C) (smoking, diabetes mellitus, and peripheral arterial disease). This “ABC-CHD” model had high discriminatory ability for CV death (c-index 0.81 in derivation cohort, 0.78 in validation cohort), with adequate calibration in both cohorts.Conclusions This model provided a robust tool for the prediction of CV death in patients with stable CHD. As it is based on a small number of readily available biomarkers and clinical factors, it can be widely employed to complement clinical assessment and guide management based on CV risk. (The Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial [STABILITY]; NCT00799903)

  • 35.
    Lindholm, Daniel P
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Becker, Richard C
    Cannon, Christopher P
    Himmelmann, Anders
    Katus, Hugo A
    Maurer, Gerald
    López-Sendón, José Luis
    Steg, Philippe Gabriel
    Storey, Robert F
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Growth Differentiation Factor 15 at 1 Month After an Acute Coronary Syndrome Is Associated With Increased Risk of Major Bleeding.2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 4, article id e005580Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Growth differentiation factor-15 (GDF-15) is related to major bleeding when measured at initial presentation in patients with acute coronary syndromes (ACSs) treated with dual antiplatelet therapy. It is unknown whether follow-up measurements provide additional information. The objective of this study was to investigate whether GDF-15 measured 1 month after an ACS provides additional information beyond the baseline levels with regard to the risk of major bleeding.

    METHODS AND RESULTS: GDF-15 was measured at baseline and at 1 month after an ACS in 4049 patients included in the PLATelet inhibition and patient Outcomes (PLATO) trial. The association between 1-month GDF-15 level and non-coronary artery bypass grafting surgery-related major bleeding was assessed by a multivariable Cox model, adjusting for baseline GDF-15, age, anemia, impaired renal function, history of gastrointestinal bleeding, and sex. Elevated GDF-15 (>1800 ng/L) at 1 month was associated with an increased risk of non-coronary artery bypass grafting-related major bleeding (3.9% versus 1.2%; hazard ratio, 3.38; 95% CI, 1.89-6.06), independent of baseline GDF-15. Patients who had elevated GDF-15 levels at baseline and subsequent nonelevated GDF-15 at 1 month had a similar risk as patients who had nonelevated levels at both measurements.

    CONCLUSIONS: GDF-15 at 1 month after an ACS is related to the risk of bleeding during DAPT and provides additional information on the bleeding risk beyond baseline GDF-15 levels. GDF-15 levels may therefore be useful as part of decision support concerning long-term antithrombotic treatment in patients post-ACS.

    CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.

