Vitamin D: Cardiovascular Effects and Vascular Calcification

Vitamin D plays a biphasic role in human health, with both intoxication and insufficiency compromising cardiovascular physiology. Dynamic interactions between the parathyroids, kidneys, and bone determine the toxicity threshold for vitamin D and calcium—i.e., whether hypervitaminosis D or excessive calcium intake is associated with cardiovascular toxicity. Age-dependent decline in renal function afflicts ~25% of our population over age 60, and awareness of chronic renal insufficiency is very poor. Because vitamin D toxicities relate in part to abnormal serum and vascular calcium phosphate homeostasis recommended daily intakes of vitamin D and vitamin D agonist (vitamin D receptor (VDR) agonists, VDRAs) treatment should incorporate consideration of the common “renal frailty” of aging. Conversely, vitamin D insufficiency is associated with significant, undesirable changes in cardiovascular physiology and structure. As vasculotropic hormones, VDRAs have clear therapeutic roles in the setting of end-stage renal disease (ESRD); benefits relate in part to VDRA-mediated improvements in endothelial function via antiinflammatory actions, mitigation of the untoward cardiometabolic consequences of severe secondary hyperparathyroidism, and reductions in myocardial hypertrophic responses. Importantly, detailed physiological assessment of cardiovascular function has newly identified improvements in myocardial performance with vitamin D supplementation in patients with heart failure However, data demonstrating clinically significant cardiovascular benefit of vitamin D supplementation and/or VDRAs in individuals without ESRD are just as meager in 2016 as they were 2010. Much work remains to be done with respect to vitamin D and cardiometabolic physiology, but assiduous attention to the lessons learned hold tremendous promise to benefit human health and healthcare in our aging societies.