Jun 15, 2008
Further Evidence Supports Vitamin-D-Deficiency Link to CHD CME
June 11, 2008 — Further evidence that vitamin-D deficiency may increase the risk of heart disease has come from a new case-control study .
The study, published in the June 9, 2008 issue of the Archives of Internal Medicine, found that low levels of 25-dihydroxyvitamin-D (25[OH]D) were associated with a higher risk of myocardial infarction (MI) in a graded manner, even after researchers controlled for factors known to be associated with coronary artery disease.
The authors, led by Dr Edward Giovannucci (Harvard School of Public Health, Boston, MA), note that in most populations studied, the rate of cardiovascular death is elevated at higher latitudes, increases during the winter months, and is lower at high altitudes, a pattern consistent with an adverse effect of low levels of vitamin D, which are more prevalent at higher latitudes, during the winter, and at lower altitudes.
While alternative explanations for these observations are possible, they point out that a variety of plausible biological mechanisms support a role for vitamin D in heart disease. For example, the vitamin-D axis affects vascular smooth-muscle-cell proliferation, inflammation, vascular calcification, the renin-angiotensin system, and blood pressure.
To look at this issue further, they prospectively examined 25(OH)D concentrations in relation to risk of MI in a nested case-control study involving 18,225 men in the Health Professionals Follow-up Study (HPFS). The men were aged 40 to 75 years and were free of diagnosed cardiovascular disease at baseline.
During 10 years of follow-up, 454 men developed nonfatal MI or fatal coronary heart disease (cases), and 900 controls were selected matched for age, date of blood collection, and smoking status.
Results showed that men deficient in 25(OH)D were found to be at increased risk for MI compared with those considered to be sufficient in 25(OH)D (> 30 ng/mL).
Giovannucci et al emphasize that men with circulating 25(OH)D levels of at least 30 ng/mL had approximately half the risk of MI, independent of other cardiovascular risk factors, and this association was suggestively stronger for fatal CHD, although the number of cases was too small to make definitive conclusions.
They note that only 23% of the men in the HPFS had levels of 25(OH)D of at least 30 ng/mL, which is typical of many populations, and the prevalence of deficiency is even higher in subpopulations such as dark-skinned individuals and elderly persons. In individuals in sun-rich environments, where clothing or cultural practices do not appreciably limit vitamin-D production, 25(OH)D levels of 54 to 90 ng/mL are attained, they report, adding that it is not possible from these data to evaluate whether levels greater than 35 ng/mL would be associated with an even greater MI risk reduction.
While vitamin-D supplementation was not shown to affect cardiovascular risk in the Women's Health Initiative, the authors point out that the range of vitamin-D levels was much narrower in that study, which would have made it more difficult to detect any effect. They say that to increase 25(OH)D levels from 12 to 35.5 ng/mL would require approximately 3000 IU of vitamin D daily, and although such intakes may seem high by current standards, increasing evidence demonstrates no toxic effects at intakes below 10,000 IU/day. Because current sources of vitamin D provide much less (eg, a glass of milk has approximately 100 IU), those who achieve high levels such as 35 ng/mL naturally do so largely through sun exposure, they add.
If the association seen in this study is causal, which remains to be established, the amount of vitamin D required for optimal benefit may be much higher than would be provided by current recommendations (200-600 IU/day), especially in those with minimal sun exposure, Giovannucci et al comment. Thus, the present findings add further support that the current dietary requirements of vitamin D need to be increased to have an effect large enough for potential health benefits, they conclude.
This study was supported by the National Cancer Institute and the National Heart, Lung, and Blood Institute. Two of the study authors have obtained funding. Another study author is a consultant for Diasorin Corp.
Giovannucci E, Liu Y, Hollis BW, Rimm EB. 25-hydroxyvitamin D and risk of myocardial infarction in men. A prospective study. Arch Intern Med. 2008;168:1174-1180.