In their observational prospective study, Anderson et al reported a statistically significant inverse association between serum 25(OH) vitamin D and incident death, heart failure, coronary artery disease, myocardial infarction, and stroke. The investigators concluded that low serum levels of 25(OH) vitamin D might play a primary role in the development of cardiovascular diseases.

We would like to emphasize the possible confounding role of human adiposity, usually described by the proxy indicator body mass index (BMI). Anderson et al did not include BMI in their proportional-hazards models, and thus hazard ratios linking serum 25(OH) vitamin D levels and study outcomes were not adjusted for this confounding factor.

An inverse relation between serum 25(OH) vitamin D and BMI has been well documented in a number of studies. This is probably due to decreased bioavailability of vitamin D from cutaneous sources, because this vitamin is lipophilic and thus tends to deposit in adipose tissue.

Second, in a recent meta-analysis, Guh et al found obesity to be significantly associated with cardiovascular disease incidence. Hence, obesity and high BMI are associated with hypovitaminosis D and with cardiovascular disease, a double relation that can partly or totally confound the inverse relation between serum 25(OH) vitamin D and cardiovascular disease.

As an example, in a prospective study, Jassal et al found a crude hazard ratio of 0.82 (95% confidence interval 0.66 to 1.02) between a 1-SD increase in serum 25(OH) vitamin D and cardiovascular disease mortality, suggesting 18% decreased risk. After adjustment for age, gender, and BMI, the adjusted hazard ratio increased to 0.93 (95% confidence interval 0.76 to 1.14).

Anderson et al suggest that vitamin D deficiency represents an important new cardiovascular risk factor and hypothesize that it might play a causal role in the development of cardiovascular diseases. This suggestion is invalidated by a lack of appropriate adjustment for a major risk factor for low vitamin D status and cardiovascular disease. Available data in fact suggest that low vitamin D status would be a marker of an unhealthy lifestyle with a higher prevalence of obesity.

In conclusion, before electing vitamin D deficiency as a new cardiovascular risk factor, the issue of a causal relation between low vitamin D level and the development of cardiovascular disease should be more firmly documented, ideally through randomized trials.