IJCS | Volume 31, Nº4, July / August 2018

DOI: 10.5935/2359-4802.20180025 422 REVIEW ARTICLE International Journal of Cardiovascular Sciences. 2018;31(4)422-432 Mailing Address: Antonio José Lagoeiro Jorge Rua Marques de Paraná, 303 - 6º andar; Postal Code: 24033-900, Centro, Niterói, RJ - Brazil. E-mail: lagoeiro@cardiol.br, lagoeiro@globo.com Vitamin D Deficiency and Cardiovascular Diseases Antonio José Lagoeiro Jorge, Jamerson Reis Cordeiro, Maria Luiza Garcia Rosa, Diego Braga Campos Bianchi Universidade Federal Fluminense, Niterói, RJ - Brazil Manuscript received May 27, 2017; revised manuscript August 21, 2017; accepted September 25, 2017. VitaminDDeficiency/physiopathology;Cardiovascular Diseases; Solar Radiation; Calcium; Phosphorus. Keywords Abstract Vitamin D is considered a steroid hormone with a broad spectrum of action in the human body. Its action arises from the binding of its active metabolite (1 α ,25- dihydroxyvitaminD) to its receptor (VDR),which ispresent throughout the body, including vascular smooth muscle cells and cardiomyocytes. Initially, vitamin D deficiency was related only to changes in themusculoskeletal system, but in recent years, researchers have demonstrated its relationship with several pathologies related to other systems, such as cardiovascular diseases. The objective of this study is to review vitamin D’s pathophysiology, describe its relationship with cardiovascular diseases based on the most recent publications, and highlight the results of vitamin supplementation in the prevention of such pathologies. Introduction Vitamin D, the fourth vitamin to be described, was initially characterized as a factor capable of curing rickets, a disease characterized by bone demineralization and skeletal deformities. 1 Currently, vitamin D comprises a group of secosteroid molecules derived from 7-dehydrocholesterol (7- DHC) that includes the active metabolite (1 α ,25- dihydroxyvitamin D or calcitriol), its precursors (cholecalciferol or vitamin D3, ergocalciferol or vitamin D2 , and 25-hydroxyvitamin D or calcidiol), as well as its degradation products. 2 These molecules, alongwith their carrier proteins and receptors, comprise an important metabolic axis: the endocrine vitamin D system. 3 The active vitamin D has a fundamental role in regulating bone and mineral physiology, in particular, calcium and phosphorus metabolism. It is also involved in the homeostasis of several other cellular processes, such as the modulation of autoimmunity and synthesis of inflammatory interleukins, 4 blood pressure control, 5 and participation in the process of cell multiplication and differentiation. 6 The spectrum of action of vitamin D is so broad that microarray studies show that 1 α ,25- dihydroxyvitamin has more than 900 potential gene targets, corresponding to approximately 3% of the human genome. 7 Epidemiological studies have found that a significant portion of the world population, regardless of age, ethnicity, and geographical location, has low serum levels of vitamin D, 8 as illustrated in Figure 1. Some countries even present rates of vitamin D deficiency above 50%, as observed in Brazil, Denmark, and Germany. Recent studies have associated inadequate serum vitamin D levels with several diseases unrelated to the musculoskeletal system, such as cancer (colon, prostate, and breast), autoimmune and inflammatory diseases (multiple sclerosis, Crohn’s disease), depression, and cardiovascular diseases (CVDs) such as hypertension, coronary artery disease (CAD), and heart failure (HF). 9 The objective of this study was to review vitamin D’s pathophysiology, describe its relationship with CVD based on the most recent publications, and highlight the results of vitamin supplementation in the prevention of such diseases. Physiology and mechanism of action In humans, only 10 to 20% of the vitamin D derives from the diet, and the remaining 80% is synthesized endogenously. 10 Few foods have significant amounts of this vitamin, of which the main ones are listed in Table 1.