Vitamin D deficiency associated with cardiovascular risk

January 19, 2008 By Benjamin A. Olenchock, M.D. Ph.D. [mailto:bolenchock@partners.org]

Boston Most people associate vitamin D deficiency with the bony deformities of rickets. There is a growing appreciation, however, that less severe vitamin D deficiencies might play a role in other chronic illnesses including infectious diseases, cancer, and autoimmune diseases. New data from the Framingham heart study provides more evidence that vitamin D deficiency is associated with risk of cardiovascular disease.

Vitamin D is obtained through exposure to sunlight, or through ingestion in our diets or in supplements. Ultraviolet radiation converts a cholesterol metabolite to previtamin D3, which is then converted to vitamin D3. In countries far from the equator, vitamin D from fish oils is a major source. The definition of deficiency debated, and most studies have used a level of 25-hydroxyvitamin D (25-OH D) less than 20 ng/ml. However, there is evidence that levels >30 ng/ml are preferable. Estimates of vitamin D deficiency are as high as 40% in the general population, and almost 75% of internal medicine residents.

Researchers from the Framingham Offspring study prospectively collected 25-OH D levels in 1739 white individuals without cardiovascular disease or renal disease. For the primary analysis, vitamin D levels were a categorical variable, with cut-offs chosen a priori based on previously published studies. Participants were classified as deficient (<15 ng/ml) or sufficient (>15 ng/ml). Mean level was 19.7 ng/ml among all participants. Low 25-OH D levels were associated with obesity, cigarette smoking, higher systolic blood pressure, diabetes, higher ratio of total to HDL cholesterol, and lower intake of vitamin D or vitamins. Interesting, there was no correlation with physical activity.

Over a mean of 7.6 years follow up there were 120 cardiovascular events. A multivariate model was used to correlate 25-OH D status with cardiovascular risk, adjusting for age, sex, blood pressure, medications, diabetes, cigarette smoking, cholesterol, body mass index, and renal function. After adjustment, a 25-OH D level less than 15 ng/ml was independently associated with risk of a cardiovascular event (HR 1.62, CI 1.11 to 2.35, P=0.01). In a three-category model, where participants were classified as sufficient, deficient (10 to 15 ng/ml) or severely deficient (<10 ng/ml), severe deficiency was associated with even greater risk (HR 1.80, CI 1.05 to 3.08, P=0.01).

The mechanism by which vitamin D deficiency might increase risk of vascular disease is not entirely known. The authors cite data demonstrating that 1,25-OH D is important for suppression of the renin-angiotensin axis, and possible effects of hyperparathyroidism on myocyte function and vascular inflammation. The possibility always exists that an unmeasured confounder might explain the correlation seen in this study. Nonetheless, it is telling that the majority of participants in this study would qualify as vitamin-D deficient if a cut-off of 20 ng/ml were used, and the body of evidence linking vitamin-D deficiency with chronic illness is impressive.

Note: the recommended daily allowance of vitamin D is 400 IU/day, or 600 IU/day for people over 70 years old. To treat mild vitamin D deficiency requires 800 to 1000 IU daily for months, and for severe deficiency often 50,000 IU once per week for 2 months is necessary.