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  • 201.
    Kumar, Jitender
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lind, Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Salihovic, Samira
    van Bavel, Bert
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Persistent Organic Pollutants and Inflammatory Markers in a Cross-Sectional Study of Elderly Swedish People: The PIVUS Cohort2014Ingår i: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 122, nr 9, s. 977-983Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Persistent organic pollutants (POPs) are compounds that are generated through various industrial activities and released in the surrounding environment. Different animal studies have shown effects of different POPs on various inflammatory markers. OBJECTIVE: Because very few studies have been conducted in humans, we assessed the associations between different POPs and inflammatory markers in a large population-based sample of elderly men and women (all 70 years of age) from Sweden. METHODS: This cross-sectional study investigated the concentrations of several polychlorinated biphenyls (PCBs), organochlorine pesticides, polychlorinated dibenzo-p-dioxin, and brominated diphenyl ether congeners and their association with a number of inflammatory markers [vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), E-selectin, C-reactive protein (CRP), total leucocyte count, tumor necrosis factor alpha (TNF-alpha), monocyte chemotactic protein 1 (MCP-1), and interleukin 6 (IL-6)] in 992 individuals. These individuals were recruited from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort. We used a total toxic equivalency (TEQ) value that measures toxicological effects with the relative potencies of various POPs. RESULTS: Following adjustment for potential confounders, the TEQ value (driven mainly by PCB-126) was significantly associated with levels of ICAM-1 (p < 10(-5)). A similar trend was also observed between sum of PCBs and VCAM-1 (p < 0.001). No significant associations were observed between levels of POPs and other inflammatory markers. CONCLUSIONS: TEQ values were associated with levels of ICAM-1, to a lesser degree also with VCAM-1, but not with CRP and several other inflammatory markers. These findings suggest an activation of vascular adhesion molecules by POPs, and particularly by PCB-126.

  • 202.
    Kumar, Jitender
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Salihovic, Samira
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    van Bavel, Bert
    Ekdahl, Kristina Nilsson
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Nilsson, Bo
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Influence of persistent organic pollutants on the complement system in a population-based human sample2014Ingår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 71, s. 94-100Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Persistent organic pollutants (POPS) are toxic compounds generated through various industrial activities and have adverse effects on human health. Studies performed in cell cultures and animals have revealed that POPs can alter immune-system functioning. The complement system is part of innate immune system that helps to clear pathogens from the body. We performed a large-scale population-based study to find out associations between summary measures of different POPs and different complement system markers. Methods: In this cross-sectional study, 16 polychlorinated biphenyls (PCBs), 3 organochlorine (OC) pesticides, octachloro-p-dibenzodioxin, and 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) were analyzed for their association with levels of protein complement 3 (C3), 3a (C3a), 4 (C4) and C3a/C3 ratio. A total of 992 individuals (all aged 70 years, 50% females) were recruited from the Prospective Investigation of the Vasculature in Uppsala Seniors cohort. Regression analysis adjusting for a variety of confounders was performed to study the associations of different POP exposures (total toxic equivalency value or TEQ and sum of 16 PCBs) with protein complements. Results: The TEQ values were found to be positively associated with C3a (beta = 0.07, 95% CI = 0.017-0.131, p = 0.01) and C3a/C3 ratio (beta = 0.07, 95% Cl = 0.015-0.126, p = 0.01) taking possible confounders into account. The association observed was mainly driven by PCB-126. Conclusion: In this study involving 992 elderly individuals from the general population, we showed that POPs, mainly PCB-126, were associated with levels of complement system markers indicating that the association of these toxic compounds with downstream disease could be mediated by activation of immune system.

  • 203.
    Kurland, Lisa
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Liljedahl, Ulrika
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Hypertension and SNP genotyping in antihypertensive treatment.2005Ingår i: Cardiovasc Toxicol, ISSN 1530-7905, Vol. 5, nr 2, s. 133-42Artikel i tidskrift (Övrigt vetenskapligt)
  • 204.
    Kurland, Lisa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Using genotyping to predict responses to anti-hypertensive treatment2005Ingår i: TIPS - Trends in Pharmacological Sciences, ISSN 0165-6147, E-ISSN 1873-3735, Vol. 26, nr 9, s. 443-7Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Hypertension is prevalent and affects approximately 1 in every 4 adults in the Western world. Although many drugs are effective in treating hypertension, an individual's response to treatment is unpredictable. Pharmacogenetics holds the promise of becoming a tool to predict this response but obstacles and shortcomings need to be overcome. Significant developments in molecular biology, including the sequencing of the genome, the cataloguing of genetic variation and the development of microarray techniques, enable analysis of many genotypes simultaneously. However, despite these technical advances there are, as yet, no clinical applications of pharmacogenetics in anti-hypertensive treatment. It is therefore necessary to design prospective pharmacogenetic studies that aim to identify a genetic profile that will predict the response to anti-hypertensive treatment.

  • 205.
    Kurland, Lisa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Karlsson, Julia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kahan, Thomas
    Malmqvist, Karin
    Öhman, K. Peter
    Nyström, Fredrik
    Hägg, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Angiotensin converting enzyme gene polymorphism predicts blood pressure response to angiotensin II receptor type 1 antagonist treatment in hypertensive patients2001Ingår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 19, nr 10, s. 1783-1787Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: To determine whether polymorphisms in the renin-angiotensin system can predict blood pressure-lowering response to antihypertensive treatment; more specifically, in response to treatment with irbesartan or atenolol. DESIGN AND METHODS: Eighty-six patients with hypertension were randomized to double-blind treatment with either the angiotensin II type 1 receptor antagonist irbesartan or the beta1 adrenergic receptor blocker atenolol and followed for 3 months. We analysed angiotensinogen T174M and M235T, angiotensin converting enzyme (ACE) I/D and angiotensin II type 1 receptor A1166C polymorphisms and related them to blood pressure reduction. RESULTS: The mean reductions in blood pressure were similar for both treatments. In the irbesartan group, individuals homozygous for the ACE gene I allele showed a greater reduction in diastolic blood pressure, exceeding those with the D allele (-18 +/- 11 SD versus -7 +/- 10 mmHg, P = 0.0096). This was not the case during treatment with atenolol, and the interaction term between type of treatment and ACE II genotype was significant (P = 0.0176). The angiotensinogen and angiotensin II type 1 receptor polymorhisms were not related to the response to treatment. CONCLUSIONS: ACE genotyping predicted the blood pressure-lowering response to antihypertensive treatment with irbesartan but not atenolol. Thus, specific genotypes might predict the response to specific antihypertensive treatment.

  • 206.
    Kurland, Lisa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Karlsson, Julia
    Kahan, Thomas
    Malmqvist, Karin
    Öhman, Peter
    Nyström, Fredrik
    Hägg, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Aldosterone synthase (CYP11B2) -344 C/T polymorphism is related to antihypertensive response: result from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial2002Ingår i: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 15, nr 5, s. 389-93Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Our aim was to determine whether the aldosterone synthase (CYP11B2) -344 C/T polymorphism was associated with the blood pressure (BP)-lowering response to antihypertensive treatment. METHODS: Patients with mild-to-moderate primary hypertension and left ventricular hypertrophy were randomized in a double-blind study to receive treatment with either the angiotensin II type 1 (AT1) receptor antagonist irbesartan (n = 43), or the beta1-adrenergic receptor blocker atenolol (n = 43). The aldosterone synthase (CYP11B2) -344 C/T polymorphism was analyzed using solid-phase minisequencing and related to BP reduction after 3 months treatment. Serum aldosterone levels were measured. RESULTS: After 3 months treatment the mean reductions in BP were similar for both treatment groups. When assessing the systolic BP reduction in the irbesartan group, patients with the TT variant had a more pronounced reduction (-21 +/- 19 SD mm Hg, n = 17) than both the TC (-14 +/- 18 mm Hg, n= 18) and CC (0 +/- 17 mm Hg, n = 8) genotypes (P = .04). There was no association between this polymorphism and the diastolic BP response. The -344 C/T polymorphism was not associated with the BP response to atenolol. Nor was it related to the baseline serum aldosterone level. CONCLUSIONS: The aldosterone synthase -344 C/T polymorphism was related to the BP-lowering response in hypertensive patients treated with the AT1-receptor antagonist irbesartan.

  • 207.
    Kurland, Lisa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Karlsson, Julia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kahan, Thomas
    Malmqvist, Karin
    Öhman, Peter
    Nyström, Fredrik
    Hägg, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Polymorphisms in the angiotensinogen and angiotensin II type 1 receptor gene are related to change in left ventricular mass during antihypertensive treatment: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial2002Ingår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 20, nr 4, s. 657-663Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Our aim was to determine if gene polymorphisms in the renin-angiotensin-aldosterone system (RAAS) were related to the degree of change in left ventricular hypertrophy (LVH) during antihypertensive treatment. METHODS AND RESULTS: Patients with essential hypertension and echocardiographically diagnosed LVH were included in a double-blind study to receive treatment with either the angiotensin II type 1 receptor (AT1-receptor) antagonist irbesartan (n = 41), or the beta-1 adrenergic receptor blocker atenolol (n = 43) as monotherapy for 3 months. The angiotensinogen T174M and M235T, the angiotensin-converting enzyme I/D, the AT1-receptor A1166C and the aldosterone synthase (CYP11B2) -344 C/T polymorphisms were analysed and related to the change in left ventricular mass (LVM). Patients with the angiotensinogen 174 TM genotype treated with irbesartan responded with the greatest reduction in LVM (-23 +/- 31SD g/m2 for TM and +0.5 +/- 18 g/m2 for TT, P = 0.005), independent of blood pressure reduction. Both the angiotensinogen 235 T-allele (P = 0.02) and the AT1-receptor 1166 AC genotype responded with the greatest reduction in LVM when treated with irbesartan (-0.1 +/- 19 g/m2 for AA and -18 +/- 30 g/m2 for AC, P = 0.02), independent of blood pressure reduction. These polymorphisms were not associated with the change in LVM during treatment with atenolol. DISCUSSION: The angiotensinogen T174M and M235T and the AT1-receptor A1166C polymorphisms were related to the change in LVH during antihypertensive treatment with an AT1-receptor antagonist; of these angiotensinogen T174M was the most powerful. This highlights the role of the RAAS for left ventricular hypertrophy and the potential of pharmacogenetics as a tool for guidance of antihypertensive therapy.

  • 208.
    La Merrill, M A
    et al.
    Department of Environmental Toxicology, University of California, Davis, CA, USA.
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Salihovic, Samira
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. MTM Research Centre, School of Science and Technology, Örebro University, Örebro, Sweden, and Norwegian Institute for Water Research, NIVA, Oslo, Norway.
    van Bavel, B
    MTM Research Centre, School of Science and Technology, Örebro University, Örebro, Sweden, and Norwegian Institute for Water Research, NIVA, Oslo, Norway.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    The association between p,p'-DDE levels and left ventricular mass is mainly mediated by obesity2018Ingår i: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 160, s. 541-546, artikel-id S0013-9351(17)31176-3Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND OBJECTIVES: The pesticide metabolite p,p'-DDE has been associated with left ventricular (LV) mass and known risk factors for LV hypertrophy in humans and in experimental models. We hypothesized that the associations of p,p'-DDE with LV hypertrophy risk factors, namely elevated glucose, adiposity and hypertension, mediate the association of p,p'-DDE with LV mass.

