Vitamin D deficiency was associated with several cardiovascular-related diseases, including hypertension, coronary artery disease, cardiomyopathy, and diabetes

From the American Journal of Cardiology on 3 Feb 2012.Vitamin D and CVD - AJC Feb 2012.pdf

Vitamin D Deficiency and Supplementation and Relation to Cardiovascular Health

It is very interesting in that, whilst it was an observational study, it looked not only at serum Vitamin D levels, but also at the relationship of D3 supplementation to CVD. It suggests a strong association between supplementation and reduced CVD, particularly among those who were deficient at the baseline.

See abstract and discussion below:

"Recent evidence supports an association between vitamin D deficiency and hypertension, peripheral vascular disease, diabetes mellitus, metabolic syndrome, coronary artery disease, and heart failure. The effect of vitamin D supplementation, however, has not been well studied. We examined the associations between vitamin D deficiency, vitamin D supplementation, and patient outcomes in a large cohort. Serum vitamin D measurements for 5 years and 8 months from a large academic institution were matched to patient demographic, physiologic, and disease variables. The vitamin D levels were analyzed as a continuous variable and as normal (≥30 ng/ml) or deficient (<30 ng/ml). Descriptive statistics, univariate analysis, multivariate analysis, survival analysis, and Cox proportional hazard modeling were performed. Of 10,899 patients, the mean age was 58 ± 15 years, 71% were women (n = 7,758), and the average body mass index was 30 ± 8 kg/m². The mean serum vitamin D level was 24.1 ± 13.6 ng/ml. Of the 10,899 patients, 3,294 (29.7%) were in the normal vitamin D range and 7,665 (70.3%) were deficient. Vitamin D deficiency was associated with several cardiovascular-related diseases, including hypertension, coronary artery disease, cardiomyopathy, and diabetes (all p <0.05). Vitamin D deficiency was a strong independent predictor of all-cause death (odds ratios 2.64, 95% confidence interval 1.901 to 3.662, p <0.0001) after adjusting for multiple clinical variables. Vitamin D supplementation conferred substantial survival benefit (odds ratio for death 0.39, 95% confidence interval 0.277 to 0.534, p <0.0001). In conclusion, vitamin D deficiency was associated with a significant risk of cardiovascular disease and reduced survival. Vitamin D supplementation was significantly associated with better survival, specifically in patients with documented deficiency."

Discussion

Vitamin D has important physiologic functions beyond bone and calcium metabolism. Because vitamin D receptors are involved in the expression of nearly 3,000 human genes, a deficiency could potentially affect numerous disease processes.  Cardiovascular, oncologic, and immunologic disorders have been associated with vitamin D deficiency. Our study showed an association between vitamin D deficiency and many cardiovascular disease states, including hypertension, coronary artery disease, cardiomyopathy, and cardiovascular risk factors, such as hypertension, diabetes mellitus, and hyperlipidemia.

Numerous studies and meta-analyses have suggested that vitamin D deficiency has a negative association with survival; however, the effect of vitamin D supplementation on overall mortality has not been studied. Our findings are consistent with these previous studies, suggesting poorer patient outcomes for patients with vitamin D deficiency. In addition, our data further extend these findings by demonstrating better survival with vitamin D supplementation. The benefits of vitamin D supplementation on survival were significant for those patients with a documented deficiency. This benefit was independent of the concomitant use of other cardioprotective drugs such as aspirin or statins.

These findings could have clinical implications for the usual recommended daily allowance for vitamin D. The regular intake of the recommended 400 IU/day might be adequate to avoid deficiency in many people, and supplementation of _1,000 IU/day might be required to achieve optimal levels.

When included in survival and hazard models with several disease states, vitamin D deficiency is a strong independent predictor of all-cause death. Several studies have reported on the association between obesity and low vitamin D levels, which we also observed in our study cohort. Because the prevalence of obesity is increasing in the United States, as well as in many other developed and emerging nations, vitamin D deficiency could be increasingly common in the future. In addition, our study showed an association between vitamin D deficiency and unfavorable serum lipid values.

Because vitamin D deficiency is widespread, strategies directed at population-based supplementation programs could prove beneficial. To date, however, prospective studies evaluating vitamin D supplementation are few and have not consistently shown benefit. It is possible that the lack of benefit in these studies resulted from suboptimal levels of vitamin D supplementation or other unknown factors. Many previous studies of vitamin D supplementation have used doses of 400 to 800 IU, which might not be adequate to ensure optimal serum levels, with more appropriate daily supplement doses suggested as 1,000 to 2,000 IU. Nevertheless, the growing body of observational data demonstrating relatively high rates of low vitamin D serum levels warrant additional welldesigned studies to investigate the relation between vitamin D and cardiovascular health.

Additional investigation with long-term prospective studies of various vitamin D dosage levels in both healthy and diseased populations are indicated to firmly establish the role of vitamin D supplementation on overall outcomes and mortality. Our study suggests a significant association of vitamin D supplement use and improved survival in deficient subjects, supporting the potential benefit of this intervention. Recent guidelines for the evaluation and treatment of vitamin D deficiency have been published that can help the clinician with patient treatment.

 This was a retrospective, observational study with a selected population, introducing possible selection bias. The study population was derived from patients who had had their vitamin D levels measured at a hospital laboratory and who were patients in a cardiovascular practice and included in its electronic medical records. Extrapolation to other populations might not be appropriate. Also, isolated vitamin D measurement might not reflect long-term levels. We made an arbitrary decision to use the lowest vitamin D measurement for analysis because this value was thought to most likely represent the subjects’ baseline nonsupplemented level. We were unable to accurately associate the timing of vitamin D measurement and supplement initiation. The dose and duration of vitamin D supplementation were not analyzed, and patient compliance was not measured. Inclusion of vitamin D in multivitamin supplements was not considered.

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See Am J Cardiol 2012;109:359–363