  • 36.
    Oskarsson, A.
    et al.
    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.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Wernroth, Mona-Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Becker, R. C.
    Held, Claes
    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.
    Himmelmann, A.
    Storey, R. F.
    Wallentin, Lars
    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.
    James, Stefan
    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.
    ApoA1 is independently associated with recurrent ischemic events and death in acute coronary syndrome patients2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, p. 482-482Article in journal (Refereed)
  • 37.
    Patel, Riyaz S.
    et al.
    UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England;St Bartholomews Hosp, Barts Heart Ctr, London, England.
    Schmidt, Amand F.
    UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England;UMC, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands.
    Tragante, Vinicius
    UMC, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands.
    McCubrey, Raymond O.
    Intertermt Med Ctr, Intermt Heart Inst, Salt Lake City, UT USA.
    Holmes, Michael, V
    Univ Oxford, Clin Trial Serv Unit, Nuffield Dept Populat Hlth, Oxford, England;Univ Oxford, Epidemiol Studies Unit, Nuffield Dept Populat Hlth, Oxford, England;Univ Oxford, Med Res Council Populat Hlth Res Unit, Oxford, England;Univ Oxford, Natl Inst Hlth Res, Oxford Biomed Res Ctr, Oxford, England.
    Howe, Laurence J.
    UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England.
    Direk, Kenan
    UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England.
    Åkerblom, Axel
    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.
    Leander, Karin
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Virani, Salim S.
    Baylor Coll Med, Sect Cardiovasc Res, Michael & DeBakey Vet Affairs Med Ctr, Sect Cardiol, Houston, TX 77030 USA;Baylor Coll Med, Dept Med, Sect Cardiol, Houston, TX 77030 USA.
    Kaminski, Karol A.
    Med Univ Bialystok, Dept Populat Med & Civilizat Dis Prevent, Bialystok, Poland;Med Univ Bialystok, Dept Cardiol, Bialystok, Poland.
    Muehlschlegel, Jochen D.
    UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England;St Bartholomews Hosp, Barts Heart Ctr, London, England;Harvard Med Sch, 75 Francis St, Boston, MA 02115 USA.
    Dube, Marie-Pierre
    Univ Montreal, Fac Med, Montreal, PQ, Canada.
    Allayee, Hooman
    USC, Dept Prevent Med, Los Angeles, CA USA;USC, Dept Biochem & Mol Med, Los Angeles, CA USA.
    Almgren, Peter
    Lund Univ, Dept Clin Sci, Malmo, Sweden.
    Alver, Maris
    Univ Tartu, Inst Mol & Cell Biol, Dept Biotechnol, Tartu, Estonia.
    Baranova, Ekaterina, V
    Univ Med Ctr, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands.
    Behlouli, Hassan
    McGill Univ Hlth Ctr, Res Inst, Montreal, PQ, Canada;German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
    Boeckx, Bram
    Katholieke Univ Leuven, Dept Human Genet, Lab Translat Genet, Leuven, Belgium;VIB, VIB Ctr Canc Biol, Lab Translat Genet, Ghent, Belgium.
    Braund, Peter S.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England;Univ Leicester, Dept Hlth Sci, Leicester, Leics, England;Glenfield Hosp, NIHR, Leicester, Leics, England.
    Breitling, Lutz P.
    McGill Univ Hlth Ctr, Res Inst, Montreal, PQ, Canada;German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
    Delgado, Graciela
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Mannheim, Germany.
    Duarte, Nubia E.
    Univ Sao Paulo, Heart Inst, Sao Paulo, Brazil.
    Dufresne, Line
    McGill Univ Hlth Ctr, Res Inst, Montreal, PQ, Canada;McGill Univ Hlth Ctr, Prevent & Genom Cardiol, Montreal, PQ, Canada.
    Eriksson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Foco, Luisa
    Univ Lubeck, Affiliated Inst, Eurac Res, Inst Biomed, Bolzano, Italy.
    Gijsberts, Crystel M.
    UMC, Lab Expt Cardiol, Utrecht, Netherlands.
    Gong, Yan
    Univ Florida, Dept Pharmacotherapy & Translat Res, Gainesville, FL USA;Univ Florida, Ctr Pharmacogen, Gainesville, FL USA.
    Hartiala, Jaana
    USC, Dept Prevent Med, Los Angeles, CA USA;USC, Dept Biochem & Mol Med, Los Angeles, CA USA;USC, Keck Sch Med, Inst Genet Med, Los Angeles, CA USA.
    Heydarpour, Mahyar
    Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, 75 Francis St, Boston, MA 02115 USA.
    Hubacek, Jaroslav A.
    Inst Clin & Expt Med, Ctr Expt Med, Prague, Czech Republic.
    Kleber, Marcus
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Mannheim, Germany.
    Kofink, Daniel
    UMC, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands.
    Kuukasjarvi, Pekka
    Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Ctr, Dept Cardiothorac Surg, Tampere, Finland.
    Lee, Vei-Vei
    Texas Heart Inst, Dept Biostat & Epidemiol, Houston, TX 77025 USA.
    Leiherer, Andreas
    VIVIT, Feldkirch, Austria;Private Univ Principal Liechtenstein, Triesen, Liechtenstein;Med Cent Labs, Feldkirch, Austria.
    Lenzini, Petra A.
    Washington Univ, Sch Med, Dept Genet, Stat Genom Div, St Louis, MO 63110 USA;Univ Sao Paulo, Hosp Univ, Ctr Pesquisa Clin, Sao Paulo, Brazil.
    Levin, Daniel
    Univ Dundee, Sch Med, Div Mol & Clin Med, Dundee, Scotland.
    Lyytikainen, Leo-Pekka
    Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Ctr, Dept Clin Chem, Tampere, Finland;Fimlab Labs, Dept Clin Chem, Tampere, Finland.
    Martinelli, Nicola
    Univ Verona, Dept Med, Verona, Italy.
    Mons, Ute
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
    Nelson, Christopher P.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England;Univ Leicester, Dept Hlth Sci, Leicester, Leics, England;Glenfield Hosp, NIHR, Leicester, Leics, England.
    Nikus, Kjell
    Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Ctr, Dept Cardiol, Tampere, Finland;Tampere Univ Hosp, Dept Cardiol, Heart Ctr, Tampere, Finland.
    Pilbrow, Anna P.
    Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Sch Med, Atlanta, GA 30322 USA.
    Ploski, Rafal
    Med Univ Warsaw, Dept Med Genet, Warsaw, Poland.
    Sun, Yan, V
    Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Sch Med, Atlanta, GA 30322 USA;Emory Univ, Sch Med, Dept Biomed Informat, Atlanta, GA 30322 USA.
    Tanck, Michael W. T.
    Univ Utrecht, Dept Internal Med, Sect Gerontol & Geriatr, Utrecht, Netherlands.
    Tang, W. H. Wilson
    Cleveland Clin, Lerner Res Inst, Dept Cellular & Mol Med, Cleveland, OH 44106 USA;Cleveland Clin, Dept Cardiovasc Med, Heart & Vasc Inst & Ctr Microbiome & Human Hlth, Cleveland, OH 44106 USA.
    Trompet, Stella
    Univ Utrecht, Dept Internal Med, Sect Gerontol & Geriatr, Utrecht, Netherlands;Univ Utrecht, Dept Cardiol, Utrecht, Netherlands.
    van der Laan, Sander W.
    Univ Med Ctr, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands;Univ Utrecht, Div Labs Pharm & Biomed Genet, Leiden Univ Med Ctr, Lab Clin Chem & Hematol, Utrecht, Netherlands.
    van Setten, Jessica
    ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.
    Vilmundarson, Ragnar O.
    Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada;Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON, Canada.
    Anselmi, Chiara Viviani
    Humanitas Clin & Res Ctr, Dept Cardiovasc Med, Milan, Italy.
    Vlachopoulou, Efthymia
    Univ Helsinki, Transplantat Lab, Med, Helsinki, Finland.
    Boerwinkle, Eric
    Univ Texas Houston, Sch Publ Hlth, Houston, TX USA.
    Briguori, Carlo
    Clin Mediterranea, Naples, Italy.
    Carlquist, John F.
    Intertermt Med Ctr, Intermt Heart Inst, Salt Lake City, UT USA;Univ Utah, Dept Internal Med, Cardiol Div, Salt Lake City, UT 84112 USA.
    Carruthers, Kathryn F.
    Univ Edinburgh, Cardiovasc Sci, Edinburgh, Midlothian, Scotland.
    Casu, Gavino
    ATS Sardegna, ASL 3, Nuoro, Italy.
    Deanfield, John
    INESSS, Unite Evaluat Cardiovasc, Montreal, PQ, Canada.
    Deloukas, Panos
    Barts & London Med Sch, William Harvey Res Inst, London, England;Queen Mary Univ London, Ctr Genom Hlth, London, England.
    Dudbridge, Frank
    BHF Cardiovasc Res Ctr, Leicester, Leics, England.
    Fitzpatrick, Natalie
    UCL, Inst Hlth Informat, Fac Populat Hlth Sci, London, England.
    Gigante, Bruna
    UMC, Dept Clin Chem & Hematol, Utrecht, Netherlands.
    James, Stefan
    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.
    Lokki, Marja-Liisa
    Univ Helsinki, Transplantat Lab, Med, Helsinki, Finland.
    Lotufo, Paulo A.
    Jagiellonian Univ, Med Coll, Dept Internal Med, Krakow, Poland.
    Marziliano, Nicola
    ATS Sardegna, ASL 3, Nuoro, Italy.
    Mordi, Ify R.
    Univ Dundee, Sch Med, Div Mol & Clin Med, Dundee, Scotland.
    Muhlestein, Joseph B.
    Univ Utah, Dept Internal Med, Cardiol Div, Salt Lake City, UT 84112 USA.
    Cheh, Chris Newton
    Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston & Program Med & Populat Genet, Brd Inst, Cambridge, MA USA;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston & Program Med & Populat Genet, Brd Inst, Cambridge, MA USA.
    Pitha, Jan
    Inst Clin & Expt Med, Ctr Expt Med, Prague, Czech Republic.
    Saely, Christoph H.
    UCL, Inst Hlth Informat, Fac Populat Hlth Sci, London, England;VIVIT, Feldkirch, Austria;Private Univ Principal Liechtenstein, Triesen, Liechtenstein.
    Samman-Tahhan, Ayman
    Emory Univ, Sch Med, Dept Med, Emory Clin Cardiovasc Res Inst, Atlanta, GA USA.
    Sandesara, Pratik B.
    Emory Univ, Sch Med, Dept Med, Emory Clin Cardiovasc Res Inst, Atlanta, GA USA.
    Teren, Andrej
    Heart Ctr Leipzig, Acad Teaching Hosp Feldkirch, Dept Med & Cardiol, Leipzig, Germany;Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany.
    Timmis, Adam
    UCL, Inst Hlth Informat, Fac Populat Hlth Sci, London, England;St Bartholomews Hosp, Barts Heart Ctr, London, England.
    Van de Werf, Frans
    Katholieke Univ Leuven, Dept Cardiovasc Sci, Leuven, Belgium.
    Wauters, Els
    Katholieke Univ Leuven, Univ Hosp, Dept Resp Med, Resp Oncol Unit, Leuven, Belgium.
    Wilde, Arthur A. M.
    Princess Jawhara Brah Ctr Excellence Res Heredita, Jeddah, Saudi Arabia.
    Ford, Ian
    Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
    Stott, David J.
    Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
    Algra, Ale