    METHODS: p,p'-DDE was measured in plasma from 70-year-old subjects (n = 988) of the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS). When these subjects were 70-, 75- and 80- years old, LV characteristics were measured by echocardiography, while fasting glucose, body mass index (BMI) and blood pressure were assessed with standard clinical techniques.

    RESULTS: We found that p,p'-DDE levels were associated with increased fasting glucose, BMI, hypertension and LV mass in separate models adjusted for sex. Structural equation modeling revealed that the association between p,p'-DDE and LV mass was almost entirely mediated by BMI (70%), and also by hypertension (19%).

    CONCLUSION: The obesogenic effect of p,p'-DDE is a major determinant responsible for the association of p,p'-DDE with LV mass.

  • 209.
    Lampa, Erik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Arnlöv, J.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Diabetes increases the mortality in myocardial infarction, heart failure and stroke: results from a longitudinal study over 40 years2018Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, s. S178-S178Artikel i tidskrift (Övrigt vetenskapligt)
  • 210.
    Lampa, Erik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Bornefalk Hermansson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Salihovic, Samira
    van Bavel, Bert
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    An investigation of the co-variation in circulating levels of a large number of environmental contaminants2012Ingår i: Journal of Exposure Science and Environmental Epidemiology, ISSN 1559-0631, E-ISSN 1559-064X, Vol. 22, nr 5, s. 476-482Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We are daily exposed to many different environmental contaminants. Mixtures of these contaminants could act together to induce more pronounced effects than the sum of the individual contaminants. To evaluate the effects of such mixtures, it is of importance to assess the co-variance amongst the contaminants. Thirty-seven environmental contaminants representing different classes were measured in blood samples from 1016 individuals aged 70 years. Hierarchical cluster analysis and principal component analysis were used to assess the co-variation among the contaminants. Within each identified cluster, possible marker contaminants were sought for. We validated our findings using data from the National Health and Nutrition Examination Survey (NHANES) 2003--2004 study. Two large clusters could be identified, one representing low/medium chlorinated polychlorinated biphenyls (PCBs) (<= 6 chlorine atoms), as well as two pesticides and one representing medium/high chlorinated PCBs (>= 6 chlorine atoms). PCBs 118 and 153 could be used as markers for the low/medium chlorinated cluster and PCBs 170 and 209 could be used as markers for the medium/high chlorinated cluster. This pattern was similar to data from the NHANES study. Apart from the PCBs, little co-variation was seen among the contaminants. Thus, a large number of chemicals have to be measured to adequately identify mixtures of environmental contaminants.

  • 211.
    Lampa, Erik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lind, Monica P.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Bornefalk-Hermansson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    The identification of complex interactions in epidemiology and toxicology: a simulation study of Boosted Regression Trees2014Ingår i: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 13, s. 57-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: There is a need to evaluate complex interaction effects on human health, such as those induced by mixtures of environmental contaminants. The usual approach is to formulate an additive statistical model and check for departures using product terms between the variables of interest. In this paper, we present an approach to search for interaction effects among several variables using boosted regression trees. Methods: We simulate a continuous outcome from real data on 27 environmental contaminants, some of which are correlated, and test the method's ability to uncover the simulated interactions. The simulated outcome contains one four-way interaction, one non-linear effect and one interaction between a continuous variable and a binary variable. Four scenarios reflecting different strengths of association are simulated. We illustrate the method using real data. Results: The method succeeded in identifying the true interactions in all scenarios except where the association was weakest. Some spurious interactions were also found, however. The method was also capable to identify interactions in the real data set. Conclusions: We conclude that boosted regression trees can be used to uncover complex interaction effects in epidemiological studies.

  • 212.
    Lannergård, Anders
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Friman, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Ewald, Uwe
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Serum amyloid A (SAA) protein and high-sensitivity C-reactive protein (hsCRP) in healthy newborn infants and healthy young through elderly adults2005Ingår i: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 94, nr 9, s. 1198-1202Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM:

    To determine the levels of serum amyloid A (SAA) protein and high-sensitivity C-reactive protein (hsCRP) in different age groups.

    METHODS:

    Serum samples from 70 healthy newborn infants, 80 blood donors and 81 healthy elderly individuals were analysed using a nephelometric method. The 231 samples were grouped as follows: 35 umbilical cords, 35 newborns, 48 young adults, 28 middle-aged adults, and 85 elderly adults.

    RESULTS:

    Serum levels of both SAA and hsCRP were lower in umbilical cords than in the newborns and young, middle-aged and elderly adults (p<0.0001). The SAA and hsCRP levels were comparable in newborns, and young and middle-age adults, but higher in elderly adults (p<0.0001-0.03). SAA (r2=0.159, p<0.0001) and hsCRP (r2=0.059, p<0.0001) were positively correlated with age and to each other (r2=0.385, p<0.0001).

    CONCLUSION:

    Serum levels of SAA and hsCRP in umbilical cord blood are close to the detection limit and lower than in the other age groups investigated. The elderly have generally higher levels than the younger age groups, which require higher decision levels in inflammatory diseases, including infections. In newborns and young and middle-aged adults, the lower decision levels of 10 mg/l for SAA and 5 mg/l for CRP are suggested.

  • 213.
    Larsson, Anders
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Ridefelt, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Reference intervals for parathyroid hormone for 70-year-old males and females: exclusion of individuals from the reference interval based on sex, calcium, diabetes, cardiovascular diseases or reduced kidney function has limited effects on the interval2015Ingår i: Annals of Clinical Biochemistry, ISSN 0004-5632, E-ISSN 1758-1001, Vol. 52, nr 1, s. 39-43Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: A problem when producing reference intervals for elderly individuals is that they often suffer from a number of diseases and they are most often on medication. If all such persons are excluded, there is a risk that the residual subgroup may not be representative of the population, we therefore wanted to compare the effects different exclusion criteria has on the reference intervals.

    METHODS: We measured parathyroid hormone (PTH), calcium, albumin and cystatin C in a cohort of 70-year-old males and females (n = 1003). Reference intervals for PTH for males and females were calculated for the entire population and after exclusion of persons with calcium >2.60 mmol/L, calcium >2.51 mmol/L, diabetes, reduced glomerular filtration rate (GFR), and cardiovascular diseases.

    RESULTS: The calculated PTH reference interval 16 (CI 14-17) to 94 (CI 87-101) ng/L. Exclusion of study subjects resulted in smaller reference sample groups, but the reference limits remained within the 90% confidence intervals of the original reference limits. The selections thus had a very limited effect on the calculated reference interval for PTH.

    CONCLUSIONS: Exclusion of elderly individuals with high calcium concentrations, diabetes, reduced GFR or cardiovascular disease has little effect on the reference interval for PTH. It is better not to exclude these individuals, as it will provide a broader base for the reference interval.

  • 214.
    Larsson, Anders
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Stridsberg, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk endokrinologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Reference values for fasting insulin in 75 year old females and males2013Ingår i: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 46, nr 12, s. 1125-1127Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES:

    Reference intervals for insulin are often based on fairly small study groups with unknown body mass index (BMI). They are also much younger than most patients seeking care. These values are not optimal for elderly patients, as many biological markers change over time and adequate reference intervals are important for correct clinical decisions.

    DESIGN AND METHODS:

    We studied fasting insulin (f-insulin) values in a cohort of 698 75-year old non-diabetic males and females. The 2.5th and 97.5th percentiles for all individuals, males and females were calculated according to the recommendations of the International Federation of Clinical Chemistry on the statistical treatment of reference intervals.

    RESULTS:

    There was a strong positive correlation between BMI and f-insulin, which led to the calculation of separate reference intervals for individuals with BMI ≤30.

    CONCLUSIONS:

    The reference interval for f-insulin for all study subjects was 1.74-18.27mIU/L and for individuals with BMI ≤30 (n=574) the reference interval was 1.66-15.05mIU/L.

  • 215. Lee, Duk-Hee
    et al.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Jacobs, David R., Jr.
    Salihovic, Samira
    van Bavel, Bert
    Lind, Monica P.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Does Mortality Risk of Cigarette Smoking Depend on Serum Concentrations of Persistent Organic Pollutants?: Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) Study2014Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 5, s. e95937-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cigarette smoking is an important cause of preventable death globally, but associations between smoking and mortality vary substantially across country and calendar time. Although methodological biases have been discussed, it is biologically plausible that persistent organic pollutants (POPs) like polychlorinated biphenyls (PCBs) and organochlorine (OC) pesticides can affect this association. This study was performed to evaluate if associations of cigarette smoking with mortality were modified by serum concentrations of PCBs and OC pesticides. We evaluated cigarette smoking in 111 total deaths among 986 men and women aged 70 years in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) with mean follow-up for 7.7 years. The association between cigarette smoking and total mortality depended on serum concentration of PCBs and OC pesticides (P value for interaction = 0.02). Among participants in the highest tertile of the serum POPs summary score, former and current smokers had 3.7 (95% CI, 1.5-9.3) and 6.4 (95% CI, 2.3-17.7) times higher mortality hazard, respectively, than never smokers. In contrast, the association between cigarette smoking and total mortality among participants in the lowest tertile of the serum POPs summary score was much weaker and statistically nonsignificant. The strong smoking-mortality association observed among elderly people with high POPs was mainly driven by low risk of mortality among never smokers with high POPs. As smoking is increasing in many low-income and middle-income countries and POPs contamination is a continuing problem in these areas, the interactions between these two important health-related issues should be considered in future research.

  • 216. Lee, Duk-Hee
    et al.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Jacobs, David R
    Salihovic, Samira
    van Bavel, Bert
    Lind, Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Associations of persistent organic pollutants with abdominal obesity in the elderly: The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study2012Ingår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 40, s. 170-178Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: In animal experiments, persistent organic pollutants (POPs) have induced visceral obesity. To address this possibility in humans, we evaluated associations between POPs and abdominal obesity both cross-sectionally and prospectively.

    METHODS: Twenty-one plasma POPs (16 polychlorinated biphenyl (PCB) congeners, 3 organochlorine (OC) pesticides, 1 brominated diphenyl ether (BDE), and 1 dioxin) were measured at baseline in 970 participants aged 70years of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), with prospective analyses in 511 participants re-examined after 5years. Abdominal obesity was defined by an increased waist circumference.

    RESULTS: In the cross-sectional analyses, concentrations of the less chlorinated PCBs, OC pesticides such as p,p'-DDE and dioxin had adjusted odds ratios of 2 to 3 for abdominal obesity. Many relations had inverted U-shapes rather than being linear, particularly in women. In contrast, concentrations of highly chlorinated PCBs were strongly inversely associated with abdominal obesity. In a single model including summary measures of the less chlorinated PCBs, highly chlorinated PCBs, and OC pesticides, both the positive associations and inverse associations strengthened. Similar but somewhat weaker associations were seen between POPs and risk of development of abdominal obesity in the prospective analyses.

    CONCLUSION: Using both a cross-sectional and a prospective design, low-dose exposure to less chlorinated PCBs, p,p'-DDE, and dioxin, were associated with existence or development of abdominal obesity, while highly chlorinated PCBs had an opposite association in an elderly population, despite the previous observation of higher incident diabetes associated with these same PCBs.

