Looking for a Brighter Future in Heart Failure: A Role for Vitamin D Supplementation?

SEE PAGE 2593 I dentifying effective pharmacologic and mechanical therapies for heart failure has been an active and costly endeavor in the past several decades. Significant progress has been made, but the morbidity and mortality from this syndrome continues to be unacceptably high. Thus, it would be an exciting development if a relatively simple intervention such as vitamin D supplementation was shown to improve outcomes in heart failure. Vitamin D is a steroid hormone that modulates gene transcription by binding a nuclear receptor found in numerous tissues, including the heart and vasculature. One of the genes regulated by vitamin D is renin. Vitamin D acts as an endogenous inhibitor of renin expression (1). Mice with genetic deficiency of vitamin D activity, from loss of either the vitamin D receptor or the 1-alpha-hydroxylase enzyme (which converts 25-hydroxyvitamin D to activated vitamin D), develop hypertension and ventricular hypertrophy (2–4). In the 1-alpha-hydroxylase knockout mice, direct administration of activated vitamin D rescues the phenotype and normalizes left ventricular mass (4). Furthermore, administration of vitamin D analogs to Dahl salt-sensitive rats reduces the degree of left ventricular hypertrophy (5). Vitamin D analogs improve not only left ventricular structure, but also functional parameters of contractility and relaxation (5,6). Pre-clinical data suggest that