    Univ Med Ctr, Dept Neurol & Neurosurg, Brain Ctr Rudolf Magnus, Utrecht, Netherlands;Univ Med Ctr, Dept Neurol & Neurosurg, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
    Andreassi, Maria G.
    CNR, Inst Clin Physiol, Pisa, Italy.
    Ardissino, Diego
    Parma Univ Hosp, Cardiol Dept, Parma, OH USA.
    Arsenault, Benoit J.
    Inst Univ cardiol & Pneumol Quebec, Ctr Rech, Quebec City, PQ, Canada;Univ Laval, Fac Med, Dept Med, Laval, PQ, Canada.
    Ballantyne, Christie M.
    Baylor Coll Med, Sect Cardiovasc Res, Michael & DeBakey Vet Affairs Med Ctr, Sect Cardiol, Houston, TX 77030 USA;Baylor Coll Med, Dept Med, Sect Cardiol, Houston, TX 77030 USA.
    Bergmeijer, Thomas O.
    St Antonius Hosp, Dept Cardiol, Nieuwegein, Netherlands.
    Bezzina, Connie R.
    Univ Amsterdam, Clin Epidemiol & Biostat, AMC Heart Ctr, Amsterdam, Netherlands.
    Body, Simon C.
    Harvard Med Sch, 75 Francis St, Boston, MA 02115 USA;Beth Israel Deaconess Med Ctr, Dept Anesthesia Pain & Crit Care, Boston, MA 02215 USA.
    Bogaty, Peter
    Inst Univ Cardiol & Pneumol Quebec, Dept Multidisciplinaire Cardiol, Serv Cardiol, Quebec City, PQ, Canada;INESSS, Unite Evaluat Cardiovasc, Montreal, PQ, Canada;Laval Univ, Inst Univ Cardiol & Pnemol Quebec, Quebec City, PQ, Canada.
    de Borst, Gert J.
    Univ Utrecht, Univ Med Ctr Utrecht, Dept Vasc Surg, Utrecht, Netherlands.
    Brenner, Hermann
    ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.
    Burkhardt, Ralph
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Univ Hosp Regensburg, Inst Clin Chem & Lab Med, Regensburg, Germany.
    Carpeggiani, Clara
    CNR, Inst Clin Physiol, Pisa, Italy.
    Condorelli, Gianluigi
    Humanitas Clin & Res Ctr, Dept Cardiovasc Med, Milan, Italy;Humanitas Univ, Dept Biomed Sci, Milan, Italy.
    Cooper-DeHoff, Rhonda M.
    Univ Florida, Dept Pharmacotherapy & Translat Res, Gainesville, FL USA;Univ Florida, Ctr Pharmacogen, Gainesville, FL USA.
    Cresci, Sharon
    Washington Univ, Sch Med, Dept Genet, Stat Genom Div, St Louis, MO 63110 USA;Washington Univ, Sch Med, Dept Med, Cardiovasc Div, St Louis, MO 63110 USA.
    de Faire, Ulf
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Doughty, Robert N.
    Univ Auckland, Heart Hlth Res Grp, Auckland, New Zealand.
    Drexel, Heinz
    VIVIT, Feldkirch, Austria;Private Univ Principal Liechtenstein, Triesen, Liechtenstein;Drexel Univ, Coll Med, Philadelphia, PA USA.
    Engert, James C.
    McGill Univ Hlth Ctr, Res Inst, Montreal, PQ, Canada;Royal Victoria Hosp, Dept Med, Div Cardiol, Montreal, PQ, Canada;McGill Univ Hlth Ctr, Prevent & Genom Cardiol, Montreal, PQ, Canada.
    Fox, Keith A. A.
    Univ Edinburgh, Cardiol, Edinburgh, Midlothian, Scotland.
    Girelli, Domenico
    Univ Verona, Dept Med, Verona, Italy.
    Hagström, Emil
    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.
    Hazen, Stanley L.
    Cleveland Clin, Lerner Res Inst, Dept Cellular & Mol Med, Cleveland, OH 44106 USA;Cleveland Clin, Dept Cardiovasc Med, Heart & Vasc Inst, Cleveland, OH 44106 USA;Cleveland Clin, Dept Cardiovasc Med, Ctr Microbiome & Human Hlth, Cleveland, OH 44106 USA.
    Held, Claes
    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.
    Hemingway, Harry
    UCL, Inst Hlth Informat, Fac Populat Hlth Sci, London, England.
    Hoefer, Imo E.
    UMC, Dept Clin Chem & Hematol, Utrecht, Netherlands.
    Hovingh, G. Kees
    Acad Med Ctr, Dept Vasc Med, Amsterdam, Netherlands.
    Johnson, Julie A.
    Univ Florida, Dept Pharmacotherapy & Translat Res, Gainesville, FL USA;Univ Florida, Ctr Pharmacogen, Gainesville, FL USA;Univ Florida, Coll Med, Div Cardiovasc Med, Gainesville, FL USA.
    De Jong, Pim A.
    Univ Med Ctr, Dept Radiol, Utrecht, Netherlands.
    Jukema, J. Wouter
    Univ Utrecht, Dept Cardiol, Utrecht, Netherlands;Inter Univ, Cardiol Inst Netherlands, Utrecht, Netherlands.
    Kaczor, Marcin P.
    Jagiellonian Univ, Med Coll, Dept Internal Med, Krakow, Poland.
    Kahonen, Mika
    Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Ctr, Dept Clin Physiol, Tampere, Finland;Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland.
    Kettner, Jiri
    Inst Clin & Expt Med, Cardiol Ctr, Prague, Czech Republic.
    Kiliszek, Marek
    Mil Inst Med, Dept Cardiol & Internal Dis, Warsaw, Poland.
    Klungel, Olaf H.
    Univ Med Ctr, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands.
    Lagerqvist, Bo
    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.
    Lambrechts, Diether
    Katholieke Univ Leuven, Dept Human Genet, Lab Translat Genet, Leuven, Belgium.
    Laurikka, Jari O.
    Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Ctr, Dept Cardiothorac Surg, Tampere, Finland;Tampere Univ Hosp, Heart Ctr, Dept Cardiothorac Surg, Tampere, Finland.
    Lehtimaki, Terho
    Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Ctr, Dept Clin Chem, Tampere, Finland;Fimlab Labs, Dept Clin Chem, Tampere, Finland.
    Lindholm, Daniel
    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.
    Mahmoodi, Bakhtawar K.
    St Antonius Hosp, Dept Cardiol, Nieuwegein, Netherlands.
    Maitland-van der Zee, Anke H.
    Univ Med Ctr, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands;Univ Amsterdam, Acad Med Ctr, Dept Resp Med, Clin & Expt Cardiol, Amsterdam, Netherlands.
    McPherson, Ruth
    Univ Ottawa Heart Inst, Ottawa, ON, Canada;Univ Ottawa, Dept Med, Ottawa, ON, Canada;Univ Ottawa, Dept Biochem, Ottawa, ON, Canada;Univ Ottawa, Dept Microbiol & Immunol, Ottawa, ON, Canada.
    Melander, Olle
    Lund Univ, Dept Clin Sci, Malmo, Sweden;Skane Univ Hosp, Dept Internal Med, Malmo, Sweden.
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia;Univ Tartu, Inst Mol & Cell Biol, Dept Biotechnol, Tartu, Estonia.
    Pepinski, Witold
    Med Univ Bialystok, Dept Forens Med, Bialystok, Poland.
    Olivieri, Oliviero
    Univ Verona, Dept Med, Verona, Italy.
    Opolski, Grzegorz
    Med Univ Warsaw, Dept Cardiol, Warsaw, Poland.
    Palmer, Colin N.
    Ninewells Hosp & Med Sch, Div Mol & Clin Med, Pat Macpherson Ctr Pharmacogenet & Pharmacogen, Dundee, Scotland.
    Pasterkamp, Gerard
    UMC, Dept Clin Chem, Utrecht, Netherlands.
    Pepine, Carl J.
    Univ Florida, Coll Med, Div Cardiovasc Med, Gainesville, FL USA.
    Pereira, Alexandre C.
    Univ Sao Paulo, Heart Inst, Sao Paulo, Brazil.
    Note, Louise
    Humanitas Univ, Dept Biomed Sci, Milan, Italy.
    Quyyumi, Arshed A.
    Emory Univ, Sch Med, Dept Med, Emory Clin Cardiovasc Res Inst, Atlanta, GA USA.
    Richards, A. Mark
    Univ Otago, Christchurch Heart Inst, Dunedin, New Zealand;Natl Univ Singapore, Cardiovasc Res Inst, Singapore, Singapore.
    Sanak, Marek
    Jagiellonian Univ, Med Coll, Dept Internal Med, Krakow, Poland.
    Scholz, Markus
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sinisalo, Juha
    Univ Helsinki, Helsinki Univ Hosp, Heart & Lung Ctr, Helsinki, Finland.
    Smith, J. Gustav
    Lund Univ, Dept Cardiol Clin Sci, Lund, Sweden;Skane Univ Hosp, Malmo, Sweden;Wallenberg Ctr Mol Med, Malmo, Sweden;Lund Univ, Lund Univ Diabet Ctr, Lund, Sweden.
    Spertus, John A.
    St Lukes Mid Amer Heart Inst, Kansas City, MO USA;Univ Missouri, St Lukes Hlth Syst, Kansas City, MO 64110 USA.
    Stewart, Alexandre F. R.
    Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada;Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON, Canada.
    Szczeklik, Wojciech
    Jagiellonian Univ, Med Coll, Dept Internal Med, Krakow, Poland.
    Szpakowicz, Anna
    Med Univ Bialystok, Dept Cardiol, Bialystok, Poland.
    ten Berg, Jurrien M.
    Intertermt Med Ctr, Intermt Heart Inst, Salt Lake City, UT USA;St Antonius Hosp, Dept Cardiol, Nieuwegein, Netherlands.
    Thanassoulis, George
    Med Univ Bialystok, Dept Forens Med, Bialystok, Poland;Royal Victoria Hosp, Dept Med, Div Cardiol, Montreal, PQ, Canada;McGill Univ Hlth Ctr, Prevent & Genom Cardiol, Montreal, PQ, Canada.
    Thieiy, Joachim
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Univ Hosp, Clin Chem & Mol Diagnost, Inst Lab Med, Leipzig, Germany.
    van der Graaf, Yolanda
    Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
    Visseren, Frank L. J.
    McGill Univ Hlth Ctr, Ctr Outcomes Res & Evaluat, Res Inst, Montreal, PQ, Canada.
    Waltenberger, Johannes
    Univ Munster, Dept Cardiovasc Med, Munster, Germany.
    Van der Harst, Pim
    Univ Groningen, Univ Med Ctr, Groningen, Netherlands.
    Tardif, Jean-Claude
    Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada;Univ Montreal, Fac Med, Montreal, PQ, Canada.
    Sattar, Naveed
    Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
    Lang, Chim C.
    Univ Dundee, Sch Med, Div Mol & Clin Med, Dundee, Scotland.
    Pare, Guillaume
    McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada;Populat Hlth Res Inst, Hamilton, ON, Canada.
    Brophy, James M.
    McGill Univ Hlth Ctr, Res Inst, Montreal, PQ, Canada.
    Anderson, Jeffrey L.
    Intertermt Med Ctr, Intermt Heart Inst, Salt Lake City, UT USA;Univ Utah, Dept Internal Med, Cardiol Div, Salt Lake City, UT 84112 USA.
    Maerz, Winfried
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Mannheim, Germany;Synlab Holding Deutschland GmbH, Synlab Acad, Mannheim, Germany;Med Univ Graz, Clin Inst Med, Graz, Austria;Med Univ Graz, Chem Lab Diagnost, Graz, Austria.
    Wallentin, Lars
    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.
    Cameron, Vicky A.
    Univ Otago, Christchurch Heart Inst, Dunedin, New Zealand.
    Horne, Benjamin D.
    UMC, Lab Expt Cardiol, Utrecht, Netherlands;Univ Utah, Dept Biomed Informat, Salt Lake City, UT USA.
    Samani, Nilesh J.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England;Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
    Hingorani, Aroon D.
    UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England.
    Asselbergs, Folkert W.
    UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England;UCL, Inst Hlth Informat, Fac Populat Hlth Sci, London, England;UMC, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands.
    Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events: A GENIUS-CHD Study of Individual Participant Data2019In: Circulation: Genomic and Precision Medicine, ISSN 2574-8300, Vol. 12, no 4, article id e002471Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.

    METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.

    RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).

    CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.

  • 38.
    Patel, Riyaz S.
    et al.
    UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England;St Bartholomews Hosp, Barts Heart Ctr, London, England.
    Tragante, Vinicius
    UMC Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands.
    Schmidt, Amand F.
    UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England;UMC Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands.
    McCubrey, Raymond O.
    Intermt Med Ctr, Intermt Heart Inst, Salt Lake City, UT USA.
    Holmes, Michael, V
    Univ Oxford, Nuffield Dept Populat Hlth, Med Res Council Populat Hlth Res Unit, Clin Trial Serv Unit, Oxford, England;Univ Oxford, Nuffield Dept Populat Hlth, Med Res Council Populat Hlth Res Unit, Epidemiol Studies Unit, Oxford, England;Oxford Univ Hosp, Natl Inst Hlth Res, Oxford Biomed Res Ctr, Oxford, England.
    Howe, Laurence J.
    UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England.
    Direk, Kenan
    UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England;UMC Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands.
    Åkerblom, Axel
    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.
    Leander, Karin
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Virani, Salim S.
    Michael E DeBakey VA Med Ctr, Sect Cardiol, Houston, TX USA;Baylor Coll Med, Sect Cardiovasc Res, Dept Med, Houston, TX 77030 USA.
    Kaminski, Karol A.
    Med Univ Bialystok, Dept Populat Med & Civilizat Dis Prevent, Bialystok, Poland;Med Univ Bialystok, Dept Cardiol, Bialystok, Poland.
    Muehlschlegel, Jochen D.
    Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Allayee, Hooman
    USC, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA;USC, Keck Sch Med, Dept Biochem, Los Angeles, CA USA;USC, Keck Sch Med, Dept Mol Med, Los Angeles, CA USA.
    Almgren, Peter
    Lund Univ, Dept Clin Sci, Malmo, Sweden.
    Alver, Maris
    Univ Tartu, Estonian Genome Ctr, Dept Biotechnol, Inst Genom,Inst Mol & Cell Biol, Tartu, Estonia.
    Baranova, Ekaterina, V
    Univ Utrecht, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands.
    Behloui, Hassan
    McGill Univ, Hlth Ctr, Ctr Outcomes Res & Evaluat, Res Inst, Montreal, PQ, Canada.
    Boeckx, Bram
    Katholieke Univ Leuven, Lab Translat Genet, Dept Human Genet, Leuven, Belgium;VIB Ctr Canc Biol, Lab Translat Genet, Leuven, Belgium.
    Braund, Peter S.
    Univ Leicester, Dept Cardiovasc Sci, BHF Cardiovasc Res Ctr, Leicester, Leics, England;Glenfield Hosp, NIHR Leicester Biomed Res Ctr, Leicester, Leics, England.
    Breitling, Lutz P.
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
    Delgado, Gradela
    Heidelberg Univ, Dept Med 5, Med Fac Mannheim, Heidelberg, Germany.
    Duarte, Nubia E.
    Univ Sao Paulo, Heart Inst, Sao Paulo, Brazil.
    Dube, Marie-Pierre
    Montreal Heart Inst, Montreal, PQ, Canada;Univ Montreal, Fac Med, Montreal, PQ, Canada.
    Dufresne, Line
    McGill Univ, Hlth Ctr, Ctr Outcomes Res & Evaluat, Res Inst, Montreal, PQ, Canada;McGill Univ Hlth Ctr, Prevent & Genom Cardiol, Montreal, PQ, Canada.
    Eriksson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Foco, Luisa
    Univ Lubeck, Inst Biomed, Eurac Res, Affiliated Inst, Bolzano, Italy.
    Scholz, Markus
    Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany;Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany.
    Gijsberts, Crystel M.
    UMC Utrecht, Lab Expt Cardiol, Utrecht, Netherlands.
    Glinge, Charlotte
    Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Heart Ctr, Amsterdam, Netherlands;Univ Amsterdam, Amsterdam UMC, Clin & Expt Cardiol, Amsterdam Cardiovasc Sci,AMC Heart Ctr, Amsterdam, Netherlands.
    Gong, Yan
    Univ Florida, Dept Pharmacotherapy & Translat Res, Ctr Pharmacogen, Gainesville, FL USA.
    Hartiala, Jaana
    USC, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA;USC, Keck Sch Med, Dept Biochem, Los Angeles, CA USA;USC, Keck Sch Med, Dept Mol Med, Los Angeles, CA USA;USC, Keck Sch Med, Inst Genet Med, Los Angeles, CA USA.
    Heydarpour, Mahyar
    Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Hubacek, Jaroslav A.
    Inst Clin & Expt Med, Ctr Expt Med, Prague, Czech Republic.
    Kleber, Marcus
    Heidelberg Univ, Dept Med 5, Med Fac Mannheim, Heidelberg, Germany.
    Kofink, Daniel
    Montreal Heart Inst, Montreal, PQ, Canada.
    Kotti, Salma
    URCEST CRCEST CRB HUEP UPMC, AP HP, Dept Clin Pharmacol, Platform Clin Res East Paris, Paris, France.
    Kuukasjarvi, Pekka
    Univ Tampere, Dept Cardiothorac Surg, Tampere, Finland.
    Lee, Vei-Vei
    Texas Heart Inst, Dept Biostat & Epidemiol, Houston, TX 77025 USA.
    Leiherer, Andreas
    VIVIT, Feldkirch, Austria;Private Univ Principal Liechtenstein, Triesen, Liechtenstein;Med Cent Labs, Feldkirch, Austria.
    Lenzini, Petra A.
    Washington Univ, Sch Med, Dept Genet, Stat Genom Div, St Louis, MO 63110 USA.
    Levin, Daniel
    Univ Dundee, Div Mol & Clin Med, Sch Med, Dundee, Scotland.
    Lyytikainen, Leo-Pekka
    Univ Tampere, Dept Clin Chem, Tampere, Finland;Fimlab Labs, Dept Clin Chem, Tampere, Finland.
    Martinelli, Nicola
    Univ Verona, Dept Med, Verona, Italy.
    Mons, Ute
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
    Nelson, Christopher P.
    Univ Leicester, Dept Cardiovasc Sci, BHF Cardiovasc Res Ctr, Leicester, Leics, England;Glenfield Hosp, NIHR Leicester Biomed Res Ctr, Leicester, Leics, England.
    Nikus, Kjell
    Univ Tampere, Dept Cardiol, Tampere, Finland;Tampere Univ Hosp, Dept Cardiol, Heart Ctr, Tampere, Finland.
    Pilbrow, Anna P.
    Univ Otago, Christchurch Heart Inst, Christchurch, New Zealand.
    Ploski, Rafal
    Med Univ Warsaw, Dept Med Genet, Warsaw, Poland.
    Sun, Yan, V
    Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA;Emory Univ, Sch Med, Dept Biomed Informat, Emory Clin Cardiovasc Res Inst, Atlanta, GA 30322 USA.
    Tanck, Michael W. T.
    Univ Amsterdam, Amsterdam UMC, Clin Epidemiol & Biostat, Amsterdam, Netherlands.
    Tang, W. H. Wilson
    Cleveland Clin, Lerner Res Inst, Dept Cellular & Mol Med, Cleveland, OH 44106 USA;Cleveland Clin, Dept Cardiovasc Med, Heart & Vasc Inst, Cleveland, OH 44106 USA;Cleveland Clin, Ctr Clin Genom, Cleveland, OH 44106 USA.
    Trompet, Stella
    Cleveland Clin, Sect Gerontol & Geriatr, Dept Internal Med, Cleveland, OH 44106 USA;Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands.
    van der Laan, Sander W.
    Univ Utrecht, Div Labs Pharm & Biomed Genet, Lab Clin Chem & Hematol, UMC Utrecht, Utrecht, Netherlands.
    Van Setten, Jessica
    Univ Utrecht, Div Heart & Lungs, Dept Cardiol, UMC Utrecht, Utrecht, Netherlands.
    Vilmundarson, Ragnar O.
    Univ Ottawa, Heart Inst, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada;Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON, Canada.
    Anselmi, Chiara Viviani
    Humanitas Clin & Res Ctr, Dept Cardiovasc Med, Milan, Italy.
    Vlachopoulou, Efthymia
    Helsinki Univ Hosp, Transplantat Lab, Helsinki, Finland;Univ Helsinki, Helsinki, Finland.
    Al Ali, Lawien
    Univ Groningen, Univ Med Ctr, Groningen, Netherlands.
    Boerwinkle, Eric
    Univ Texas Houston, Sch Publ Hlth, Houston, TX USA.
    Briguori, Carlo
    Clin Mediterranea, Naples, Italy.
    Carlquist, John F.
    Intermt Med Ctr, Intermt Heart Inst, Salt Lake City, UT USA;Univ Utah, Cardiol Div, Dept Internal Med, Salt Lake City, UT USA.
    Carruthers, Kathryn F.
    Univ Edinburgh, Cardiovasc Sci, QMRI, Edinburgh, Midlothian, Scotland.
    Casu, Gavino
    Humanitas Clin & Res Ctr, Dept Cardiovasc Med, Milan, Italy;ASSL Nuoro Osped San Francesco, ATS Sardegna, Nuoro, Italy.
    Deanfield, John
    UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England;St Bartholomews Hosp, Barts Heart Ctr, London, England.
    Deloukas, Panos
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Med Sch, London, England;Queen Mary Univ London, Ctr Genom Hlth, London, England.
    Dudbridge, Frank
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
    Engstrom, Thomas
    Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Heart Ctr, Amsterdam, Netherlands;Lund Univ, Dept Cardiol, Lund, Sweden.
    Fitzpatrick, Natalie
    UCL, Inst Hlth Informat, Fac Populat Hlth Sci, London, England.
    Fox, Kim
    Royal Brompton Hosp, Natl Heart & Lung Inst, Imperial Coll, London, England;Royal Brompton Hosp, Natl Heart & Lung Inst, Inst Cardiovasc Med & Sci, London, England.
    Gigante, Bruna
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    James, Stefan
    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.
    Lokki, Marja-Liisa
    Helsinki Univ Hosp, Transplantat Lab, Helsinki, Finland;Univ Helsinki, Helsinki, Finland.
    Lotufo, Paulo A.
    Univ Sao Paulo, Hosp Univ, Ctr Pesquisa Clin, Sao Paulo, Brazil.
    Marziliano, Nicola
    ATS Sardegna, ASL Nuoro 3, Nuoro, Italy.
    Mordi, Ify R.
    Univ Dundee, Div Mol & Clin Med, Sch Med, Dundee, Scotland.
    Muhlestein, Joseph B.
    Intermt Med Ctr, Intermt Heart Inst, Salt Lake City, UT USA;Univ Utah, Cardiol Div, Dept Internal Med, Salt Lake City, UT USA.
    Newton-Cheh, Christopher
    Massachusetts Gen Hosp, Cardiovasc Res Ctr, Ctr Human Genet Res, Boston, MA 02114 USA;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
    Pitha, Jan
    Inst Clin & Expt Med, Ctr Expt Med, Prague, Czech Republic.
    Saely, Christoph H.
    VIVIT, Feldkirch, Austria;Private Univ Principal Liechtenstein, Triesen, Liechtenstein;Acad Teaching Hosp Feldkirch, Dept Med & Cardiol, Feldkirch, Austria.
    Samman-Tahhan, Ayman
    Emory Univ, Sch Med, Div Cardiol, Dept Med,Emory Clin Cardiovasc Res Inst, Atlanta, GA 30322 USA.
    Sandesara, Pratik B.
    Emory Univ, Sch Med, Div Cardiol, Dept Med,Emory Clin Cardiovasc Res Inst, Atlanta, GA 30322 USA.
    Teren, Andrej
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Heart Ctr Leipzig, Leipzig, Germany.
    Timmis, Adam
    UCL, Inst Hlth Informat, Fac Populat Hlth Sci, London, England;St Bartholomews Hosp, Barts Heart Ctr, London, England.
    Van de Werf, Frans
    Katholieke Univ Leuven, Dept Cardiovasc Sci, Leuven, Belgium.
    Wauters, Els
    Univ Hosp KU Leuven, Resp Oncol Unit, Dept Resp Med, Leuven, Belgium.
    Wilde, Arthur A. M.
    Univ Amsterdam, Amsterdam UMC, Clin & Expt Cardiol, Amsterdam Cardiovasc Sci,AMC Heart Ctr, Amsterdam, Netherlands;Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah, Saudi Arabia.
    Ford, Ian
    Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
    Stott, David J.
    Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
    Algra, Ale
    Univ Utrecht, Dept Neurol & Neurosurg, Brain Ctr Rudolf Magnus & Julius Ctr Hlth Sci & P, UMC Utrecht, Utrecht, Netherlands.
    Andreassi, Maria G.
    CNR, Inst Clin Physiol, Pisa, Italy.
    Ardissino, Diego
    Parma Univ Hosp, Cardiol Dept, Parma, Italy.
    Arsenault, Benoit J.
    Inst Univ Cardiol & Pneumol Quebec, Ctr Rech, Quebec City, PQ, Canada;Univ Laval, Dept Med, Fac Med, Laval, PQ, Canada.