  • 217. Lee, Duk-Hee
    et al.
    Lind, Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Jacobs, David R
    Salihovic, Samira
    van Bavel, Bert
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Polychlorinated biphenyls and organochlorine pesticides in plasma predict development of type 2 diabetes in the elderly: the prospective investigation of the vasculature in Uppsala Seniors (PIVUS) study2011Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 34, nr 8, s. 1778-1784Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Persistent organic pollutants (POPs), lipophilic chemicals that accumulate mainly in adipose tissue, have recently been linked to type 2 diabetes. However, evidence from prospective studies is sparse. This study was performed to evaluate prospective associations of type 2 diabetes with selected POPs among the elderly.

    RESEARCH DESIGN AND METHODS: Nineteen POPs (14 polychlorinated biphenyl [PCB] congeners, 3 organochlorine pesticides, 1 brominated diphenyl ether, and 1 dioxin) were measured in plasma collected at baseline in 725 participants, aged 70 years, of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS).

    RESULTS: After adjusting for known type 2 diabetes risk factors, including obesity, odds ratios (ORs) (95% CIs) for type 2 diabetes at age 75 years (n = 36) according to the quintiles of a summary measure of concentrations of PCBs (vs. the lowest quintile) were 4.5, 5.1, 8.8 (1.8-42.7), and 7.5 (1.4-38.8) (P(trend) <0.01). Among organochlorine pesticides, adjusted ORs across concentrations of trans-nonachlor showed that P(trend) = 0.03. Adjusted ORs (95% CIs) across quintiles of the sum of three organochlorine pesticides were 1.1, 1.6, 1.5, and 3.4 (1.0-11.7) (P(trend) = 0.03). Neither brominated diphenyl ether 47 nor dioxin was significantly associated with incident diabetes. The sum of PCBs improved reclassification significantly when added to traditional risk factors for diabetes.

    CONCLUSIONS: Despite the small number of incident cases, this study found that environmental exposure to some POPs substantially increased risk of future type 2 diabetes in an elderly population.

  • 218.
    Lee, Duk-Hee
    et al.
    Kyungpook Natl Univ, Sch Med, Dept Prevent Med, Daegu, South Korea.;Kyungpook Natl Univ, Dept Biomed Sci, Plus KNU Biomed Convergence Program BK21, Daegu, South Korea..
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Jacobs, David R., Jr.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA..
    Salihovic, Samira
    Univ Orebro, Sch Sci & Technol, MTM Res Ctr, SE-70182 Orebro, Sweden..
    van Bavel, Bert
    Univ Orebro, Sch Sci & Technol, MTM Res Ctr, SE-70182 Orebro, Sweden..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Association between background exposure to organochlorine pesticides and the risk of cognitive impairment: A prospective study that accounts for weight change2016Ingår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 89-90, s. 179-184Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Background exposure to organochlorine (OC) pesticides was recently linked to cognitive impairment and dementia in cross-sectional and case-control studies. This prospective study was performed to evaluate if OC pesticides at baseline are associated with the future risk of cognitive impairment in elderly, with particular focus on weight change. Methods: Plasma concentrations of 3 OC pesticides (p,p'-DDE, trans-nonachlor, and hexachlorobenzene) were measured among 989 men and women aged 70 years in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). Cognitive impairment was validated by reviewing medical records. During the ten year follow-up, cognitive impairment was developed in 75 subjects. When weight change from age 70 to 75 was considered in analyses, elderly with incident cases before age 75 were excluded to keep the prospective perspective, leaving 795 study subjects and 44 incident cases. Results: The summary measure of 3 OC pesticides predicted the development of cognitive impairment after adjusting for covariates, including weight change. Compared to subjects with OC pesticides <25th percentile, adjusted hazard ratios (HRs) in those with 25th-<75th and >= 75th percentiles were 3.5 (95% confidence interval: 1.5-8.5) and 3.2 (1.1-7.6), respectively (P-trend = 0.04). Among 506 subjects who maintained or gained body weight, adjusted HRs were 6.9 and 11.6 (1.4-92.6) among the elderly in the 25th-<75th and >= 75th percentiles compared to <25th percentile (P-trend < 0.01). Conclusions: This prospective study demonstrates that background exposure to OC pesticides are linked to the risk of developing cognitive impairment in elderly. The role of the chronic exposure to low dose OC pesticides in the development of dementia should be further evaluated in other populations.

  • 219. Lee, Duk-Hee
    et al.
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Jacobs, David R., Jr.
    Salihovic, Samira
    van Bavel, Bert
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Background exposure to persistent organic pollutants predicts stroke in the elderly2012Ingår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 47, s. 115-120Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background exposure to persistent organic pollutants (POPs), lipophilic xenobiotics that accumulate mainly in adipose tissue, has recently emerged as a new risk factor for cardiovascular diseases. This prospective study was performed to evaluate if plasma concentrations of selected POPs predict incident stroke among the elderly. Twenty-one POPs (including 16 polychlorinated biphenyl (PCB) congeners, 3 organochlorine (OC) pesticides, 1 brominated diphenyl ether (BDE), and 1 dioxin) were measured in plasma collected at baseline in 898 participants aged 70 years of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). Stroke diagnosis was validated by hospital records. During the five year follow-up, 35 subjects developed hospital-treated stroke. After adjusting for known stroke risk factors, most PCBs with 4, 5, or 6 chlorine atoms, p,p'-DDE, trans-nonachlor, and octachlorodibenzo-p-dioxin significantly predicted the risk of stroke. Across quartiles of summary measures of PCBs and OC pesticides, the adjusted ORs were 1.0, 0.8 (95% confidence interval: 0.2-2.5), 1.2 (0.4-3.4), and 2.1 (0.7-6.2) for PCBs and 1.0, 1.2 (0.3-4.2), 2.3 (0.7-6.9), and 3.0 (1.0-9.4) for OC pesticides (P for trend = 0.11 and 0.03, respectively). The adjusted ORs among participants >= 90th percentile of the summary measures were 5.5 (1.7-18.1) for PCBs and 4.0 (1.1-14.6) for OC pesticides; corresponding ORs for those >= 95th percentile were 7.8 (2.1-29.6) and 9.5 (2.3-38.9). Background exposure to POPs may play an important role in development or progression of stroke in the elderly.

  • 220.
    Lee, Duk-Hee
    et al.
    Kyungpook Natl Univ, Sch Med, Dept Prevent Med, Daegu, South Korea.
    Porta, Miquel
    Univ Autonoma Barcelona, Sch Med, Hosp del Mar, Inst Med Res IMIM, Barcelona, Spain.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Jacobs, David R
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
    Neurotoxic chemicals in adipose tissue: A role in puzzling findings on obesity and dementia2018Ingår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 90, nr 4, s. 176-182Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Midlife obesity is associated with increased risk of dementia, whereas late-life obesity is commonly associated with a lower risk of dementia. Although methodologic issues are often discussed in this apparent risk reversal, chronic exposure to low-dose organochlorine pesticides (OCPs), an emerging risk factor for dementia in general populations, may contribute to a direct explanation for these differences. OCPs are strong lipophilic chemicals with very long half-lives (several years), primarily stored in adipose tissue and very slowly released and metabolized over years. As serum concentrations of neurotoxic OCPs strongly correlate with brain OCPs (r = 0.95), any condition enhancing the release of OCPs from the adipose tissue into circulation would increase the risk of dementia. Increased release of OCPs from adipose tissue typically occurs in (1) dysfunctional adipocytes accompanied by uncontrolled lipolysis and (2) weight loss. Weight gain may help sequester circulating OCPs in adipose tissue. As obesity is the most common reason that adipocytes become dysfunctional, midlife obesity can increase dementia risk through the chronic release of OCPs into circulation. However, late-life obesity potentially decreases dementia risk because weight loss after midlife will increase the release of OCPs while weight gain may actually decrease the release. These countervailing forces may underlie paradoxical associations with dementia of obesity in midlife vs late life which is influenced by weight change after midlife. This hypothesis should be tested in future experimental and human studies on obesity and dementia.

  • 221.
    Lejonklou, Margareta Halin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Dunder, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Bladin, Emelie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Pettersson, Vendela
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Rönn, Monika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Waldén, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Effects of Low-Dose Developmental Bisphenol A Exposure on Metabolic Parameters and Gene Expression in Male and Female Fischer 344 Rat Offspring.2017Ingår i: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 125, nr 6, artikel-id 067018Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Bisphenol A (BPA) is an endocrine-disrupting chemical that may contribute to development of obesity and metabolic disorders. Humans are constantly exposed to low concentrations of BPA, and studies support that the developmental period is particularly sensitive.

    OBJECTIVES: The aim was to investigate the effects of low-dose developmental BPA exposure on metabolic parameters in male and female Fischer 344 (F344) rat offspring.

    METHODS: Pregnant F344 rats were exposed to BPA via their drinking water, corresponding to (BPA0.5; ) or (BPA50; ), from gestational day (GD) 3.5 until postnatal day (PND) 22, and controls were given vehicle (). Body weight (BW), adipose tissue, liver (weight, histology, and gene expression), heart weight, and lipid profile were investigated in the 5-wk-old offspring.

    RESULTS: Males and females exhibited differential susceptibility to the different doses of BPA. Developmental BPA exposure increased plasma triglyceride levels ( compared with , females BPA50 ; compared with , males BPA0.5 ) in F344 rat offspring compared with controls. BPA exposure also increased adipocyte cell density by 122% in inguinal white adipose tissue (iWAT) of female offspring exposed to BPA0.5 compared with controls ( number of adipocytes/HPF compared with number of adipocytes/HPF; ) and by 123% in BPA0.5 females compared with BPA50 animals ( number of adipocytes/high power field (HPF) compared with number of adipocytes/HPF; ). In iWAT of male offspring, adipocyte cell density was increased by 129% in BPA50-exposed animals compared with BPA0.5-exposed animals ( number of adipocytes/HPF compared with number of adipocytes/HPF; ). Furthermore, the expression of genes involved in lipid and adipocyte homeostasis was significantly different between exposed animals and controls depending on the tissue, dose, and sex.

    CONCLUSIONS: Developmental exposure to of BPA, which is 8-10 times lower than the current preliminary EFSA (European Food Safety Authority) tolerable daily intake (TDI) of and is within the range of environmentally relevant levels, was associated with sex-specific differences in the expression of genes in adipose tissue plasma triglyceride levels in males and adipocyte cell density in females when F344 rat offspring of dams exposed to BPA at were compared with the offspring of unexposed controls.

