Vitamin D and the Cardiovascular System

Several epidemiologic and clinical studies have suggested that there is a strong association between hypovitaminosis D and cardiovascular disease (CVD). Hypovitaminosis D was reported as a risk factor for increased cardiovascular events among 1739 adult participants in the Framingham Offspring Study. Analysis of more than 13,000 adults in the Third National Health and Nutrition Examination Survey (NHANES III) showed that even though hypovitaminosis D is associated with an increased prevalence of CVD risk factors, its association with all-cause mortality is independent of these risk factors. Importantly, epidemiologic studies suggested that patients who had chronic kidney disease and were treated with activated vitamin D had a survival advantage when compared with those who did not receive treatment with these agents. Mechanistically, emerging data have linked vitamin D administration with improved cardiac function and reduced proteinuria, and hypovitaminosis D is associated with obesity, insulin resistance, and systemic inflammation. Preliminary studies suggested that activated vitamin D inhibits the proliferation of cardiomyoblasts by promoting cell-cycle arrest and enhances the formation of cardiomyotubes without inducing apoptosis. Activated vitamin D has also been shown to attenuate left ventricular dysfunction in animal models and humans. In summary, emerging studies suggest that hypovitaminosis D has emerged as an independent risk factor for all-cause and cardiovascular mortality, reinforcing its importance as a public health problem. There is a need to advance our understanding of the biologic pathways through which vitamin D affects cardiovascular health and to conduct prospective clinical interventions to define precisely the cardioprotective effects of nutritional vitamin D repletion. Clin J Am Soc Nephrol 4: 1515-1522, 2009. doi: 10.2215/CJN.02260409