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Vascular disease

Vitamin D inadequacy supports CVD risk factors such as hypertension, hyperlipidemia, and thrombophilia. The effect of vitamin D status on ventricular arrhythmia, and its potential to affect the incidence of sudden death, is less clear-cut. In the study by Deo et al., the combination of low 25(OH)D and elevated PTH has been reported to be associated with more than 2fold increase in risk in sudden cardiac death in otherwise healthy subjects (1). This might be of particular importance in patients with renal impairment. Although CVD consists of a diverse range of conditions with multifactorial causes, it is equally evident that vitamin D metabolism influences a wide range of biological processes, so it is plausible that vitamin D status could be associated with virtually any form of CVD. For example, the functional status of heart failure patients is proportional to vitamin D status, as might be expected on the basis of direct effects of vitamin D on the myocardium (2). This effect is amplified in the setting of chronic renal impairment where vitamin D metabolism is further impaired.

The quality of the evidence supporting an association between vitamin D status and CVD ranges from cross-sectional to prospective epidemiological studies. The consistency of the findings has been maintained, as illustrated by the most recently reported cohort from the Copenhagen City Heart study (3). Consequently, meta-analyses have consistently revealed an inverse relationship between vitamin D status and CVD events (2). CVD is the leading cause of death in many of the conditions associated with inadequate vitamin D levels (Fig. D11). As a result, total mortality is inversely proportional to vitamin D status in several situations including hypertension, insulin resistance, diabetes, and established heart failure.

Unfortunately, randomized controlled trials of vitamin D replacement have not lived up to expectations. Lipids showed little change in response to vitamin D and endothelial function was not improved. CVD outcomes studies have been difficult to interpret because the intervention regime frequently included calcium supplementation. This led to concern about possible arterial calcification and other detrimental effects. Some trials have suggested that calcium supplements could exacerbate the risk of CVD. Systematic review suggests that vitamin D in high doses may exert a mild protective effect on CVD (4) while calcium supplements are probably neutral.


1.     Deo R, Katz R, Shlipak MG, Sotoodehnia N, Psaty BM, Sarnak MJ et al. Vitamin D, parathyroid hormone, and sudden cardiac death: results from the Cardiovascular Health Study. Hypertension 2011;58:1021-8.
2.     Meems LM, van der HP, van Gilst WH, de Boer RA. Vitamin D biology in heart failure: molecular mechanisms and systematic review. Curr Drug Targets 2011;12:29-41.
3.     Brondum-Jacobsen P, Benn M, Jensen GB, Nordestgaard BG. 25-hydroxyvitamin d levels and risk of ischemic heart disease, myocardial infarction, and early death: population-based study and meta-analyses of 18 and 17 studies. Arterioscler Thromb Vasc Biol 2012;32:2794-802.
4.     Wang L, Manson JE, Song Y, Sesso HD. Systematic review: Vitamin D and calcium supplementation in prevention of cardiovascular events. Ann Intern Med 2010;152:315-23.