  • 222.
    Li, Yan
    et al.
    Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Shanghai Inst Hypertens, Shanghai, Peoples R China.
    Thijs, Lutgarde
    Univ Leuven, Dept Cardiovasc Sci, Leuven, Belgium.
    Asayama, Kei
    Teikyo Univ, Sch Med, Dept Hyg & Publ Hlth, Tokyo, Japan.
    Hansen, Tine W.
    Res Ctr Prevent & Hlth, Copenhagen, Denmark;Steno Diabet Ctr Res Ctr Prevent & Hlth, Copenhagen, Denmark;Steno Diabet Ctr, Copenhagen, Denmark.
    Boggia, Jose
    Hosp Clin Montevideo, Dept Fisiopatol, Montevideo, Uruguay.
    Björklund-Bodegård, Kristina
    Danderyd Hosp, Dept Clin Sci, Danderyd, Sweden.
    Niiranen, Teemu J.
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.
    Ntineri, Angeliki
    Univ Athens, Hypertens Ctr, Athens, Greece.
    Zhang, Zhen-Yu
    Univ Leuven, Dept Cardiovasc Sci, Leuven, Belgium.
    Wei, Fang-Fei
    Univ Leuven, Dept Cardiovasc Sci, Leuven, Belgium.
    Yang, Wen-Yi
    Univ Leuven, Dept Cardiovasc Sci, Leuven, Belgium.
    Ohkubo, Takayoshi
    Tohoku Inst Management Blood Pressure, Sendai, Miyagi, Japan.
    Jeppesen, Jorgen
    Copenhagen Univ Hosp, Copenhagen, Denmark.
    Dolan, Eamon
    Stroke & Hypertens Unit, Dublin, Ireland.
    Hozawa, Atsushi
    Tohoku Univ, Dept Prevent Med & Epidemiol, Sendai, Miyagi, Japan.
    Tsuji, Ichiro
    Tohoku Univ, Grad Sch Med, Dept Publ Hlth, Sendai, Miyagi, Japan.
    Stolarz-Skrzypek, Katarzyna
    Jagiellonian Univ, Coll Med, Dept Cardiol & Hypertens 1, Krakow, Poland.
    Huang, Qi-Fang
    Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Shanghai Inst Hypertens, Shanghai, Peoples R China.
    Melgarejo-Arias, Jesus D.
    Univ Zulia, Lab Neurociencias, Maracaibo, Venezuela;Univ Zulia, Inst Cardiovasc, Maracaibo, Venezuela.
    Tikhonoff, Valerie
    Univ Padua, Dept Clin & Expt Med, Padua, Italy.
    Malyutina, Sofi A.
    Inst Cytol & Genet, Inst Internal & Prevent Med, Internal & Prevent Med Branch, Novosibirsk, Russia.
    Casiglia, Edoardo
    Univ Padua, Dept Clin & Expt Med, Padua, Italy.
    Nikitin, Yuri
    Inst Cytol & Genet, Inst Internal & Prevent Med, Internal & Prevent Med Branch, Novosibirsk, Russia.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Sandoya, Edgardo
    Asociac Espanola Primera Socorros Mutuos, Montevideo, Uruguay.
    Aparicio, Lucas
    Hosp Italiano Buenos Aires, Dept Med, Buenos Aires, DF, Argentina.
    Waisman, Gabriel
    Hosp Italiano Buenos Aires, Dept Med, Buenos Aires, DF, Argentina.
    Gilis-Malinowska, Natasza
    Med Univ Gdansk, Dept Hypertens, Gdansk, Poland.
    Narkiewicz, Krzysztof
    Med Univ Gdansk, Dept Hypertens, Gdansk, Poland.
    Kawecka-Jaszcz, Kalina
    Jagiellonian Univ, Coll Med, Dept Cardiol & Hypertens 1, Krakow, Poland.
    Maestre, Gladys E.
    Univ Zulia, Lab Neurociencias, Maracaibo, Venezuela;Univ Zulia, Inst Cardiovasc, Maracaibo, Venezuela.
    Jula, Antti M.
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.
    Johansson, Jouni K.
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.
    Kuznetsova, Tatiana
    Univ Leuven, Dept Cardiovasc Sci, Leuven, Belgium.
    Filipovsky, Jan
    Charles Univ Prague, Fac Med, Prague, Czech Republic.
    Stergiou, George
    Univ Athens, Hypertens Ctr, Athens, Greece.
    Wang, Ji-Guang
    Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Shanghai Inst Hypertens, Shanghai, Peoples R China.
    Imai, Yutaka
    Tohoku Inst Management Blood Pressure, Sendai, Miyagi, Japan.
    O'Brien, Eoin
    Univ Coll Dublin, Conway Inst, Dublin, Ireland.
    Staessen, Jan A.
    Univ Leuven, Dept Cardiovasc Sci, Leuven, Belgium.
    Age- sex- and ethnicity-specific prediction of cardiovascular outcomes by in-office and out-of-the-office blood pressure: a subject-level meta-analysis of 17,383 adults enrolled in 17 population studies2018Ingår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 36, s. E310-E311Artikel i tidskrift (Övrigt vetenskapligt)
  • 223. Li, Yan
    et al.
    Thijs, Lutgarde
    Boggia, Jose
    Asayama, Kei
    Hansen, Tine W.
    Kikuya, Masahiro
    Bjorklund-Bodegard, Kristina
    Ohkubo, Takayoshi
    Jeppesen, Jorgen
    Torp-Pedersen, Christian
    Dolan, Eamon
    Kuznetsova, Tatiana
    Stolarz-Skrzypek, Katarzyna
    Tikhonoff, Valerie
    Malyutina, Sofia
    Casiglia, Edoardo
    Nikitin, Yuri
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Sandoya, Edgardo
    Kawecka-Jaszcz, Kalina
    Filipovsky, Jan
    Imai, Yutaka
    Ibsen, Hans
    O'Brien, Eoin
    Wang, Jiguang
    Staessen, Jan A.
    Blood Pressure Load Does Not Add to Ambulatory Blood Pressure Level for Cardiovascular Risk Stratification2014Ingår i: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 63, nr 5, s. 925-933Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Experts proposed blood pressure (BP) load derived from 24-hour ambulatory BP recordings as a more accurate predictor of outcome than level, in particular in normotensive people. We analyzed 8711 subjects (mean age, 54.8 years; 47.0% women) randomly recruited from 10 populations. We expressed BP load as percentage (%) of systolic/diastolic readings 135/85 mm Hg and 120/70 mm Hg during day and night, respectively, or as the area under the BP curve (mm Hgxh) using the same ceiling values. During a period of 10.7 years (median), 1284 participants died and 1109 experienced a fatal or nonfatal cardiovascular end point. In multivariable-adjusted models, the risk of cardiovascular complications gradually increased across deciles of BP level and load (P<0.001), but BP load did not substantially refine risk prediction based on 24-hour systolic or diastolic BP level (generalized R-2 statistic 0.294%; net reclassification improvement 0.28%; integrated discrimination improvement 0.001%). Systolic/diastolic BP load of 40.0/42.3% or 91.8/73.6 mm Hgxh conferred a 10-year risk of a composite cardiovascular end point similar to a 24-hour systolic/diastolic BP of 130/80 mm Hg. In analyses dichotomized according to these thresholds, increased BP load did not refine risk prediction in the whole study population (R(2)0.051) or in untreated participants with 24-hour ambulatory normotension (R(2)0.034). In conclusion, BP load does not improve risk stratification based on 24-hour BP level. This also applies to subjects with normal 24-hour BP for whom BP load was proposed to be particularly useful in risk stratification.

  • 224. Li, Yan
    et al.
    Wei, Fang-Fei
    Thijs, Lutgarde
    Boggia, Jose
    Asayama, Kei
    Hansen, Tine W.
    Kikuya, Masahiro
    Bjoerklund-Bodegard, Kristina
    Ohkubo, Takayoshi
    Jeppesen, Jorgen
    Gu, Yu-Mei
    Torp-Pedersen, Christian
    Dolan, Eamon
    Liu, Yan-Ping
    Kuznetsova, Tatiana
    Stolarz-Skrzypek, Katarzyna
    Tikhonoff, Valerie
    Malyutina, Sofia
    Casiglia, Edoardo
    Nikitin, Yuri
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Sandoya, Edgardo
    Kawecka-Jaszcz, Kalina
    Mena, Luis
    Maestre, Gladys E.
    Filipovsky, Jan
    Imai, Yutaka
    O'Brien, Eoin
    Wang, Ji-Guang
    Staessen, Jan A.
    Ambulatory Hypertension Subtypes and 24-Hour Systolic and Diastolic Blood Pressure as Distinct Outcome Predictors in 8341 Untreated People Recruited From 12 Populations2014Ingår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 130, nr 6, s. 466-474Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background-Data on risk associated with 24-hour ambulatory diastolic (DBP24) versus systolic (SBP24) blood pressure are scarce. Methods and Results-We recorded 24-hour blood pressure and health outcomes in 8341 untreated people (mean age, 50.8 years; 46.6% women) randomly recruited from 12 populations. We computed hazard ratios (HRs) using multivariable-adjusted Cox regression. Over 11.2 years (median), 927 (11.1%) participants died, 356 (4.3%) from cardiovascular causes, and 744 (8.9%) experienced a fatal or nonfatal cardiovascular event. Isolated diastolic hypertension (DBP24 >= 80 mm Hg) did not increase the risk of total mortality, cardiovascular mortality, or stroke (HRs <= 1.54; P >= 0.18), but was associated with a higher risk of fatal combined with nonfatal cardiovascular, cardiac, or coronary events (HRs >= 1.75; P <= 0.0054). Isolated systolic hypertension (SBP24 >= 130 mm Hg) and mixed diastolic plus systolic hypertension were associated with increased risks of all aforementioned end points (P <= 0.0012). Below age 50, DBP24 was the main driver of risk, reaching significance for total (HR for 1-SD increase, 2.05; P=0.0039) and cardiovascular mortality (HR, 4.07; P=0.0032) and for all cardiovascular end points combined (HR, 1.74; P=0.039) with a nonsignificant contribution of SBP24 (HR <= 0.92; P >= 0.068); above age 50, SBP24 predicted all end points (HR >= 1.19; P <= 0.0002) with a nonsignificant contribution of DBP24 (0.96 <= HR <= 1.14; P >= 0.10). The interactions of age with SBP24 and DBP24 were significant for all cardiovascular and coronary events (P <= 0.043). Conclusions-The risks conferred by DBP24 and SBP24 are age dependent. DBP24 and isolated diastolic hypertension drive coronary complications below age 50, whereas above age 50 SBP24 and isolated systolic and mixed hypertension are the predominant risk factors.

