Circulating 25-Hydroxy-Vitamin D and risk of cardiovascular disease: A meta-analysis of prospective studies

Lu Wang, Yiqing Song, Jo Ann E. Manson, Stefan Pilz, Winfried März, Karl Michaëlsson, Annamari Lundqvist, Simerjot K. Jassal, Elizabeth Barrett-Connor, Cuilin Zhang, Charles B. Eaton, Heidi T. May, Jeffrey L. Anderson, Howard D. Sesso

Research output: Contribution to journalArticle

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Abstract

Background-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. Methods and Results-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. Conclusions-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.

Original languageEnglish (US)
Pages (from-to)819-829
Number of pages11
JournalCirculation: Cardiovascular Quality and Outcomes
Volume5
Issue number6
DOIs
StatePublished - Nov 1 2012
Externally publishedYes

Fingerprint

Vitamin D
Meta-Analysis
Cardiovascular Diseases
Prospective Studies
Confidence Intervals
Insurance Benefits
MEDLINE
Causality
Coronary Disease
Stroke
Regression Analysis
Mortality
Research

Keywords

  • 25-hydroxy-vitamin D
  • Cardiovascular disease
  • Meta-analysis
  • Prospective study

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Circulating 25-Hydroxy-Vitamin D and risk of cardiovascular disease : A meta-analysis of prospective studies. / Wang, Lu; Song, Yiqing; Manson, Jo Ann E.; Pilz, Stefan; März, Winfried; Michaëlsson, Karl; Lundqvist, Annamari; Jassal, Simerjot K.; Barrett-Connor, Elizabeth; Zhang, Cuilin; Eaton, Charles B.; May, Heidi T.; Anderson, Jeffrey L.; Sesso, Howard D.

In: Circulation: Cardiovascular Quality and Outcomes, Vol. 5, No. 6, 01.11.2012, p. 819-829.

Research output: Contribution to journalArticle

Wang, L, Song, Y, Manson, JAE, Pilz, S, März, W, Michaëlsson, K, Lundqvist, A, Jassal, SK, Barrett-Connor, E, Zhang, C, Eaton, CB, May, HT, Anderson, JL & Sesso, HD 2012, 'Circulating 25-Hydroxy-Vitamin D and risk of cardiovascular disease: A meta-analysis of prospective studies', Circulation: Cardiovascular Quality and Outcomes, vol. 5, no. 6, pp. 819-829. https://doi.org/10.1161/CIRCOUTCOMES.112.967604
Wang, Lu ; Song, Yiqing ; Manson, Jo Ann E. ; Pilz, Stefan ; März, Winfried ; Michaëlsson, Karl ; Lundqvist, Annamari ; Jassal, Simerjot K. ; Barrett-Connor, Elizabeth ; Zhang, Cuilin ; Eaton, Charles B. ; May, Heidi T. ; Anderson, Jeffrey L. ; Sesso, Howard D. / Circulating 25-Hydroxy-Vitamin D and risk of cardiovascular disease : A meta-analysis of prospective studies. In: Circulation: Cardiovascular Quality and Outcomes. 2012 ; Vol. 5, No. 6. pp. 819-829.
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abstract = "Background-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. Methods and Results-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. Conclusions-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.",
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AU - Pilz, Stefan

AU - März, Winfried

AU - Michaëlsson, Karl

AU - Lundqvist, Annamari

AU - Jassal, Simerjot K.

AU - Barrett-Connor, Elizabeth

AU - Zhang, Cuilin

AU - Eaton, Charles B.

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N2 - Background-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. Methods and Results-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. Conclusions-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.

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