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Circulating 25-hydroxy-vitamin D and risk of cardiovascular disease: a meta-analysis of prospective studies.

ABSTRACT: Vitamin D status has been linked to the risk of cardiovascular disease (CVD). However, the optimal 25-hydroxy-vitamin D (25[OH]-vitamin D) levels for potential cardiovascular health benefits remain unclear.We searched MEDLINE and EMBASE from 1966 through February 2012 for prospective studies that assessed the association of 25(OH)-vitamin D concentrations with CVD risk. A total of 24 articles met our inclusion criteria, from which 19 independent studies with 6123 CVD cases in 65 994 participants were included for a meta-analysis. In a comparison of the lowest with the highest 25(OH)-vitamin D categories, the pooled relative risk was 1.52 (95% confidence interval, 1.30-1.77) for total CVD, 1.42 (95% confidence interval, 1.19-1.71) for CVD mortality, 1.38 (95% confidence interval, 1.21-1.57) for coronary heart disease, and 1.64 (95% confidence interval, 1.27-2.10) for stroke. These associations remained strong and significant when analyses were limited to studies that excluded participants with baseline CVD and were better controlled for season and confounding. We used a fractional polynomial spline regression analysis to assess the linearity of dose-response association between continuous 25(OH)-vitamin D and CVD risk. The CVD risk increased monotonically across decreasing 25(OH)-vitamin D below ?60 nmol/L, with a relative risk of 1.03 (95% confidence interval, 1.00-1.06) per 25-nmol/L decrement in 25(OH)-vitamin D.This meta-analysis demonstrated a generally linear, inverse association between circulating 25(OH)-vitamin D ranging from 20 to 60 nmol/L and risk of CVD. Further research is needed to clarify the association of 25(OH)-vitamin D higher than 60 nmol/L with CVD risk and assess causality of the observed associations.

SUBMITTER: Wang L

PROVIDER: S-EPMC3510675 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Circulating 25-hydroxy-vitamin D and risk of cardiovascular disease: a meta-analysis of prospective studies.

Wang Lu L Song Yiqing Y Manson Joann E JE Pilz Stefan S März Winfried W Michaëlsson Karl K Lundqvist Annamari A Jassal Simerjot K SK Barrett-Connor Elizabeth E Zhang Cuilin C Eaton Charles B CB May Heidi T HT Anderson Jeffrey L JL Sesso Howard D HD

Circulation. Cardiovascular quality and outcomes 20121113 6

<h4>Background</h4>Vitamin D status has been linked to the risk of cardiovascular disease (CVD). However, the optimal 25-hydroxy-vitamin D (25[OH]-vitamin D) levels for potential cardiovascular health benefits remain unclear.<h4>Methods and results</h4>We searched MEDLINE and EMBASE from 1966 through February 2012 for prospective studies that assessed the association of 25(OH)-vitamin D concentrations with CVD risk. A total of 24 articles met our inclusion criteria, from which 19 independent stu ...[more]

PMID: 23149428

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Project description:BackgroundThe association of APOE genotype with circulating apolipoprotein E (ApoE) concentration and cardiovascular disease (CVD) risk is well established. However, the relationship of circulating ApoE concentration and CVD has received little attention.Methods and findingsTo address this, we measured circulating ApoE concentration in 9,587 individuals (with 1,413 CVD events) from three studies with incident CVD events: two population-based studies, the English Longitudinal Study of Ageing (ELSA) and the men-only Northwick Park Heart Study II (NPHSII), and a nested sub-study of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). We examined the association of circulating ApoE with cardiovascular risk factors in the two population-based studies (ELSA and NPHSII) and the relationship between ApoE concentration and coronary heart disease and stroke in all three studies. Analyses were carried out within study, and, where appropriate, pooled effect estimates were derived using meta-analysis. In the population-based samples, circulating ApoE was associated with systolic blood pressure (correlation coefficient 0.08, p < 0.001, in both ELSA and NPHSII), total cholesterol (correlation coefficient 0.46 and 0.34 in ELSA and NPHSII, respectively; both p < 0.001), low-density lipoprotein cholesterol (correlation coefficient 0.30 and 0.14, respectively; both p < 0.001), high-density lipoprotein (correlation coefficient 0.16 and -0.14, respectively; both p < 0.001), and triglycerides (correlation coefficient 0.43 and 0.46, respectivly; both p < 0.001). In NPHSII, ApoE concentration was additionally associated with apolipoprotein B (correlation coefficient 0.13, p = 0.001) and lipoprotein(a) (correlation coefficient -0.11, p < 0.001). In the pooled analysis of ASCOT, ELSA, and NPHSII, there was no association of ApoE with CVD events; the odds ratio (OR) for CVD events per 1-standard-deviation higher ApoE concentration was 1.02 (95% CI 0.96, 1.09). After adjustment for cardiovascular risk factors, the OR for CVD per 1-standard-deviation higher ApoE concentration was 0.97 (95% CI 0.82, 1.15). Limitations of these analyses include a polyclonal method of ApoE measurement, rather than isoform-specific measurement, a moderate sample size (although larger than any other study to our knowledge and with a long lag between ApoE measures), and CVD events that may attenuate an effect.ConclusionsIn the largest study to date on this question, we found no evidence of an association of circulating ApoE concentration with CVD events. The established association of APOE genotype with CVD events may be explained by isoform-specific functions as well as other mechanisms, rather than circulating concentrations of ApoE.