  • 225.
    Liao, Ximing
    et al.
    Goethe Univ Frankfurt, Dept Neurol, Frankfurt, Germany..
    Norata, Giuseppe D.
    Univ Milan, Dipartimento Sci Farmacol & Biomol, I-20122 Milan, Italy.;Bassini Hosp, SISA Ctr Study Atherosclerosis, Cinisello Balsamo, Italy..
    Polak, Joseph F.
    Tufts Univ, Sch Med, Tufts Med Ctr, Boston, MA 02111 USA..
    Stehouwer, Coen D. A.
    Maastricht Univ, Dept Internal Med, Med Ctr, NL-6200 MD Maastricht, Netherlands.;Maastricht Univ, Cardiovasc Res Inst Maastricht CARIM, Med Ctr, NL-6200 MD Maastricht, Netherlands..
    Catapano, Alberico
    IRCSS Multimed, Milan, Italy.;Univ Milan, Dept Pharmacol & Biomol Sci, I-20122 Milan, Italy..
    Rundek, Tatjana
    Univ Miami, Miller Sch Med, Dept Neurol, Coral Gables, FL 33124 USA..
    Ezhov, Marat
    Cardiol Res Ctr, Atherosclerosis Dept, Moscow, Russia..
    Sander, Dirk
    Benedictus Hosp Tutzing & Feldafing, Dept Neurol, Feldafing, Germany.;Tech Univ Munich, Dept Neurol, D-80290 Munich, Germany..
    Thompson, Simon G.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Sch Clin Med, Cambridge CB2 1TN, England..
    Lorenz, Matthias W.
    Goethe Univ Frankfurt, Dept Neurol, Frankfurt, Germany..
    Balakhonova, Tatyana
    Cardiol Res Ctr 2, Ultrasound Vasc Lab, Moscow, Russia..
    Safarova, Maya
    Cardiol Res Ctr, Atherosclerosis Dept, Moscow, Russia..
    Grigore, Liliana
    Bassini Hosp, SISA Ctr Study Atherosclerosis, Cinisello Balsamo, Italy..
    Empana, Jean-Philippe
    Univ Paris 05, Sorbonne Paris Cite, Paris Cardiovasc Res Ctr PARCC, Paris, France..
    Lin, Hung-Ju
    Natl Taiwan Univ Hosp, Dept Internal Med, Taipei, Taiwan..
    McLachlan, Stela
    Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9YL, Midlothian, Scotland..
    Bokemark, Lena
    Gothenburg Univ, Wallenberg Lab Cardiovasc Res, Inst Medicin, Dept Mol & Clin Med,Sahlgrenska Acad, S-41124 Gothenburg, Sweden..
    Ronkainen, Kimmo
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland..
    Schminke, Ulf
    Greifswald Univ Clin, Dept Neurol, Greifswald, Germany..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Uppsala Univ, Dept Med, Uppsala, Sweden..
    Willeit, Peter
    Univ Cambridge, Dept Publ Hlth & Primary Care, Sch Clin Med, Cambridge CB2 1TN, England.;Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria..
    Yanez, David N.
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA..
    Steinmetz, Helmuth
    Goethe Univ Frankfurt, Dept Neurol, Frankfurt, Germany..
    Poppert, Holger
    Tech Univ Munich, Dept Neurol, D-80290 Munich, Germany..
    Desvarieux, Moise
    Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA..
    Ikram, M. Arfan
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus Univ, Med Ctr, Dept Neurol, Rotterdam, Netherlands.;Erasmus Univ, Med Ctr, Dept Radiol, Rotterdam, Netherlands..
    Johnsen, Stein Harald
    Univ Tromso, Dept Clin Med, N-9001 Tromso, Norway.;Univ Hosp Northern Norway, Dept Neurol, Tromso, Norway..
    Iglseder, Bernhard
    Parcelsus Med Univ, Salzburg, Austria.;Gemeinnutzige Salzburger Landeskliniken Betriebse, Christian Doppler Klin, Dept Geriatr Med, Salzburg, Austria..
    Friera, Alfonsa
    Univ Autonoma Madrid, Dept Radiol, Hosp Univ Princesa, E-28049 Madrid, Spain..
    Xie, Wuxiang
    Capital Med Univ, Dept Epidemiol, Beijing Inst Heart Lung & Blood Vessel Dis, Beijing Anzhen Hosp, Beijing, Peoples R China..
    Plichart, Matthieu
    Hop Broca, AP HP, Paris, France..
    Su, Ta-Chen
    Natl Taiwan Univ Hosp, Dept Internal Med, Taipei, Taiwan..
    Srinivasan, Sathanur R.
    Tulane Univ, Sch Publ Hlth & Trop Med, Ctr Cardiovasc Hlth, Dept Epidemiol,Biochem, New Orleans, LA USA..
    Schmidt, Caroline
    Gothenburg Univ, Wallenberg Lab Cardiovasc Res, Inst Medicin, Dept Mol & Clin Med,Sahlgrenska Acad, S-41124 Gothenburg, Sweden..
    Tuomainen, Tomi-Pekka
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland..
    Volzke, Henry
    SHIP Clin Epidemiol Res, Inst Community Med, Greifswald, Germany..
    Nijpels, Giel
    Vrije Univ Amsterdam, Med Ctr, Dept Gen Practice, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands.;Univ Autonoma Madrid, Dept Internal Med, Hosp Univ Princesa, E-28049 Madrid, Spain..
    Willeit, Johann
    Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria..
    Franco, Oscar H.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Suarez, Carmen
    Zhao, Dong
    Capital Med Univ, Dept Epidemiol, Beijing Inst Heart Lung & Blood Vessel Dis, Beijing Anzhen Hosp, Beijing, Peoples R China..
    Ducimetiere, Pierre
    Univ Paris 11, Le Kremlin Bicetre, France..
    Chien, Kuo-Liong
    Natl Taiwan Univ, Inst Epidemiol & Prevent Med, Coll Publ Hlth, Taipei, Taiwan..
    Robertson, Christine
    Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9YL, Midlothian, Scotland..
    Bergstrom, Goran
    Gothenburg Univ, Wallenberg Lab Cardiovasc Res, Inst Medicin, Dept Mol & Clin Med,Sahlgrenska Acad, S-41124 Gothenburg, Sweden..
    Kauhanen, Jussi
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland..
    Dorr, Marcus
    Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany.;Partner Site Greifswald, German Ctr Cardiovasc Res DZHK, Greifswald, Germany..
    Dekker, Jaqueline M.
    Univ Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands..
    Kiechl, Stefan
    Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria..
    Sitzer, Matthias
    Goethe Univ Frankfurt, Dept Neurol, Frankfurt, Germany.;Klinikum Herford, Dept Neurol, Herford, Germany..
    Bickel, Horst
    Tech Univ Munich, Dept Psychiat & Psychotherapy, D-80290 Munich, Germany..
    Sacco, Ralph L.
    Univ Miami, Miller Sch Med, Dept Neurol, Coral Gables, FL 33124 USA..
    Hofman, Albert
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Mathiesen, Ellisiv B.
    Univ Tromso, Dept Clin Med, N-9001 Tromso, Norway.;Univ Hosp Northern Norway, Dept Neurol, Tromso, Norway..
    Gabriel, Rafael
    Hosp Univ La Paz, Inst Invest IdiPAZ, Madrid, Spain..
    Liu, Jing
    Capital Med Univ, Dept Epidemiol, Beijing Inst Heart Lung & Blood Vessel Dis, Beijing Anzhen Hosp, Beijing, Peoples R China..
    Berenson, Gerald
    Tulane Univ, Sch Med, Dept Med, Pediat,Biochem,Epidemiol, 1430 Tulane Ave, New Orleans, LA 70112 USA.;Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA USA..
    Kavousi, Maryam
    Erasmus MC, Dept Epidemiol & Biostat, Rotterdam, Netherlands..
    Price, Jackie F.
    Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9YL, Midlothian, Scotland..
    Normative values for carotid intima media thickness and its progression: Are they transferrable outside of their cohort of origin?2016Ingår i: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 23, nr 11, s. 1165-1173Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background The clinical use of carotid intima media thickness (cIMT) requires normal values, which may be subject to variation of geographical factors, ethnicity or measurement details. The influence of these factors has rarely been studied. The aim of this study was to determine whether normative cIMT values and their association with event risk are generalizable across populations. Design Meta-analysis of individual participant data. Method From 22 general population cohorts from Europe, North America and Asia we selected subjects free of cardiovascular disease. Percentiles of cIMT and cIMT progression were assessed separately for every cohort. Cox proportional hazards models for vascular events were used to estimate hazard ratios for cIMT in each cohort. The estimates were pooled across Europe, North America and Asia, with random effects meta-analysis. The influence of geography, ethnicity and ultrasound protocols on cIMT values and on the hazard ratios was examined by meta-regression. Results Geographical factors, ethnicity and the ultrasound protocol had influence neither on the percentiles of cIMT and its progression, nor on the hazard ratios of cIMT for vascular events. Heterogeneity for percentiles of cIMT and cIMT progression was too large to create meaningful normative values. Conclusions The distribution of cIMT values is too heterogeneous to define universal or regional population reference values. CIMT values vary widely between different studies regardless of ethnicity, geographic location and ultrasound protocol. Prediction of vascular events with cIMT values was more consistent across all cohorts, ethnicities and regions.

