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Vitamin D and cardiovascular disease prevention

Key Points

  • The vitamin D receptor (VDR) and enzymes for vitamin D metabolism are expressed throughout the cardiovascular system

  • VDR and 1α-hydroxylase knockout mice have hypertension with myocardial hypertrophy and increased activity of the renin–angiotensin–aldosterone system

  • The molecular effects of VDR activation indicate various antiatherosclerotic and protective effects on the heart and on common cardiovascular risk factors

  • Observational studies have shown that low 25-hydroxyvitamin D levels are associated with an adverse cardiovascular risk profile and significantly increased risk of cardiovascular events

  • Mendelian randomization studies and randomized clinical trials have not shown significant effects of vitamin D on cardiovascular events, but these trials were not designed to investigate cardiovascular outcomes in vitamin D-deficient individuals

  • Vitamin D supplementation is currently not indicated for the purpose of cardiovascular disease prevention, but treatment of vitamin D deficiency is critical for skeletal health

Abstract

Vitamin D is a precursor of the steroid hormone calcitriol that is crucial for bone and mineral metabolism. Both the high prevalence of vitamin D deficiency in the general population and the identification of the vitamin D receptor in the heart and blood vessels raised interest in the potential cardiovascular effects of vitamin D. Experimental studies have demonstrated various cardiovascular protective actions of vitamin D, but vitamin D intoxication in animals is known to induce vascular calcification. In meta-analyses of epidemiological studies, vitamin D deficiency is associated with an increased cardiovascular risk. Findings from Mendelian randomization studies and randomized, controlled trials (RCTs) do not indicate significant effects of a general vitamin D supplementation on cardiovascular outcomes. Previous RCTs, however, were not adequately designed to address extraskeletal events, and did not focus on vitamin D-deficient individuals. Therefore, currently available evidence does not support cardiovascular benefits or harms of vitamin D supplementation with the commonly used doses, and whether vitamin D has cardiovascular effects in individuals with overt vitamin D deficiency remains to be evaluated. Here, we provide an update on clinical studies on vitamin D and cardiovascular risk, discuss ongoing vitamin D research, and consider the management of vitamin D deficiency from a cardiovascular health perspective.

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Figure 1: Human metabolism of vitamin D.
Figure 2: Cardiovascular effects of vitamin D receptor activation.
Figure 3: Dose–response association between circulating 25-hydroxyvitamin D and risk of cardiovascular disease.

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Pilz, S., Verheyen, N., Grübler, M. et al. Vitamin D and cardiovascular disease prevention. Nat Rev Cardiol 13, 404–417 (2016). https://doi.org/10.1038/nrcardio.2016.73

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