Editors' ChoiceCardiovascular Disease

Vitamin D—A Passenger, Not a Driver in Cardiovascular Disease

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Science Translational Medicine  17 Sep 2014:
Vol. 6, Issue 254, pp. 254ec160
DOI: 10.1126/scitranslmed.3010408

Epidemiological studies and the popular media suggest that vitamin D deficiency, estimated by measuring 25-hydroxyvitamin D in blood, is linked to increased risk of ischemic heart disease and stroke. However, randomized clinical trials testing whether vitamin D supplementation decreases the risk of these diseases have been surprisingly disappointing—but it is not understood why. To get at this question, Ooi et al. tested whether vitamin D deficiency caused a poor lipid profile (which in turn would cause heart disease or stroke) or vice versa. Their new results suggest that disease-causing atherogenic lipids [nonfasting remnant cholesterol and low-density lipoprotein (LDL) cholesterol] also decrease vitamin D levels.

Ooi et al. cleverly used the data from the Copenhagen General Population Study and the Copenhagen City Heart Study to examine whether previously established genetic influencers of atherogenic lipids and decreased high-density lipoprotein (HDL) cholesterol determined 25-hydroxyvitamin D levels. They also examined the opposite question: whether previously established genetic predictors of 25-hydroxyvitamin D levels affected atherogenic lipids and HDL. They found that genetic influencers of cholesterol significantly predicted 25-hydroxyvitamin D levels. Each doubling of atherogenic lipids was significantly associated with lower 25-hydroxyvitamin D levels, although genetically lowered HDL was associated with higher 25-hydroxyvitamin D. In striking contrast, genetically lower levels of 25-hydroxyvitamin D did not predict concentrations of atherogenic lipids. The investigators concluded that elevated atherogenic lipids, but not HDL, contribute to the low 25-hydroxyvitamin D levels associated with heart disease and stroke.

The study has limitations, including an observational design, but is strengthened by sample size (85, 868 subjects) and conservative analytical approaches. These results suggest that low 25-hydroxyvitamin D levels are simply a secondary marker of elevated atherogenic lipids and raise doubt about the value of vitamin D supplementation for the prevention of cardiovascular disease.

E. M. Ooi et al., Elevated remnant cholesterol in 25-hydroxyvitamin D deficiency in the general population: A Mendelian randomization study. Circ. Cardiovasc. Genet. 10.1161/CIRCGENETICS.113.000416 (2014). [Abstract]

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