  • 226. Ligthart, Symen
    et al.
    Vaez, Ahmad
    Võsa, Urmo
    Stathopoulou, Maria G
    de Vries, Paul S
    Prins, Bram P
    Van der Most, Peter J
    Tanaka, Toshiko
    Naderi, Elnaz
    Rose, Lynda M
    Wu, Ying
    Karlsson, Robert
    Barbalic, Maja
    Lin, Honghuang
    Pool, René
    Zhu, Gu
    Macé, Aurélien
    Sidore, Carlo
    Trompet, Stella
    Mangino, Massimo
    Sabater-Lleal, Maria
    Kemp, John P
    Abbasi, Ali
    Kacprowski, Tim
    Verweij, Niek
    Smith, Albert V
    Huang, Tao
    Marzi, Carola
    Feitosa, Mary F
    Lohman, Kurt K
    Kleber, Marcus E
    Milaneschi, Yuri
    Mueller, Christian
    Huq, Mahmudul
    Vlachopoulou, Efthymia
    Lyytikäinen, Leo-Pekka
    Oldmeadow, Christopher
    Deelen, Joris
    Perola, Markus
    Zhao, Jing Hua
    Feenstra, Bjarke
    Amini, Marzyeh
    Lahti, Jari
    Schraut, Katharina E
    Fornage, Myriam
    Suktitipat, Bhoom
    Chen, Wei-Min
    Li, Xiaohui
    Nutile, Teresa
    Malerba, Giovanni
    Luan, Jian'an
    Bak, Tom
    Schork, Nicholas
    Del Greco M, Fabiola
    Thiering, Elisabeth
    Mahajan, Anubha
    Marioni, Riccardo E
    Mihailov, Evelin
    Eriksson, Joel
    Ozel, Ayse Bilge
    Zhang, Weihua
    Nethander, Maria
    Cheng, Yu-Ching
    Aslibekyan, Stella
    Ang, Wei
    Gandin, Ilaria
    Yengo, Loïc
    Portas, Laura
    Kooperberg, Charles
    Hofer, Edith
    Rajan, Kumar B
    Schurmann, Claudia
    den Hollander, Wouter
    Ahluwalia, Tarunveer S
    Zhao, Jing
    Draisma, Harmen H M
    Ford, Ian
    Timpson, Nicholas
    Teumer, Alexander
    Huang, Hongyan
    Wahl, Simone
    Liu, YongMei
    Huang, Jie
    Uh, Hae-Won
    Geller, Frank
    Joshi, Peter K
    Yanek, Lisa R
    Trabetti, Elisabetta
    Lehne, Benjamin
    Vozzi, Diego
    Verbanck, Marie
    Biino, Ginevra
    Saba, Yasaman
    Meulenbelt, Ingrid
    O'Connell, Jeff R
    Laakso, Markku
    Giulianini, Franco
    Magnusson, Patrik K E
    Ballantyne, Christie M
    Hottenga, Jouke Jan
    Montgomery, Grant W
    Rivadineira, Fernando
    Rueedi, Rico
    Steri, Maristella
    Herzig, Karl-Heinz
    Stott, David J
    Menni, Cristina
    Frånberg, Mattias
    St Pourcain, Beate
    Felix, Stephan B
    Pers, Tune H
    Bakker, Stephan J L
    Kraft, Peter
    Peters, Annette
    Vaidya, Dhananjay
    Delgado, Graciela
    Smit, Johannes H
    Großmann, Vera
    Sinisalo, Juha
    Seppälä, Ilkka
    Williams, Stephen R
    Holliday, Elizabeth G
    Moed, Matthijs
    Langenberg, Claudia
    Räikkönen, Katri
    Ding, Jingzhong
    Campbell, Harry
    Sale, Michele M
    Chen, Yii-Der I
    James, Alan L
    Ruggiero, Daniela
    Soranzo, Nicole
    Hartman, Catharina A
    Smith, Erin N
    Berenson, Gerald S
    Fuchsberger, Christian
    Hernandez, Dena
    Tiesler, Carla M T
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Liewald, David
    Fischer, Krista
    Mellström, Dan
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Wang, Yunmei
    Scott, William R
    Lorentzon, Matthias
    Beilby, John
    Ryan, Kathleen A
    Pennell, Craig E
    Vuckovic, Dragana
    Balkau, Beverly
    Concas, Maria Pina
    Schmidt, Reinhold
    Mendes de Leon, Carlos F
    Bottinger, Erwin P
    Kloppenburg, Margreet
    Paternoster, Lavinia
    Boehnke, Michael
    Musk, A W
    Willemsen, Gonneke
    Evans, David M
    Madden, Pamela A F
    Kähönen, Mika
    Kutalik, Zoltán
    Zoledziewska, Magdalena
    Karhunen, Ville
    Kritchevsky, Stephen B
    Sattar, Naveed
    Lachance, Genevieve
    Clarke, Robert
    Harris, Tamara B
    Raitakari, Olli T
    Attia, John R
    van Heemst, Diana
    Kajantie, Eero
    Sorice, Rossella
    Gambaro, Giovanni
    Scott, Robert A
    Hicks, Andrew A
    Ferrucci, Luigi
    Standl, Marie
    Lindgren, Cecilia M
    Starr, John M
    Karlsson, Magnus
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Li, Jun Z
    Chambers, John C
    Mori, Trevor A
    de Geus, Eco J C N
    Heath, Andrew C
    Martin, Nicholas G
    Auvinen, Juha
    Buckley, Brendan M
    de Craen, Anton J M
    Waldenberger, Melanie
    Strauch, Konstantin
    Meitinger, Thomas
    Scott, Rodney J
    McEvoy, Mark
    Beekman, Marian
    Bombieri, Cristina
    Ridker, Paul M
    Mohlke, Karen L
    Pedersen, Nancy L
    Morrison, Alanna C
    Boomsma, Dorret I
    Whitfield, John B
    Strachan, David P
    Hofman, Albert
    Vollenweider, Peter
    Cucca, Francesco
    Jarvelin, Marjo-Riitta
    Jukema, J Wouter
    Spector, Tim D
    Hamsten, Anders
    Zeller, Tanja
    Uitterlinden, André G
    Nauck, Matthias
    Gudnason, Vilmundur
    Qi, Lu
    Grallert, Harald
    Borecki, Ingrid B
    Rotter, Jerome I
    März, Winfried
    Wild, Philipp S
    Lokki, Marja-Liisa
    Boyle, Michael
    Salomaa, Veikko
    Melbye, Mads
    Eriksson, Johan G
    Wilson, James F
    Penninx, Brenda W J H
    Becker, Diane M
    Worrall, Bradford B
    Gibson, Greg
    Krauss, Ronald M
    Ciullo, Marina
    Zaza, Gianluigi
    Wareham, Nicholas J
    Oldehinkel, Albertine J
    Palmer, Lyle J
    Murray, Sarah S
    Pramstaller, Peter P
    Bandinelli, Stefania
    Heinrich, Joachim
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA USA; Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA USA.
    Deary, Ian J
    Mägi, Reedik
    Vandenput, Liesbeth
    van der Harst, Pim
    Desch, Karl C
    Kooner, Jaspal S
    Ohlsson, Claes
    Hayward, Caroline
    Lehtimäki, Terho
    Shuldiner, Alan R
    Arnett, Donna K
    Beilin, Lawrence J
    Robino, Antonietta
    Froguel, Philippe
    Pirastu, Mario
    Jess, Tine
    Koenig, Wolfgang
    Loos, Ruth J F
    Evans, Denis A
    Schmidt, Helena
    Smith, George Davey
    Slagboom, P Eline
    Eiriksdottir, Gudny
    Morris, Andrew P
    Psaty, Bruce M
    Tracy, Russell P
    Nolte, Ilja M
    Boerwinkle, Eric
    Visvikis-Siest, Sophie
    Reiner, Alex P
    Gross, Myron
    Bis, Joshua C
    Franke, Lude
    Franco, Oscar H
    Benjamin, Emelia J
    Chasman, Daniel I
    Dupuis, Josée
    Snieder, Harold
    Dehghan, Abbas
    Alizadeh, Behrooz Z
    Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders2018Ingår i: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 103, nr 5, s. 691-706, artikel-id S0002-9297(18)30320-3Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 10-8). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences.

  • 227.
    Liljedahl, Ulrika
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kahan, Thomas
    Malmqvist, Karin
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kurland, Lisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Single nucleotide polymorphisms predict the change in left ventricular mass in response to antihypertensive treatment2004Ingår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 22, nr 12, s. 2321-8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Our aim was to determine whether the change in left ventricular (LV) mass in response to antihypertensive treatment could be predicted by multivariate analysis of single nucleotide polymorphisms (SNPs) in candidate genes reflecting pathways likely to be involved in blood pressure control. METHODS: Patients with mild to moderate primary hypertension and LV hypertrophy were randomized in a double-blind fashion to treatment with either the angiotensin II type 1 receptor antagonist irbesartan (n = 48) or the beta1 adrenoreceptor blocker atenolol (n = 49). A microarray-based minisequencing system was used for genotyping 74 SNPs in 25 genes. These genotypes were related to the change in LV mass index by echocardiography, after 12 weeks treatment as monotherapy, using stepwise multiple regression analysis. RESULTS: The blood pressure reductions were similar and significant in both treatment groups. Two SNPs in two separate genes (the angiotensinogen T1198C polymorphism, corresponding to the M235T variant and the apolipoprotein B G10108A polymorphism) for those treated with irbesartan, and the adrenoreceptor alpha2A A1817G for those treated with atenolol, significantly predicted the change in LV mass. The predictive power of these SNPs was independent of the degree of blood pressure reduction. CONCLUSION: SNPs in the angiotensinogen, apolipoprotein B, and the alpha2 adrenoreceptor gene predicted the change in LV mass during antihypertensive therapy. These results illustrate the potential of using microarray-based technology for SNP genotyping in predicting individual drug responses.

  • 228.
    Liljedahl, Ulrika
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Karlsson, Julia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kurland, Lisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lindersson, Marie
    Kahan, Thomas
    Nyström, Fredrik
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    A microarray minisequencing system for pharmacogenetic profiling of antihypertensive drug response2003Ingår i: Pharmacogenetics, ISSN 0960-314X, E-ISSN 1473-561X, Vol. 13, nr 1, s. 7-17Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We aimed to develop a microarray genotyping system for multiplex analysis of a panel of single nucleotide polymorphisms (SNPs) in genes encoding proteins involved in blood pressure regulation, and to apply this system in a pilot study demonstrating its feasibility in the pharmacogenetics of hypertension. A panel of 74 SNPs in 25 genes involved in blood pressure regulation was selected from the SNP databases, and genotyped in DNA samples of 97 hypertensive patients. The patients had been randomized to double-blind treatment with either the angiotensin II type 1 receptor blocker irbesartan or the beta 1-adrenergic receptor blocker atenolol. Genotyping was performed using a microarray based DNA polymerase assisted 'minisequencing' single nucleotide primer extension assay with fluorescence detection. The observed genotypes were related to the blood pressure reduction using stepwise multiple regression analysis. The allele frequencies of the selected SNPs were determined in the Swedish population. The established microarray-based genotyping system was validated and allowed unequivocal multiplex genotyping of the panel of 74 SNPs in every patient. Almost 7200 SNP genotypes were generated in the study. Profiles of four or five SNP-genotypes that may be useful as predictors of blood pressure reduction after antihypertensive treatment were identified. Our results highlight the potential of microarray-based technology for SNP genotyping in pharmacogenetics.

  • 229. Liljedahl, Ulrika
    et al.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kurland, Lisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Berglund, Lars
    Kahan, Thomas
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Single nucleotide polymorphisms in the apolipoprotein B and low density lipoprotein receptor genes affect response to antihypertensive treatment2004Ingår i: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 4, nr 1, s. 16-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Dyslipidemia has been associated with hypertension. The present study explored if polymorphisms in genes encoding proteins in lipid metabolism could be used as predictors for the individual response to antihypertensive treatment. METHODS: Ten single nucleotide polymorphisms (SNP) in genes related to lipid metabolism were analysed by a microarray based minisequencing system in DNA samples from ninety-seven hypertensive subjects randomised to treatment with either 150 mg of the angiotensin II type 1 receptor blocker irbesartan or 50 mg of the beta1-adrenergic receptor blocker atenolol for twelve weeks. RESULTS: The reduction in blood pressure was similar in both treatment groups. The SNP C711T in the apolipoprotein B gene was associated with the blood pressure response to irbesartan with an average reduction of 19 mmHg in the individuals carrying the C-allele, but not to atenolol. The C16730T polymorphism in the low density lipoprotein receptor gene predicted the change in systolic blood pressure in the atenolol group with an average reduction of 14 mmHg in the individuals carrying the C-allele. CONCLUSIONS: Polymorphisms in genes encoding proteins in the lipid metabolism are associated with the response to antihypertensive treatment in a drug specific pattern. These results highlight the potential use of pharmacogenetics as a guide for individualised antihypertensive treatment, and also the role of lipids in blood pressure control.

  • 230.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    A combined test of acetylcholine-mediated vasodilation of both the forearm resistance vessels and the radial artery2013Ingår i: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 33, nr 3, s. 206-210Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective To evaluate a new combined test of endothelium-dependent vasodilation (EDV) in the forearm resistance vessel and the radial artery. Methods Acetylcholine (ACh) and sodium nitroprusside (SNP) infusion in the brachial artery were used to simultaneous evaluate EDV and endothelium-independent vasodilation (EIDV) in forearm resistance vessels (plethysmography) and in the radial artery (ultrasound) in 76 healthy subjects. Brachial artery ultrasound was used to assess flow-mediated vasodilation (FMD). Results Acetylcholine induced a 4 center dot 5% (median value, P=0 center dot 0010) increase in the radial artery diameter, while SNP induced a 31 center dot 2% increase in diameter (P<0 center dot 0001). While no increase in radial artery blood flow was induced by ACh (P=0 center dot 69), an increase by 181% in radial blood flow was induced by SNP (P<0 center dot 0001). When relating the radial artery diameter data to FMD, the change in radial artery diameter induced by ACh was significantly correlated with FMD (r=0 center dot 35, P=0 center dot 013). No such relationship was seen for the diameter change induced by SNP (r=0 center dot 03, P=0 center dot 81). When relating the radial artery blood flow data to EDV and EIDV, the change in radial artery blood flow induced by ACh was significantly correlated with EDV in an inverse fashion (r=0 center dot 42, P=0 center dot 0032). No such relationship was seen for the blood flow change induced by SNP when related to EIDV (r=0 center dot 07, P=0 center dot 63). Conclusion Simultaneous measurements of blood flow in forearm vessels by plethysmography and in the radial artery by ultrasound during ACh infusion is a new way to assess EDV in both resistance and conduit arteries during one investigation.

  • 231.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    A detailed lipoprotein profile in relation to intima-media thickness and echogenicity of three major arteries2019Ingår i: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 39, nr 6, s. 415-421Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective

    To investigate differences in risk‐factor profile, with special emphasis on detailed characterization of the lipoprotein profile, for intima‐media thickness (IMT) and echogenicity of the intima‐media complex (IM‐GSM) in three major arteries: the carotid, femoral and brachial arteries.