    Ballantyne, Christie M.
    Baylor Coll Med, Sect Cardiovasc Res, Dept Med, Houston, TX 77030 USA.
    Bergmeijer, Thomas O.
    St Antonius Hosp, Dept Cardiol, Nieuwegein, Netherlands.
    Bezzina, Connie R.
    Univ Amsterdam, Amsterdam UMC, Clin & Expt Cardiol, Amsterdam Cardiovasc Sci,AMC Heart Ctr, Amsterdam, Netherlands.
    Body, Simon C.
    Harvard Med Sch, Boston, MA 02115 USA;Beth Israel Deaconess Med Ctr, Boston, MA USA.
    Boersma, Eric H.
    Erasmus MC, Dept Cardiol, Thoraxctr, Rotterdam, Netherlands;Erasmus Med Ctr COEUR, Cardiovasc Res Sch, Rotterdam, Netherlands.
    Bogaty, Peter
    Laval Univ, Inst Univ Cardiol & Pneumol Quebec, Quebec City, PQ, Canada.
    Bots, Michiel L.
    Univ Utrecht, Julius Ctr Hlth Sci & Primary Care, UMC Utrecht, Utrecht, Netherlands.
    Brenner, Hermann
    Heidelberg Univ, Network Aging Res, Heidelberg, Germany.
    Brugts, Jasper J.
    Erasmus MC, Dept Cardiol, Thoraxctr, Rotterdam, Netherlands.
    Burkhardt, Ralph
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Univ Hosp Regensburg, Inst Clin Chem & Lab Med, Regensburg, Germany.
    Carpeggiani, Clara
    CNR, Inst Clin Physiol, Pisa, Italy.
    Condorelli, Gianluigi
    Humanitas Univ, Dept Biomed Sci, Milan, Italy.
    Cooper-DeHoff, Rhonda M.
    Univ Florida, Dept Pharmacotherapy & Translat Res, Ctr Pharmacogen, Gainesville, FL USA;Univ Florida, Div Cardiovasc Med, Coll Med, Gainesville, FL USA.
    Cresci, Sharon
    Washington Univ, Sch Med, Dept Genet, Stat Genom Div, St Louis, MO 63110 USA;Washington Univ, Dept Med, Cardiovasc Div, St Louis, MO 63110 USA.
    Danchin, Nicolas
    Univ Paris 05, Hop Europeen Georges Pompidou, AP HP, Dept Cardiol, Paris, France;Univ Paris 05, FACT, Paris, France;Univ Paris 05, Paris, France.
    de Faire, Ulf
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Doughty, Robert N.
    Univ Auckland, Heart Hlth Res Grp, Auckland, New Zealand.
    Drexel, Heinz
    VIVIT, Feldkirch, Austria;Private Univ Principal Liechtenstein, Triesen, Liechtenstein;Drexel Univ, Coll Med, Philadelphia, PA 19104 USA.
    Engert, James C.
    McGill Univ, Res Inst, Hlth Ctr, Montreal, PQ, Canada;McGill Univ Hlth Ctr, Prevent & Genom Cardiol, Montreal, PQ, Canada;McGill Univ Hlth Ctr, Royal Victoria Hosp, Dept Med, Div Cardiol, Montreal, PQ, Canada.
    Fox, Keith A. A.
    Univ Edinburgh, Edinburgh, Midlothian, Scotland.
    Girelli, Domenico
    Univ Verona, Dept Med, Verona, Italy.
    Grobbee, Diederick E.
    Univ Utrecht, Julius Ctr Hlth Sci & Primary Care, UMC Utrecht, Utrecht, Netherlands.
    Hagström, Emil
    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.
    Hazen, Stanley L.
    Cleveland Clin, Lerner Res Inst, Dept Cellular & Mol Med, Cleveland, OH 44106 USA;Cleveland Clin, Dept Cardiovasc Med, Ctr Microbiome & Human Hlth, Heart & Vasc Inst, Cleveland, OH 44106 USA.
    Held, Claes
    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.
    Hemingway, Harry
    UCL, Inst Hlth Informat, Fac Populat Hlth Sci, London, England.
    Hoefer, Imo E.
    UMC Utrecht, Dept Clin Chem & Hematol, Utrecht, Netherlands.
    Hovingh, G. Kees
    Acad Med Ctr, Dept Vasc Med, Amsterdam, Netherlands.
    Jabbari, Reza
    Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Heart Ctr, Amsterdam, Netherlands.
    Johnson, Julie A.
    Univ Florida, Dept Pharmacotherapy & Translat Res, Ctr Pharmacogen, Gainesville, FL USA;Univ Florida, Div Cardiovasc Med, Coll Med, Gainesville, FL USA.
    Jukema, J. Wouter
    Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands;LUMC, Einthoven Lab Expt Vasc Med, Leiden, Netherlands;Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands.
    Kaczor, Marcin P.
    Jagiellonian Univ, Dept Internal Med, Med Coll, Krakow, Poland.
    Kahonen, Mika
    Univ Tampere, Dept Clin Physiol, Tampere, Finland;Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland.
    Kettner, Jiri
    Inst Clin & Expt Med, Cardiol Ctr, Prague, Czech Republic.
    Kiliszek, Marek
    Mil Inst Med, Dept Cardiol & Internal Dis, Warsaw, Poland.
    Klungel, Olaf H.
    Univ Utrecht, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands.
    Lagerqvist, Bo
    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.
    Lambrechts, Diether
    Katholieke Univ Leuven, Lab Translat Genet, Dept Human Genet, Leuven, Belgium;VIB Ctr Canc Biol, Lab Translat Genet, Leuven, Belgium.
    Laurikka, Jari O.
    Univ Tampere, Dept Cardiothorac Surg, Finnish Cardiovasc Res Ctr, Fac Med & Life Sci, Tampere, Finland;Tampere Univ Hosp, Dept Cardio Thorac Surg, Heart Ctr, Tampere, Finland.
    Lehtimaki, Terho
    Univ Tampere, Dept Clin Chem, Tampere, Finland;Fimlab Labs, Dept Clin Chem, Tampere, Finland.
    Lindholm, Daniel
    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.
    Mahmoodi, B. K.
    St Antonius Hosp, Dept Cardiol, Nieuwegein, Netherlands.
    Maitland-van der Zee, Anke H.
    Univ Utrecht, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands;Univ Amsterdam, Dept Resp Med, Acad Med Ctr, Amsterdam, Netherlands.
    McPherson, Ruth
    Univ Ottawa, Heart Inst, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada;Univ Ottawa, Dept Med, Ottawa, ON, Canada;Univ Ottawa, Dept Biochem, Ottawa, ON, Canada;Univ Ottawa, Dept Microbiol & Immunol, Ottawa, ON, Canada.
    Melander, Olle
    Lund Univ, Dept Clin Sci, Malmo, Sweden;Skane Univ Hosp, Dept Internal Med, Malmo, Sweden.
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Dept Biotechnol, Inst Genom,Inst Mol & Cell Biol, Tartu, Estonia.
    Niemcunowicz-Janica, Anna
    Med Univ Bialystok, Dept Forens Med, Bialystok, Poland.
    Olivieri, Oliviero
    Univ Verona, Dept Med, Verona, Italy.
    Opolski, Grzegorz
    Med Univ Warsaw, Chair 1, Warsaw, Poland;Med Univ Warsaw, Dept Cardiol, Warsaw, Poland.
    Palmer, Colin N.
    Ninewells Hosp & Med Sch, Pat Macpherson Ctr Pharmacogenet & Pharmacogen, Div Mol & Clin Med, Dundee, Scotland.
    Pasterkamp, Gerard
    UMC Utrecht, Dept Clin Chem, Utrecht, Netherlands.
    Pepine, Carl J.
    Univ Florida, Div Cardiovasc Med, Coll Med, Gainesville, FL USA.
    Pereira, Alexandre C.
    Univ Sao Paulo, Heart Inst, Sao Paulo, Brazil.
    Pilote, Louise
    McGill Univ, Hlth Ctr, Ctr Outcomes Res & Evaluat, Res Inst, Montreal, PQ, Canada;McGill Univ Hlth Ctr, Dept Med, Montreal, PQ, Canada.
    Quyyumi, Arshed A.
    Emory Univ, Sch Med, Div Cardiol, Dept Med,Emory Clin Cardiovasc Res Inst, Atlanta, GA 30322 USA.
    Richards, A. Mark
    Univ Otago, Christchurch Heart Inst, Christchurch, New Zealand;Natl Univ Singapore, Cardiovasc Res Inst, Singapore, Singapore.
    Sanak, Marek
    Jagiellonian Univ, Dept Internal Med, Med Coll, Krakow, Poland.
    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, Clinical Chemistry.
    Simon, Tabassome
    Sorbonne Univ, Platform Clin Res East Paris URCEST CRCEST CRB HU, Dept Clin Pharmacol, AP HP,FACT, Paris, France;Paris Sorbonne Univ, UPMC Site St Antoine, Paris, France.
    Sinisalo, Juha
    Heart and Lung Centre (J.S.), Helsinki University Hospital and University of Helsinki, Finland.
    Smith, J. Gustav
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA;Lund Univ, Dept Cardiol Clin Sci, Skane Univ Hosp, Lund, Sweden;Lund Univ, Wallenberg Ctr Mol Med, Diabet Ctr, Lund, Sweden.
    Spertus, John A.
    Univ Missouri, St Lukes Mid Amer Heart Inst, Kansas City, MO 64110 USA;St Lukes Mid Amer Heart Insti, Kansas City, MO USA.
    Stender, Steen
    Copenhagen Univ Hosp, Dept Clin Biochem, Gentofte, Denmark.
    Stewart, Alexandre F. R.
    Univ Ottawa, Heart Inst, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada;Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON, Canada.
    Szczeklik, Wojciech
    Jagiellonian Univ, Dept Internal Med, Med Coll, Krakow, Poland.
    Szpakowicz, Anna
    Med Univ Bialystok, Dept Cardiol, Bialystok, Poland.
    Tardif, Jean-Claude
    Montreal Heart Inst, Montreal, PQ, Canada;Univ Montreal, Fac Med, Montreal, PQ, Canada.
    ten Berg, Jurrien M.
    St Antonius Hosp, Dept Cardiol, Nieuwegein, Netherlands.
    Tfelt-Hansen, Jacob
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Heart Ctr, Copenhagen, Denmark;Univ Copenhagen, Fac Med Sci, Dept Forens Med, Copenhagen, Denmark.
    Thanassoulis, George
    McGill Univ, Hlth Ctr, Ctr Outcomes Res & Evaluat, Res Inst, Montreal, PQ, Canada;McGill Univ Hlth Ctr, Prevent & Genom Cardiol, Montreal, PQ, Canada;McGill Univ Hlth Ctr, Royal Victoria Hosp, Dept Med, Div Cardiol, Montreal, PQ, Canada.
    Thiery, Joachim
    Univ Hosp, Inst Lab Med, Clin Chem & Mol Diagnost, Leipzig, Germany.
    Torp-Pedersen, Christian
    Aalborg Univ Hosp, Dept Hlth Sci & Technol, Unit Epidemiol & Biostat, Aalborg, Denmark.
    van der Graaf, Yolanda
    Univ Utrecht, Julius Ctr Hlth Sci & Primary Care, UMC Utrecht, Utrecht, Netherlands.
    Visseren, Frank L. J.
    Univ Utrecht, Dept Vasc Med, UMC Utrecht, Utrecht, Netherlands.
    Waltenberger, Johannes
    Univ Munster, Dept Cardiovasc Med, Munster, Germany.
    Weeke, Peter E.
    Herlev & Gentofte Hosp, Dept Cardiol, Hellerup, Denmark.
    Van der Harst, Pim
    Univ Groningen, Univ Med Ctr, Groningen, Netherlands.
    Lang, Chim C.
    Univ Dundee, Div Mol & Clin Med, Sch Med, Dundee, Scotland.
    Sattar, Naveed
    Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
    Cameron, Vicky A.
    Univ Otago, Christchurch Heart Inst, Christchurch, New Zealand.
    Anderson, Jeffrey L.
    Intermt Med Ctr, Intermt Heart Inst, Salt Lake City, UT USA;Univ Utah, Cardiol Div, Dept Internal Med, Salt Lake City, UT USA.
    Brophy, James M.
    McGill Univ, Hlth Ctr, Ctr Outcomes Res & Evaluat, Res Inst, Montreal, PQ, Canada;McGill Univ Hlth Ctr, Dept Med, Montreal, PQ, Canada.
    Pare, Guillaume
    McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada;Populat Hlth Res Inst, Hamilton, ON, Canada.
    Horne, Benjamin D.
    Intermt Med Ctr, Intermt Heart Inst, Salt Lake City, UT USA;Univ Utah, Dept Biomed Informat, Salt Lake City, UT USA.
    Marz, Winfried
    Heidelberg Univ, Dept Med 5, Med Fac Mannheim, Heidelberg, Germany;Synlab Holding Deutschland GmbH, Synlab Acad, Mannheim, Germany;Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria.
    Wallentin, Lars
    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.
    Samani, Nilesh J.
    Univ Leicester, Dept Cardiovasc Sci, BHF Cardiovasc Res Ctr, Leicester, Leics, England;Glenfield Hosp, NIHR Leicester Biomed Res Ctr, Leicester, Leics, England.
    Hingorani, Aroon D.
    Institute of Cardiovascular Science, Faculty of Population Health Science, University College London, United Kingdom.
    Asselbergs, Folkert W.
    UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England;UCL, Inst Hlth Informat, Fac Populat Hlth Sci, London, England;UMC Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands;ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.
    Subsequent Event Risk in Individuals With Established Coronary Heart Disease: Design and Rationale of the GENIUS-CHD Consortium2019In: Circulation: Genomic and Precision Medicine, ISSN 2574-8300, Vol. 12, no 4, article id e002470Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.

    METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.

    RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.

    CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.

  • 39.
    Rerup, S. N. A. A.
    et al.
    Copenhagen Univ Hosp, Rigshosp, Ctr Heart, Copenhagen, Denmark..
    Bang, L. E.
    Copenhagen Univ Hosp, Rigshosp, Ctr Heart, Copenhagen, Denmark..
    Mogensen, U. M.
    Copenhagen Univ Hosp, Rigshosp, Ctr Heart, Copenhagen, Denmark..
    Engstroem, T.
    Copenhagen Univ Hosp, Rigshosp, Ctr Heart, Copenhagen, Denmark..
    Pedersen, F.
    Copenhagen Univ Hosp, Rigshosp, Ctr Heart, Copenhagen, Denmark..
    Joergensen, E.
    Copenhagen Univ Hosp, Rigshosp, Ctr Heart, Copenhagen, Denmark..
    Torp-Pedersen, C.
    Aalborg Univ Hosp, Dept Social Med, Aalborg, Denmark..
    Gislason, G.
    Gentofte Univ Hosp, Dept Cardiol, Gentofte, Denmark..
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Koeber, L.
    Copenhagen Univ Hosp, Rigshosp, Ctr Heart, Copenhagen, Denmark..
    Fosboel, E.
    Copenhagen Univ Hosp, Rigshosp, Ctr Heart, Copenhagen, Denmark..
    The prevalence and prognostic importance of possible familial hypercholesterolemia in patients with myocardial infarction2016In: EUROPEAN HEART JOURNAL, ISSN 0195-668X, Vol. 37, p. 141-141Article in journal (Refereed)
  • 40.
    Ridefelt, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Hagström, Emil
    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.
    Svensson, Maria K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Åkerfeldt, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Age- and sex-specific reference values for non-HDL cholesterol and remnant cholesterol derived from the Nordic Reference Interval Project (NORIP).2019In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Non-HDL-cholesterol (non-HDL-C) has been reported to be a better marker of cardiovascular risk than LDL-cholesterol (LDL-C) especially in individuals with high triglyceride values. Further, levels of remnant cholesterol have been suggested to in part explain residual risk not captured with LDL-C. The aim of the present study was to define reference values for non-HDL-C and remnant cholesterol based on data from the Nordic Reference Interval Project (NORIP).

    METHODS: We analyzed the test results for total cholesterol, HDL-cholesterol and triglycerides from 1392 healthy females and 1236 healthy males. Non-HDL-C was calculated as measured total cholesterol minus measured HDL-cholesterol. Remnant cholesterol was calculated using the Friedewald equation for LDL-C: measured total cholesterol minus measured HDL-cholesterol and minus calculated LDL-cholesterol. The 2.5th and 97.5th percentiles for these markers were calculated according to the International Federation of Clinical Chemistry guidelines on the statistical treatment of reference values.

    RESULTS: Age (18-<30, 30-49 and ≥50 years) and sex-specific reference intervals were calculated for non-HDL-cholesterol and remnant-cholesterol. Levels of non-HDL-C and remnant cholesterol differed between sex and age strata.

    CONCLUSIONS: Age- and sex-specific reference intervals should be used for the triglyceride rich lipid variables non-HDL-C and remnant cholesterol. Since these markers may add information on risk burden beyond LDL-C, our hope is that these reference intervals will aid the introduction of automatic reporting of non-HDL-C by hospital laboratories.