Project description:Background: Cardiovascular disease (CVD) risk factors are associated with low serum 25 hydroxyvitamin D (25(OH)D) concentrations in observational studies; however, clinical trial findings are inconsistent. Objective: We assessed the effect of vitamin D supplementation and increased serum 25(OH)D concentrations on CVD risk factors in a systemic review and meta-analysis of randomized controlled trials (RCTs). Design: MEDLINE, CINAHL, EMBASE, and Google Scholar were searched for RCTs that evaluated vitamin D supplementation and cardiovascular outcomes [blood pressure, parathyroid hormone (PTH), serum high-sensitivity C-reactive protein (hs-CRP), total cholesterol, high and low density lipoprotein (HDL and LDL, respectively), triglycerides, peak wave velocity (PWV) and Augmentation Index (AI)] from 1992 through 2017. Meta-analysis was based on a random-effects model and inverse variance method to calculate standardized mean difference (SMD) as effect sizes, followed by a leave-one-out method for sensitivity analysis. Risk of publication bias was assessed using Cochrane checklist and Begg funnel plots. The systematic review is registered as CRD42015025346. Results: We identified 2341 studies from which 81 met inclusion criteria. The meta-analysis indicated a significant reduction in systolic blood pressure (SMD = -0.102 ± 0.04 mmHg, 95% confidence interval (CI), -0.20 to -0.03), diastolic blood pressure (SMD = -0.07 ± 0.03 mmHg, 95% CI, -0.14 to -0.006), serum PTH (SMD = -0.66 ± 0.08 ng/L, 95% CI, -0.82 to -0.49), hs-CRP (SMD = -0.20 ± 0.07 mg/L, 95% CI, -0.34 to -0.06), total cholesterol (SMD = -0.15 ± 0.06 mmol/L, 95% CI, -0.25 to -0.04), LDL (SMD = -0.10 ± 0.05 mmol/L, 95% CI, -0.20 to -0.003), triglycerides (SMD = -0.12 ± 0.06 mmol/L, 95% CI, -0.23 to -0.003) and a significant increase in HDL (SMD = 0.09 ± 0.04 mmol/L, 95% CI, 0.00 to 0.17) with vitamin D supplementation. These findings remained significant in sensitivity analyses for blood pressure, lipid profile, serum PTH, and serum hs-CRP. There was no significant effect of vitamin D supplementation on PWV (SMD = -0.20 ± 0.13 m/s, 95% CI, -0.46 to 0.06, p = 0.14) and AI (SMD = -0.09 ± 0.14%, 95% CI, -0.37 to 0.19, p = 0.52) for vitamin D supplemented groups. Conclusion: These findings suggest that vitamin D supplementation may act to protect against CVD through improving risk factors, including high blood pressure, elevated PTH, dyslipidemia, and inflammation.

Dataset Information

Circulating 25-hydroxy-vitamin D and risk of cardiovascular disease: a meta-analysis of prospective studies.

Publications

Circulating 25-hydroxy-vitamin D and risk of cardiovascular disease: a meta-analysis of prospective studies.

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