    Methods

    IMT and IM‐GSM were measured by ultrasound in the carotid, femoral and brachial arteries in 778 subjects, all aged 75 years (50% women), in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, in which a detailed lipoprotein profile was also determined by nuclear magnetic resonance spectroscopy.

    Results

    First, IMT was considerably lower, and IM‐GSM higher, in the brachial artery compared to the other two arteries. Second, IMT and IM‐GSM in the arteries were related to each other. Third, significant different traditional risk‐factor profiles were seen for both IMT and IM‐GSM, with generally weaker relationships for IMT in the femoral and brachial arteries compared with the carotid artery. Fourth, the strength of associations between an atherogenic lipoprotein profile and IMT in the carotid artery was attenuated in the femoral artery and virtually absent in the brachial artery. Fifth, slightly different lipoprotein profiles were seen for IM‐GSM in the three arteries.

    Conclusion

    Differences between the carotid, femoral and brachial artery IMT and IM‐GSM were seen regarding the traditional risk factors, as well as the lipoprotein profile.

  • 232.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Arterial compliance influences the measurement of flow-mediated vasodilation, but not acetylcholine-mediated forearm blood flow. The prospective investigation of the vasculature in uppsala seniors (PIVUS) study2007Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 190, nr 1, s. 212-215Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: Flow-mediated vasodilation (FMD) is low even in healthy elderly and therefore relations between FMD and cardiovascular risk factors might be hard to evaluate in the elderly. Using data from the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, we investigated if a reduced arterial distensibility could influence FMD measurements. Methods: In the population-based PIVUS study (1016 subjects aged 70), assessments of arterial distensibility by ultrasound in the carotid artery (CCA) and FMD were performed. Endothelium-dependent vasodilation was also evaluated with the invasive forearm technique with acetylcholine (EDV) and by pulse wave analysis following terbutaline injection. A poor CCA distensibility was defined as <25th percentile in the healthy part of the population (n = 131). Results: FMD was significantly related to the Framingham risk score only in those with a good CCA distensibility (r = -0.16, p = 0.0081 versus r = -0.06, p = 0.17 in those with a poor CCA distensibility, p = 0.0001 for difference). In contrast, the relationship between EDV and coronary risk was not affected by CCA distensibility (r = -0.11, p = 0.018 versus r = -0.13, p = 0.027). Conclusions: A reduced CCA distensibility could in part explain the low FMD values in the elderly. FMD correlated to the Framingham risk score only in those with a good CCA distensibility, exemplifying a limitation of the use of FMD in elderly populations. On the contrary, EDV was not affected by arterial stiffness.

  • 233.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Comment on JIM-16-0640.R1. "Mortality from aortic stenosis - prospective study of serum calcium and phosphate' by D. Wald2017Ingår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 281, nr 4, s. 412-413Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    .

  • 234.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Endothelium-dependent vasodilation predicts the development of the metabolic syndrome2015Ingår i: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 35, nr 6, s. 411-417Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Different techniques to evaluate endothelium-dependent vasodilation (EDV) in resistance and conduit arteries have been described and have been associated with the occurrence of the metabolic syndrome (MetS) in cross-sectional studies. This study aimed to evaluate whether EDV in resistance and conduit arteries could predict future development of the MetS in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study. Methods: In the population-based PIVUS study (1016 subjects all aged 70 at baseline), the invasive forearm technique with acetylcholine given in the brachial artery (resistance arteries, EDV) and the brachial artery ultrasound technique with the measurement of flow-mediated dilatation (conduit artery, FMD) were evaluated. Six hundred and twenty-four subjects free of the MetS (NCEP/ATPIII criteria) at the age of 70 were reinvestigated at the age of 75. Results: During the 5-year follow-up, 109 new subjects developed the MetS. EDV, but not FMD, predicted the development of the MetS (OR 0.78 for a 1 SD increase in EDV, 95% CI 0.62-0.97, P = 0.033). Of the five components of the MetS, EDV could significantly predict the development of the glucose (P = 0.02), waist circumference (P = 0.01) and the triglyceride components (P = 0.002), but not significantly so the HDL (P = 0.09) and blood pressure components (P = 0.92). Conclusions: EDV in resistance arteries, but not in the brachial conduit artery (FMD), was a predictor of future development of the MetS, mainly by prediction of future impairments in fasting glucose, serum triglycerides and waist circumference in an elderly cohort.

  • 235.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Flow-mediated vasodilation over five years in the general elderly population and its relation to cardiovascular risk factors2014Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 237, nr 2, s. 666-670Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Flow-mediated vasodilation (FMD) has previously been shown to be related to cardiovascular risk factors in cross-sectional studies. The present study aims to investigate how FMD changes over time, and determine whether this change is paralleled by changes in cardiovascular risk factors. Methods: Of the participants in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, 750 individuals had measurements made of FMD in the brachial artery both at the ages of 70 and 75 years. In addition, the change over the 5 years in carotid artery intima-media thickness (IMT) was monitored, as well as traditional cardiovascular risk factors. Results: While no significant change in FMD occurred during the 5-year period (+0.1%, p = 0.53), large changes could be seen at the individual level. The Framingham risk score (excluding the age-variable) increased during the follow-up period (+0.54, p < 0.001). This change was inversely related to the individual change in FMD (beta -0.15, 95% CI -0.29 to 0.0059, p = 0.041). Of the eight individual CV risk factors tested, the change in FMD was only related to the change in LDL-cholesterol (inversely, p = 0.0028). The change in FMD was not related to the change in IMT seen over the 5-year period (p = 0.41). Conclusion: While no change was seen in the mean FMD over a five-year period in elderly subjects attending both examinations despite ageing and a change in several risk factors, the individual change was mainly related to the change in LDL-cholesterol, further emphasizing the important role of lipids to determine vasoreactivity.

  • 236.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Flow-Mediated Vasodilation was Found to be an Independent Predictor of Changes in the Carotid Plaque Status During a 5-Year Follow-Up: A Prospective Investigation of the Vasculature in the Uppsala Seniors (PIVUS) Study2014Ingår i: Journal of Atherosclerosis and Thrombosis, ISSN 1880-3873, E-ISSN 1340-3478, Vol. 21, nr 2, s. 161-168Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim: It has previously been shown that flow-mediated vasodilation is a predictor of the progression of the intima-media thickness (IMT). In the present study, the degree of endothelium-dependent vasodilation in both resistance and conduit arteries was evaluated as a predictor of the IMT and plaque progression. Methods: In the population-based Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) trial (1,016 subjects all 70 years of age), the invasive forearm technique using acetylcholine administered in the brachial artery (resistance artery, EDV) and the brachial artery ultrasound technique with measurement of flow-mediated dilatation (conduit artery, FMD) were evaluated. The IMT and number of carotid arteries with plaques (0, 1 or 2) were recorded using ultrasound at the baseline investigation and the follow-up visit conducted five years later. Results: A total of 760 subjects had valid measurements of the IMT and carotid artery plaques at both the investigations conducted at 70 and 75 years of age. Neither the FMD nor EDV significantly predicted the change in IMT over five years. However, the FMD, but not EDV, was associated with the change in carotid plaque burden during the follow-up period, independent of classical risk factors, such as gender, waist circumference, fasting blood glucose, systolic and diastolic blood pressure, HDL- and LDL-cholesterol, serum triglycerides, BMI and smoking (OR 0.81 for a 1 SD change in FMD, 95% CI 0.68 to 0.95, p=0.010). Conclusions: The FMD was found to be a predictor of changes in the carotid plaque status, but not IMT, during the 5-year follow-up period, independent of classical cardiovascular risk factors.

  • 237.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Population-based cardiovascular cohort studies in Uppsala2019Ingår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, nr 1, s. 16-20Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The first population-based cohort study in Uppsala with the aim to study cardiovascular disease was initiated in 1970 (ULSAM). This cohort of 2300 middle-aged men has since then been followed in a longitudinal fashion for almost 50 years. This study has been followed by the PIVUS study, investigating 1000 men and women at ages 70, 75, and 80. A very detailed examination has also been performed in 500 subjects aged 50 years, the POEM study. In recent years, a high-throughput study conducted in 13000 subjects has also been performed, named EpiHealth. Uppsala also collects data in 5,000 subjects in the nationwide SCAPIS study. Taken together, these cardiovascular-oriented studies constitute a very rich source for cardiovascular epidemiological research in Uppsala. This review summarizes the design of these studies and highlights some of the important results published based on data from these studies.

  • 238.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ranking of cardiovascular impairments in impaired glucose tolerance2018Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, s. S576-S576Artikel i tidskrift (Övrigt vetenskapligt)
  • 239.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Relationships between three different tests to evaluate endothelium-dependent vasodilation and cardiovascular risk in a middle-aged sample2013Ingår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 31, nr 8, s. 1570-1574Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective:

    For a couple of decades, flow-mediated vasodilation in the brachial artery (FMD) and acetylcholine-mediated vasodilation in the forearm (EDV) have been used to assess endothelium-dependent vasodilation. During recent years a third technique, peripheral artery tonometry (PAT) using EndoPat, has been introduced. We now aimed to investigate the relationships between these techniques, and their relation to cardiovascular risk.

    Methods:

    In the population-based Prospective investigation of Obesity, Energy and Metabolism (POEM) study conducted in individuals all aged 50 years (50% women), EDV, FMD and the reactive hyperemia index were measured in the first 222 individuals. Cardiovascular risk was assessed by the Framingham risk score.

    Results:

    No significant relationships were seen between the three different tests to evaluate endothelium-dependent vasodilation. EDV (r=-0.21, P=0.004) and FMD (r=-0.19, P=0.004), but not PAT were significantly related to the Framingham score in an inverse way. Also sodium nitroprusside-mediated vasodilation in the forearm, reflecting endothelium-independent vasodilation (EIDV), was related to the Framingham score in an inverse way (r=-0.30, P<0.0001).

    Conclusion:

    No close relationships were seen between the three tests of endothelium-dependent vasodilation, suggesting that they each contribute with unique information on vasoreactivity. EDV, EIDV and FMD, but not PAT, were related to the Framingham score, suggesting that vasoreactivity in some vascular beds are related to cardiovascular risk in middle-aged individuals.

  • 240.
    Lind, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Andersson, P. E.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Fugmann, Andreas
    Hänni, Arvo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Reneland, R.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Linde, Torbjörn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lithell, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    The haemodynamic response to hyperinsulinaemia in hypertensive subjects1999Ingår i: Journal of Human Hypertension, ISSN 0950-9240, E-ISSN 1476-5527, Vol. 13, nr 1, s. 41-45Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In order to study if the vasodilatory action of insulin is impaired in essential hypertension, 24 untreated patients were challenged with a 2 h euglycaemic hyperinsulinaemic clamp (56 E/m2). Cardiac index (CI) was measured by thoracic impedance cardiography and leg blood flow (LBF) by Doppler ultrasound. During the clamp procedure a significant decline in blood pressure was seen (3.0-5.6% over 120 min, P < 0.001). However, no significant effects on ejection fraction (+6 +/- 8 s.d.%), CI (-1 +/- 2%), heart rate (+2 +/- 1%) or total peripheral resistance (TPRI, -0.5 +/- 2%) were found. LBF increased by 22 +/- 35% (P < 0.005). These haemodynamic effects of insulin were not related to age, sex, body mass index, blood pressure or the insulin-mediated glucose uptake during the clamp. In conclusion, insulin increased LBF, but no changes in CI and TPRI were seen in the hypertensive patients. Furthermore, no association between the ability of insulin to induce vasodilatation and to promote glucose uptake was seen.