  • 41.
    Siegbahn, Agneta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    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.
    Eriksson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Åkerblom, Axel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Bertilsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Axelsson, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Barratt, Bryan J.
    Becker, Richard C.
    Himmelmann, Anders
    James, Stefan K.
    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.
    Katus, Hugo A.
    Steg, Philippe G.
    Storey, Robert F.
    Syvanen, Ann-Christine
    Wallentin, Lars
    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.
    Evaluation of the Effect of Interleukin 18 Associated Genetic Polymorphisms on Risk of Cardiovascular Events in Patients With Acute Coronary Syndrome2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, no 22Article in journal (Other academic)
  • 42. Sinnaeve, Peter R.
    et al.
    Hagström, Emil
    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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Armstrong, Paul
    Budaj, Andrzej
    Elisaf, Moses
    Granger, Christopher
    Held, Claes
    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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare.
    Koenig, Wolfgang
    Pedersen, Terje
    Stebbins, Amanda
    Steg, Philippe
    Stewart, Ralph
    Teramoto, Tamio
    Tse, Hung-Fat
    Wallentin, Lars
    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.
    Watson, David
    White, Harvey
    Diabetes Mellitus And Cardiovascular Risk In Patients With Chronic Coronary Heart Disease2016In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 67, no 13, p. 2162-2162Article in journal (Other academic)
  • 43.
    Stewart, R. A. H.
    et al.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand..
    Armstrong, P. W.
    Univ Alberta, Canadian Vigour Ctr, Edmonton, AB, Canada..
    Chiswell, K.
    Duke Univ, Duke Clin Res Inst, Durham, NC 27706 USA..
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Held, Claes
    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.
    Krug-Gourley, S.
    GlaxoSmithKline, Metab Pathways & Cardiovasc Therapeut Area, King, WI USA..
    Ryan, C. M.
    Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA..
    Stebbins, A.
    Duke Univ, Duke Clin Res Inst, Durham, NC 27706 USA..
    Wallentin, L.
    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.
    White, H. D.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand..
    Effect of ivabradine on heart rate variability in patients with stable coronary artery disease2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no 1 Supplement, p. 1088-1088Article in journal (Other academic)
  • 44.
    Stewart, Ralph A H
    et al.
    Auckland City Hosp, Auckland, New Zealand.
    Hagström, Emil
    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.
    Held, Claes
    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.
    Wang, Tom Kai Ming
    Auckland City Hosp, Auckland, New Zealand.
    Armstrong, Paul W
    Univ Alberta, Canadian VIGOUR Ctr, Edmonton, AB, Canada.
    Aylward, Philip E
    Flinders Univ & Med Ctr, South Australian Hlth & Med Res Inst, Adelaide, SA, Australia.
    Cannon, Christopher P
    Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA..
    Koenig, Wolfgang
    Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany.;Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, Ulm, Germany..
    López-Sendón, José Luis
    Hosp Univ La Paz IdiPaz, Madrid, Spain..
    Mohler, Emile R
    Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA..
    Hadziosmanovic, Nermin
    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.
    Krug-Gourley, Susan
    GlaxoSmithKline, Metab Pathways & Cardiovasc Therapeut Area, King Of Prussia, PA USA..
    Ramos Corrales, Marco Antonio
    San Jose Satelite Hosp, Naucalpan De Juarez, Mexico..
    Siddique, Saulat
    Punjab Med Ctr, Jail Rd, Lahore, Punjab, Pakistan..
    Steg, Philippe Gabriel
    Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, Paris, France.;Diderot Univ, Sorbonne Paris Cite, Paris, France.;Royal Brompton Hosp, ICMS, NHLI Imperial Coll, London, England.;FACT, INSERM, U1148, Paris, France..
    White, Harvey D
    Auckland City Hosp, Auckland, New Zealand..
    Wallentin, Lars
    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.
    Self-Reported Health and Outcomes in Patients With Stable Coronary Heart Disease2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 8, article id e006096Article in journal (Refereed)
    Abstract [en]

    Background-—The major determinants and prognostic importance of self-reported health in patients with stable coronary heartdisease are uncertain.

    Methods and Results-—The STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trialrandomized 15 828 patients with stable coronary heart disease to treatment with darapladib or placebo. At baseline, 98% ofparticipants completed a questionnaire that included the question, “Overall, how do you feel your general health is now?”Possible responses were excellent, very good, good, average, and poor. Adjudicated major adverse cardiac events, whichincluded cardiovascular death, myocardial infarction, and stroke, were evaluated by Cox regression during 3.7 years of follow-upfor participants who reported excellent or very good health (n=2304), good health (n=6863), and average or poor health(n=6361), before and after adjusting for 38 covariates. Self-reported health was most strongly associated with geographicregion, depressive symptoms, and low physical activity (P<0.0001 for all). Poor/average compared with very good/excellentself-reported health was independently associated with major adverse cardiac events (hazard ratio [HR]: 2.30 [95% confidenceinterval (CI), 1.92–2.76]; adjusted HR: 1.83 [95% CI, 1.51–2.22]), cardiovascular mortality (HR: 4.36 [95% CI, 3.09–6.16];adjusted HR: 2.15 [95% CI, 1.45–3.19]), and myocardial infarction (HR: 1.87 [95% CI, 1.46–2.39]; adjusted HR: 1.68 [95% CI,1.25–2.27]; P<0.0002 for all).

    Conclusions-—Self-reported health is strongly associated with geographical region, mood, and physical activity. In a globalcoronary heart disease population, self-reported health was independently associated with major cardiovascular events andmortality beyond what is measurable by established risk indicators.

  • 45.
    Stewart, Ralph A. H.
    et al.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Pk Rd, Auckland 1142, New Zealand..
    Held, Claes
    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.
    Hadziosmanovic, Nermin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Armstrong, Paul W.
    Univ Alberta, Canadian Vigour Ctr, Edmonton, AB, Canada..
    Cannon, Christopher P.
    Brigham & Womens Hosp, Cardiovasc Div, Boston, MA USA..
    Granger, Christopher B.
    Duke Med, Duke Clin Res Inst, Durham, NC USA..
    Hagström, Emil
    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.
    Hochman, Judith S.
    NYU, Dept Med, Langone Med Ctr, New York, NY 10016 USA..
    Koenig, Wolfgang
    Univ Ulm, Dept Internal Med Cardiol 2, Med Ctr, Ulm, Germany.;Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany.;Partner Site Munich Heart Alliance, German Ctr Cardiovasc Res, Munich, Germany..
    Lonn, Eva
    McMaster Univ, Dept Med, Hamilton, ON, Canada.;McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Nicolau, Jose C.
    Univ Sao Paulo, Heart Inst InCor, Med Sch, Sao Paulo, Brazil..
    Steg, Philippe Gabriel
    Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE Fibrosis Inflammat REmodeling, Paris, France.;Paris Diderot Univ, Sorbonne Paris Cite, Paris, France.;Royal Brompton Hosp, Inst Cardiovasc Med & Sci, Imperial Coll, Natl Heart & Lung Inst, London, England.;INSERM, U1148, French Clin Res Infrastruct Network, French Alliance Cardiovasc Trials, Paris, France..
    Vedin, Ola
    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.
    Wallentin, Lars
    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.
    White, Harvey D.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Pk Rd, Auckland 1142, New Zealand..
    Physical Activity and Mortality in Patients With Stable Coronary Heart Disease2017In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 70, no 14, p. 1689-1700Article in journal (Refereed)
    Abstract [en]

    BACKGROUND Recommendations for physical activity in patients with stable coronary heart disease (CHD) are based on modest evidence.

    OBJECTIVES The authors analyzed the association between self-reported exercise and mortality in patients with stable CHD.

    METHODS A total of 15,486 patients from 39 countries with stable CHD who participated in the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) study completed questions at baseline on hours spent each week taking mild, moderate, and vigorous exercise. Associations between the volume of habitual exercise in metabolic equivalents of task hours/week and adverse outcomes during a median follow-up of 3.7 years were evaluated.

    RESULTS A graded decrease in mortality occurred with increased habitual exercise that was steeper at lower compared with higher exercise levels. Doubling exercise volume was associated with lower all-cause mortality (unadjusted hazard ratio [HR]: 0.82; 95% confidence interval [CI]: 0.79 to 0.85; adjusting for covariates, HR: 0.90; 95% CI: 0.87 to 0.93). These associations were similar for cardiovascular mortality (unadjusted HR: 0.83; 95% CI: 0.80 to 0.87; adjusted HR: 0.92; 95% CI: 0.88 to 0.96), but myocardial infarction and stroke were not associated with exercise volume after adjusting for covariates. The association between decrease in mortality and greater physical activity was stronger in the subgroup of patients at higher risk estimated by the ABC-CHD (Age, Biomarkers, Clinical-Coronary Heart Disease) risk score (p for interaction = 0.0007).

    CONCLUSIONS In patients with stable CHD, more physical activity was associated with lower mortality. The largest benefits occurred between sedentary patient groups and between those with the highest mortality risk.

