Boston, MA - Vitamin-D deficiency appears to be a risk factor for developing cardiovascular disease, a new study suggests [1].

The study, published online January 7, 2008 in Circulation, was conducted by a group led by Dr Thomas Wang (Massachusetts General Hospital, Boston). They conclude: "These findings may have potentially broad public-health implications, given the high prevalence of vitamin-D deficiency in developed countries, the contribution of lifestyle and geography to vitamin-D status, and the ease, safety, and low cost of treating vitamin-D deficiency."

They add that further clinical and experimental studies may be warranted to validate their findings, to investigate the mechanisms underlying increased cardiovascular risk, and to determine whether correction of vitamin-D deficiency could contribute to the prevention of cardiovascular disease.

Wang et al explain that vitamin-D deficiency is highly prevalent in the US and worldwide, affecting as many as one-third to one-half of otherwise-healthy middle-aged to elderly adults, and that limited cutaneous synthesis due to inadequate sun exposure or pigmented skin and inadequate dietary intake are the principal causes of low vitamin-D levels.

They note that although the best-characterized sequelae of vitamin-D deficiency involve the musculoskeletal system, a growing body of evidence suggests that low levels of vitamin D may adversely affect the cardiovascular system. Vitamin-D receptors have a broad tissue distribution that includes vascular smooth muscle, endothelium, and cardiomyocytes, and there are higher rates of coronary heart disease and hypertension with increasing distance from the equator, a phenomenon that has been attributed to the higher prevalence of vitamin-D deficiency in regions with less exposure to sunlight.

But they caution that prospective data are needed, because vitamin-D deficiency could be a consequence of cardiovascular disease rather than a cause. Thus, they prospectively investigated the relation of vitamin-D status to the incidence of cardiovascular events in a large, ambulatory, community-based population from the Framingham Offspring Study who were all free of cardiovascular disease at baseline.

In the 1739 participants (mean age 59 years; 55% women; all white), vitamin-D status was assessed by measuring 25-dihydroxyvitamin-D (25-OH D) levels. Overall, 28% of individuals had levels below 15 ng/mL, and 9% had levels below 10 ng/mL, thresholds that characterize varying degrees of vitamin-D deficiency.

During a mean follow-up of 5.4 years, 120 individuals developed a first cardiovascular event. After adjustment for conventional cardiovascular risk factors, individuals with 25-OH D levels below 15 ng/mL had an increased risk for incident cardiovascular events compared with those with 25-OH D levels above 15 ng/mL. The higher risk associated with vitamin-D deficiency was particularly evident among individuals with hypertension, in whom 25-OH D levels below 15 ng/mL were associated with a twofold risk of cardiovascular events. But there was no correlation seen in participants without hypertension.

There was also a graded increase in cardiovascular risk as levels of 25-OH D decreased, and further adjustment for C-reactive protein, physical activity, or vitamin use did not affect the findings.

The authors note that these data indicate that increased cardiovascular risk is present at 25-OH D levels (<15 ng/mL) compatible with at least moderate vitamin-D deficiency. They add that the present findings extend the results of smaller, cross-sectional studies that have examined the association between vitamin-D status and cardiovascular risk and have shown 25-OH D levels in individuals with MI, stroke, heart failure, and cardiovascular disease.

On the possible mechanisms, Wang et al point out that 1,25-OH D is involved in the regulation of the renin-angiotensin axis and putative vascular effects of vitamin D are wide-ranging and include modulation of smooth-muscle-cell proliferation, inflammation, and thrombosis.

They add that potential interaction between vitamin-D deficiency and hypertension suggested in this study fits in with the observation that both hypertension and vitamin-D deficiency may influence cardiac and vascular remodeling and with data suggesting that vitamin-D deficiency directly promotes the development of hypertension.

They point out that in small clinical trials, vitamin-D supplementation has promoted reductions in blood pressure, left ventricular hypertrophy, and inflammatory cytokines, although vitamin-D supplements were not associated with a reduction in cardiovascular events in the Women's Health Initiative. But they add that the Women's Health Initiative was a fracture-prevention trial and was not designed to evaluate cardiovascular risk; the dose of vitamin D used was far below the amount necessary to correct vitamin-D deficiency; patients in the placebo arm were also allowed to take vitamin-D supplements, which could have masked any benefit; and the trial did not address whether vitamin-D supplementation benefited individuals with vitamin-D deficiency, because enrollment was performed irrespective of vitamin-D status. They note, however, that vitamin D did appear to reduce cardiovascular risk in obese individuals, who are prone to endogenous vitamin-D deficiency, and also in those with multiple coronary risk factors.