  • 241.
    Lind, Lars
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Andren, Bertil
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Heart rate recovery after exercise is related to the insulin resistance syndrome and heart rate variability in elderly men.2002Ingår i: Am Heart J, ISSN 1097-6744, Vol. 144, nr 4, s. 666-72Artikel i tidskrift (Refereegranskat)
  • 242.
    Lind, Lars
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Andrén, Bertil
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Klinisk fysiologi.
    Arnlöv, Johan
    Institutionen för folkhälso- och vårdvetenskap.
    The Doppler-derived myocardial performance index is determined by both left ventricular systolic and diastolic function as well as by afterload and left ventricular mass.2005Ingår i: Echocardiography, ISSN 0742-2822, Vol. 22, nr 3, s. 211-6Artikel i tidskrift (Refereegranskat)
  • 243.
    Lind, Lars
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Andrén, Bertil
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Klinisk fysiologi Hj-lung, G H.
    Sundström, Johan
    Institutionen för folkhälso- och vårdvetenskap.
    The stroke volume/pulse pressure ratio predicts coronary heart disease mortality in a population of elderly men.2004Ingår i: J Hypertens, ISSN 0263-6352, Vol. 22, nr 5, s. 899-905Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The stroke volume to pulse pressure ratio (SV/PP), a measure of total arterial compliance, predicts adverse cardiovascular events in hypertensive subjects. The relations to cardiovascular risk factors and its predictive capacity in the general population are not known. METHOD AND RESULTS: In 1970-73, all 50-year-old men living in Uppsala County, Sweden, were invited to a health survey assessing cardiovascular risk factors. At a reinvestigation 20 years later, 470 subjects underwent an echocardiographic examination, hyperinsulinaemic euglycaemic clamp, oral glucose tolerance test and measurements of blood pressure and lipids. They were thereafter followed for a median of 7.2 years. Serum triglycerides and post-load glucose and insulin levels at age 50 were predictors of SV/PP ratio measured 20 years later (P < 0.05-0.001). At age 70, SV/PP was related to serum non-esterified fatty acids, post-load glucose and insulin levels and insulin sensitivity (P < 0.05-0.001). SV/PP was reduced in subjects with concentric left ventricular hypertrophy (LVH, P < 0.01), and in subjects with a low E-wave to A-wave (E/A) ratio (P < 0.001). The SV/PP ratio predicted mortality from coronary heart disease [hazard ratio 0.54, 95% confidence interval 0.30-0.97 for a one standard deviation (1SD) increase in ln(SV/PP)] independently of left ventricular mass and other major cardiovascular risk factors. Pulse pressure or total peripheral resistance were not significant predictors for future mortality from coronary heart disease. CONCLUSION: The SV/PP ratio was related to main components of the insulin resistance syndrome, concentric LVH and a low E/A ratio. Furthermore, the SV/PP ratio was an independent predictor of mortality from coronary heart disease in a community-based sample of men aged 70.

  • 244.
    Lind, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Carlsson, Axel C.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Alfred Nobels Alle 23, S-14152 Huddinge, Sweden..
    Siegbahn, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Dalarna Univ, Dept Hlth & Social Sci, S-79188 Falun, Sweden..
    Impact of physical activity on cardiovascular status in obesity2017Ingår i: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 47, nr 2, s. 167-175Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background We have recently shown that being physically active (PA) counteracts, but not eliminates the increased risk of future cardiovascular disease in overweight and obese subjects. To investigate this further, we studied the impact of being normal weight, overweight and obese on multiple markers of subclinical cardiovascular disease in relation to physical activity. Materials and methods At age 70, 1016 subjects were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Being PA was defined as performing regular heavy exercise (self-reported). According to body mass index (BMI)/PA groups, the participants were categorized as PA/normal weight (BMI < 25 kg/m(2), n = 104), non-PA/normal weight (n = 234), PA/overweight (BMI 25-29.9 kg/m(2), n = 133), non-PA/overweight (n = 295), PA/obese (BMI = 30 kg/m(2), n = 54) and non-PA/obese (n = 169). Several different measurements of endothelial reactivity and arterial compliance (plethysmography and ultrasound), cartotid artery atherosclerosis and echocardiography were performed, and seven markers of coagulation/ fibrinolysis were measured. Results Physically active subjects with obesity showed impaired vasoreactivity in the forearm resistance vessels, increased left ventricular mass and impaired left ventricular systolic and diastolic functions, together with impaired coagulation/fibrinolysis when compared to PA/normal-weight subjects (P < 0.05 to < 0.001). The majority of these disturbances were seen also in PA/overweight subjects when compared to PA/normal-weight subjects (P < 0.05 to < 0.001). Conclusions Our data provide additional support for the notion that an increased level of self-reported physical activity does not fully eliminate the deleterious cardiovascular consequences associated with overweight and obesity.

  • 245.
    Lind, Lars
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Carlstedt, F
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Rastad, J
    Institutionen för kirurgiska vetenskaper.
    Stiernström, H
    Institutionen för kirurgiska vetenskaper. Anaesthesiology and Intensive Care.
    Stridsberg, M
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Clinical Chemistry.
    Ljunggren, Ö
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Wide, L
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Clinical Chemistry.
    Larsson, A
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Clinical Chemistry.
    Hellman, P
    Institutionen för kirurgiska vetenskaper.
    Ljunghall, S
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Hypocalcemia and parathyroid hormone secretion in critically ill patients2000Ingår i: Crit Care Med, Vol. 28, s. 93-99Artikel i tidskrift (Refereegranskat)
  • 246.
    Lind, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Elmstahl, Solve
    Bergman, Ebba
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Englund, Martin
    Lindberg, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Lungmedicin och allergologi.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Nilsson, Peter M.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    EpiHealth: a large population-based cohort study for investigation of gene-lifestyle interactions in the pathogenesis of common diseases2013Ingår i: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 28, nr 2, s. 189-197Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The most common diseases affecting middle-aged and elderly subjects in industrialized countries are multigenetic and lifestyle related. Several attempts have been made to study interactions between genes and lifestyle factors, but most such studies lack the power to examine interactions between several genes and several lifestyle components. The primary objective of the EpiHealth cohort study is to provide a resource to study interactions between several genotypes and lifestyle factors in a large cohort (the aim is 300,000 individuals) derived from the Swedish population in the age range of 45-75 years regarding development of common degenerative disorders, such as cardiovascular diseases, cancer, dementia, joint pain, obstructive lung disease, depression, and osteoporotic fractures. The study consists of three parts. First, a collection of data on lifestyle factors by self-assessment using an internet-based questionnaire. Second, a visit to a test center where blood samples are collected and physiological parameters recorded. Third, the sample is followed for occurrence of outcomes using nationwide medical registers. This overview presents the study design and some baseline characteristics from the first year of data collection in the EpiHealth study.

  • 247.
    Lind, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Elmstahl, Solve
    Lund Univ, Malmo Univ Hosp, Dept Clin Sci, Div Geriatr Med, Malmo, Sweden.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA.
    Cardiometabolic Proteins Associated with Metabolic Syndrome2019Ingår i: Metabolic Syndrome and Related Disorders, ISSN 1540-4196, E-ISSN 1557-8518Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Although metabolic syndrome (MetS) was described in the late 80s, the molecular mechanisms underlying clustering of risk factors in certain individuals are not fully understood. The present study used targeted proteomics to establish cardiometabolic proteins related to all MetS components, thereby providing new hypotheses regarding pathways involved in the pathogenesis of MetS.

    Methods: In the EpiHealth study, 249 cardiometabolic proteins were measured by proximity extension assay (PEA) and related to the five MetS components [consensus-modified National Cholesterol Education Program (NCEP) criteria] in 2,444 participants aged 45-75 years (50% women).

    Results: Thirty-one proteins were associated with systolic blood pressure following adjustment for age and sex (P < 0.000040, taking multiple testing into account). The corresponding number of proteins significantly associated with fasting glucose, waist circumference, high-density lipoprotein cholesterol, and serum triglycerides were 58, 132, 127, and 148. Twenty-two proteins were significantly related to all 5 MetS components, and of those, 20 were with MetS as a binary outcome (n = 600, 24% of the sample) following adjustment for age, sex, fat mass, and lifestyle factors (alcohol intake, smoking, education, and exercise habits).

    Conclusion: Using targeted proteomics, we identified 20 proteins reflecting a range of pathways, such as immunomodulation at different levels; regulation of adipocyte differentiation; lipid, carbohydrate, and amino acid metabolism; or insulin-like growth factor signaling, to be strongly associated with MetS independently of fat mass and lifestyle factors. Whether some of these proteins are causally involved in the pathogenesis of clustering of multiple risk factors in the same individual remains to be investigated.

  • 248.
    Lind, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Elmstahl, Solve
    Lund Univ, Malmo Univ Hosp, Dept Hlth Sci, Div Geriatr Med, Malmo, Sweden..
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden..
    Change in Body Weight from Age 20 Years Is a Powerful Determinant of the Metabolic Syndrome2017Ingår i: Metabolic Syndrome and Related Disorders, ISSN 1540-4196, E-ISSN 1557-8518, Vol. 15, nr 3, s. 112-117Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Higher body weight is a well-known determinant of the metabolic syndrome (MetS) and its components. It is however less well studied how the change in weight from age 20 years to middle age or old age affects MetS development. Methods: In the community-based EpiHealth (n = 19,000, age range 45 to 75 years, 56% females) and PIVUS (n = 1000, all aged 70 years, 50% females) studies, the participants were asked about their body weight at age 20 years. Data were collected to determine MetS prevalence (NCEP ATP III criteria). Results: In EpiHealth, the probability of having MetS increased fairly linearly with increasing weight from age 20 in the obese [odds ratios (OR) 1.04 per kg change in weight, 95% confidence interval (CI) 1.03-1.05, P < 0.0001], as well as in the overweight (OR 1.15, 95% CI 1.14-1.17, P < 0.0001) and normal-weight (OR 1.18, 95% CI 1.14-1.21, P < 0.0001), subjects after adjustment for age, sex, body mass index (BMI) at age 20, alcohol intake, smoking, education, and exercise habits. Also in the PIVUS study, the change in weight over 50 years was related to prevalent MetS (OR 1.08 per kg change in weight, 95% CI 1.06-1.10, P < 0.0001). In both studies, self-reported BMI at age 20 was related to prevalent MetS. Conclusion: Self-reported weight gain from age 20 was strongly and independently associated with prevalent MetS both in middle age or old age. Interestingly, this relationship was not restricted only to obese subjects. Our data provide additional support for the importance of maintaining a stable weight throughout life.

  • 249.
    Lind, Lars
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Eriksson, Mats
    Institutionen för kirurgiska vetenskaper.
    Influence of nervous blockade on insulin-mediated glucose uptake in the human forearm.2003Ingår i: Metabolism, ISSN 0026-0495, Vol. 52, nr 4, s. 413-7Artikel i tidskrift (Refereegranskat)
  • 250.
    Lind, Lars
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Fors, Nilla
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Hall, Jan
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Marttala, Kerstin
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Stenborg, Anna
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    A comparison of three different methods to evaluate endothelium-dependent vasodilation in the elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study.2005Ingår i: Arterioscler Thromb Vasc Biol, ISSN 1524-4636, Vol. 25, nr 11, s. 2368-75Artikel i tidskrift (Övrigt vetenskapligt)
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