  • 46.
    Stewart, Ralph A. H.
    et al.
    Univ Auckland, Auckland City Hosp, Green Lane Cardiovasc Serv, Private Bag 92024, Auckland 1030, New Zealand..
    Wallentin, Lars
    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.
    Benatar, Jocelyne
    Univ Auckland, Auckland City Hosp, Green Lane Cardiovasc Serv, Private Bag 92024, Auckland 1030, New Zealand..
    Danchin, Nicolas
    Univ Paris 05, Hop Europeen Georges Pompidou, AP HP, INSERM,U970, Paris, France..
    Hagström, Emil
    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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Held, Claes
    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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare.
    Husted, Steen
    Hosp Unit West, Dept Med, Herning Holstebro, Denmark..
    Lönn, Eva
    McMaster Univ, Dept Med, Hamilton, ON, Canada.;McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Stebbins, Amanda
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA..
    Chiswell, Karen
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA..
    Vedin, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Watson, David
    GlaxoSmithKline, Metab Pathways & Cardiovasc Therapeut Area, Res Triangle Pk, NC USA..
    White, Harvey D.
    Univ Auckland, Auckland City Hosp, Green Lane Cardiovasc Serv, Private Bag 92024, Auckland 1030, New Zealand..
    Dietary patterns and the risk of major adverse cardiovascular events in a global study of high-risk patients with stable coronary heart disease2016In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 37, no 25, p. 1993-2001Article in journal (Refereed)
    Abstract [en]

    Objectives To determine whether dietary pattern assessed by a simple self-administered food frequency questionnaire is associated with major adverse cardiovascular events (MACE) in high-risk patients with stable coronary artery disease. Background A Mediterranean dietary pattern has been associated with lower cardiovascular (CV) mortality. It is less certain whether foods common in western diets are associated with CV risk. Methods At baseline, 15 482 (97.8%) patients (mean age 67 +/- 9 years) with stable coronary heart disease from 39 countries who participated in the Stabilisation of atherosclerotic plaque by initiation of darapladib therapy (STABILITY) trial completed a life style questionnaire which included questions on common foods. A Mediterranean diet score (MDS) was calculated for increasing consumption of whole grains, fruits, vegetables, legumes, fish, and alcohol, and for less meat, and a 'Western diet score' (WDS) for increasing consumption of refined grains, sweets and deserts, sugared drinks, and deep fried foods. A multi-variable Cox proportional hazards models assessed associations between MDS or WDS and MACE, defined as CV death, non-fatal myocardial infarction, or non-fatal stroke. Results After a median follow-up of 3.7 years MACE occurred in 7.3% of 2885 subjects with an MDS >= 15, 10.5% of 4018 subjects with an MDS of 13-14, and 10.8% of 8579 subjects with an MDS <= 12. A one unit increase in MDS > 12 was associated with lower MACE after adjusting for all covariates (+1 category HR 0.95, 95% CI 0.91, 0.98, P = 0.002). There was no association between WDS (adjusted model +1 category HR 0.99, 95% CI 0.97, 1.01) and MACE. Conclusion Greater consumption of healthy foods may be more important for secondary prevention of coronary artery disease than avoidance of less healthy foods typical of Western diets.

  • 47. Stewart, Ralph Alan Huston
    et al.
    Hagström, Emil
    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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Held, Claes
    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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare.
    Armstrong, Paul
    Aylward, Philip
    Cannon, Christopher
    Koenig, Wolfgang
    Lopez-Sendon, Jose
    Mohler, Emile
    Hadziosmanovic, Nermin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Krug-Gourley, Susan
    Siddique, Saulat
    Steg, Philippe
    White, Harvey
    Wallentin, Lars
    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.
    Self-Reported General Health And Outcomes In Patients With Stable Coronary Artery Disease: Experiences From The Global Stability Trial2016In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 67, no 13, p. 2113-2113Article in journal (Other academic)
  • 48. Stewart, Ralph
    et al.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Brown, Rebekkah
    Vedin, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lonn, Eva
    Armstrong, Paul
    Granger, Christopher B.
    Hochman, Judith
    Davies, Richard
    Soffer, Joseph
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    White, Harvey
    Physical activity in patients with stable coronary heart disease: an international perspective2013In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no 42, p. 3286-3293Article in journal (Refereed)
    Abstract [en]

    Aims Despite the known benefits of regular exercise, the reasons why many coronary heart disease (CHD) patients engage in little physical activity are not well understood. This study identifies factors associated with low activity levels in individuals with chronic CHD participating in the STABILITY study, a global clinical outcomes trial evaluating the lipoprotein phospholipaseA2 inhibitor darapladib.

    Methods and results Prior to randomization, 15 486 (97.8%) participants from 39 countries completed a lifestyle questionnaire. Total physical activity was estimated from individual subject self-reports of hours spend each week on mild, moderate, and vigorous exercise, corresponding approximately to 2, 4, and 8 METS, respectively. Multivariate logistic regression evaluated clinical and demographic variables for the lowest compared with higher overall exercise levels, and for individuals who decreased rather than maintained or increased activity since diagnosis of CHD. The least active 5280 subjects (34%) reported exercise of ≤24MET.h/week. A total of 7191 subjects (46%) reported less exercise compared with before diagnosis of CHD. The majority of participants were either ‘not limited’ or ‘limited a little’ walking 100 m (84%), climbing one flight of stairs (82%), or walking 1 km/½ mile (68%), and <10% were limited ‘a lot’ by dyspnoea or angina. Variables independently associated with both low physical activity and decreasing exercise after diagnosis of CHD included more co-morbid conditions, poorer general health, fewer years of education, race, and country (P < 0.001 for all).

    Conclusion In this international study, low physical activity was only partly explained by cardiovascular symptoms. Potentially modifiable societal and health system factors are important determinants of physical inactivity in patients with chronic CHD.

  • 49.
    Varenhorst, Christoph
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Eriksson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Johansson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Barratt, Bryan J.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Åkerblom, Axel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Becker, Richard C.
    James, Stefan K.
    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.
    Katus, Hugo A.
    Husted, Steen
    Steg, Ph. Gabriel
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Voora, Deepak
    Teng, Renli
    Storey, Robert F.
    Wallentin, Lars
    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.
    Effect of genetic variations on ticagrelor plasma levels and clinical outcomes2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no 29, p. 1901-1912Article in journal (Refereed)
    Abstract [en]

    Aims Ticagrelor, a direct-acting P2Y(12)-receptor antagonist, is rapidly absorbed and partly metabolized to the major metabolite AR-C124910XX (ARC). To identify single-nucleotide polymorphisms (SNPs) associated with pharmacokinetics of ticagrelor and clinical outcomes, we performed a genome-wide association study (GWAS) in patients treated with ticagrelor in the PLATO trial. Methods and results A two-stage design was used for the GWAS with discovery (discovery phase: n = 1812) and replication cohorts (replication phase: n = 1941). The steady-state area under the curve (AUCss) values, estimated by the population pharmacokinetic (PK) models, were log transformed and analysed on a genome-wide scale using linear regression. SNPs were analysed against clinical events using Cox-regression in 4990 patients. An SNP (rs113681054) in SLCO1B1 was associated with levels of ticagrelor (P = 1.1 x 10(-6)) and ARC (P = 4.6 x 10(-13)). This SNP is in linkage disequilibrium with a functional variant (rs4149056) that results in decreased OATP1B1 transporter activity. Ticagrelor levels were also associated with two independent SNPs (rs62471956, P = 7.7 x 10(-15) and rs56324128, P = 9.7 x 10(-12)) in the CYP3A4 region. Further, ARC levels were associated with rs61361928 (P = 3.0 x 10(-14)) in UGT2B7. At all loci, the effects were small. None of the identified SNPs that affected ticagrelor PK were associated with the primary composite outcome (cardiovascular death myocardial infarction, and stroke), non-CABG-related bleeds or investigator-reported dyspnoea. Conclusion In patients with ACS, ticagrelor pharmacokinetics is influenced by three genetic loci (SLCO1B1, UGT2B7, and CYP3A4). However, the modest genetic effects on ticagrelor plasma levels did not translate into any detectable effect on efficacy or safety during ticagrelor treatment.

  • 50.
    Vedin, Ola
    et al.
    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.
    Hagström, Emil
    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.
    Budaj, Andrzej
    Denchev, Stephan
    Harrington, Robert A
    Koenig, Wolfgang
    Soffer, Joseph
    Sritara, Piyamitr
    Stebbins, Amanda
    Stewart, Ralph Ha
    Swart, Henk P
    Viigimaa, Margus
    Vinereanu, Dragos
    Wallentin, Lars
    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.
    White, Harvey D
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Held, Claes
    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.
    Tooth loss is independently associated with poor outcomes in stable coronary heart disease.2016In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 23, no 8, p. 839-846Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: We investigated associations between self-reported tooth loss and cardiovascular outcomes in a global stable coronary heart disease cohort.

    METHODS: We examined 15,456 patients from 39 countries with stable coronary heart disease (prior myocardial infarction, prior revascularisation or multivessel coronary heart disease) in the STABILITY trial. At baseline, patients reported number of teeth (26-32 (all), 20-25, 15-19, 1-14 and no teeth) and were followed for 3.7 years. Cox regression models adjusted for cardiovascular risk factors and socioeconomic status, determined associations between tooth loss level (26-32 teeth: lowest level; no teeth: highest level) and cardiovascular outcomes.

    RESULTS: After adjustment, every increase in tooth loss level was associated with an increased risk of the primary outcome, the composite of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke (hazard ratio 1.06; 95% confidence interval 1.02-1.10), cardiovascular death (1.17; 1.10-1.24), all-cause death (1.16; 1.11-1.22) and non-fatal or fatal stroke (1.14; 1.04-1.24), but not with non-fatal or fatal myocardial infarction (0.99; 0.94-1.05). Having no teeth, compared to 26-32 teeth, entailed a significantly higher risk of the primary outcome (1.27 (1.08, 1.49)), cardiovascular death (1.85 (1.45, 2.37), all-cause death (1.81 (1.50, 2.20)) and stroke (1.67 (1.15, 2.39)).

    CONCLUSIONS: In this large global cohort of patients with coronary heart disease, self-reported tooth loss predicted adverse cardiovascular outcomes and all-cause death independent of cardiovascular risk factors and socioeconomic status.

12 1 - 50 of 59
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