Vitamin D Status Is Associated With Arterial Stiffness and Vascular Dysfunction in Healthy Humans

• Type of Material: Article
• Authors: Ibhar Al Mheid, Emory University; Riyaz Patel, Emory University; Jonathan Richard Murrow, Emory University; Alanna A. Morris, Emory University; Ayaz M. Rahman, Emory University; Lucy Fike, Emory University; Nino Kavtaradze, Emory University; Irina Uphoff, Emory University; Craig Hooper, Centers for Disease Control and Prevention; Vin Tangpricha, Atlanta VA Medical Center; R Wayne Alexander, Emory University; Kenneth L Brigham, Emory University; Arshed Ali Quyyumi, Emory University
• Language: English
• Date: 2011-07-05
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2011 by the American College of Cardiology Foundation
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jacc.2011.02.051
• Title of Journal or Parent Work: Journal of the American College of Cardiology
• ISSN: 0735-1097
• Volume: 58
• Issue: 2
• Start Page: 186
• End Page: 192
• Grant/Funding Information: This study was supported by the American Heart Association, The Emory Predictive Health Institute, Woodruff Fund, and in part by National Institutes of Health Grants UL1RR025008 from the Clinical and Translational Science Award program and M01RR0039.
• Keywords: endothelial function; arterial stiffness; vitamin D
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

Objectives The primary objective of this study was to elucidate mechanisms underlying the link between vitamin D status and cardiovascular disease by exploring the relationship between 25-hydroxyvitamin D (25-OH D), an established marker of vitamin D status, and vascular function in healthy adults. Background Mechanisms underlying vitamin D deficiency-mediated increased risk of cardiovascular disease remain unknown. Vitamin D influences endothelial and smooth muscle cell function, mediates inflammation, and modulates the renin-angiotensin-aldosterone axis. We investigated the relationship between vitamin D status and vascular function in humans, with the hypothesis that vitamin D insufficiency will be associated with increased arterial stiffness and abnormal vascular function. Methods We measured serum 25-OH D in 554 subjects. Endothelial function was assessed as brachial artery flow-mediated dilation, and microvascular function was assessed as digital reactive hyperemia index. Carotid-femoral pulse wave velocity and radial tonometry-derived central augmentation index and subendocardial viability ratio were measured to assess arterial stiffness. Results Mean 25-OH D was 31.8 ± 14 ng/ml. After adjustment for age, sex, race, body mass index, total cholesterol, low-density lipoprotein, triglycerides, C-reactive protein, and medication use, 25-OH D remained independently associated with flow-mediated vasodilation (β = 0.1, p = 0.03), reactive hyperemia index (β = 0.23, p < 0.001), pulse wave velocity (β = −0.09, p = 0.04), augmentation index (β = −0.11, p = 0.03), and subendocardial viability ratio (β = 0.18, p = 0.001). In 42 subjects with vitamin D insufficiency, normalization of 25-OH D at 6 months was associated with increases in reactive hyperemia index (0.38 ± 0.14, p = 0.009) and subendocardial viability ratio (7.7 ± 3.1, p = 0.04), and a decrease in mean arterial pressure (4.6 ± 2.3 mm Hg, p = 0.02). Conclusions Vitamin D insufficiency is associated with increased arterial stiffness and endothelial dysfunction in the conductance and resistance blood vessels in humans, irrespective of traditional risk burden. Our findings provide impetus for larger trials to assess the effects of vitamin D therapy in cardiovascular disease.