Circulating 25-hydroxy-vitamin D and risk of cardiovascular disease: a meta-analysis of prospective studies.
Circ Cardiovasc Qual Outcomes. 2012 Nov;5(6):819-29. doi: 10.1161/CIRCOUTCOMES.112.967604. Epub 2012 Nov 13.
Wang L, Song Y, Manson JE, Pilz S, März W, Michaëlsson K, Lundqvist A, Jassal SK, Barrett-Connor E, Zhang C, Eaton CB, May HT, Anderson JL, Sesso HD.
Brigham and Women’s Hospital, Boston, MA 02215, USA. luwang at rics.bwh.harvard.edu
BACKGROUND: Vitamin D status has been linked to the risk of cardiovascular disease (CVD). However, the optimal 25-hydroxy-vitamin D (25OH-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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