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

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).

Arterial stiffness and 25-hydroxyvitamin D levels in chronic kidney disease patients

“…[13][14][15][16]30,31 Brachial-ankle PWV was found to be significantly lower in CKD patients with 25(OH)D deficiency. 15 It has been reported that flow-mediated dilatation as a marker of endothelial function was lower in vitamin D deficiency in patients with CKD, and improved with replacement of 25(OH)D. In addition, vitamin D supplementation significantly reduced biomarkers of endothelial dysfunction such as intracellular adhesion molecule (ICAM), vascular adhesion molecule (VCAM), endothelial leukocyte adhesion molecule (E-Selectin) and von Willebrand factor (vWF).…”

“…All these pathological processes result in decreased vascular compliance, increased vascular calcification and inflammation, which may contribute to the development of arterial stiffnesss. 3,15,16,27 Vitamin D deficiency is associated with cardiovascular disease, all-cause mortality, morbidity, poor clinical outcomes and rapid decline of eGFR in patients with CKD. 25,34,35 Our study has some limitations.…”

“…[13][14][15] Pulse wave velocity (PWV) and augmentation index normalized with 75/min heart rate (Alx@75) are considered to be gold standard index for arterial stiffness. 1,3,6 Al Mheid et al 16 demonstrated that 25(OH)D levels negatively correlated with PWV and Alx in healthy subjects, and reported that vitamin D deficiency increased arterial stiffness effecting by vascular dysfunction.…”

Vitamin D and risk of CVD: a review of the evidence

“…A couple of cross-sectional studies in healthy adults show lower serum levels of 25(OH)D to be associated with endothelial dysfunction (91,92) . A few trials show an improvement in flow-mediated dilation with vitamin D supplementation (93)(94)(95) , but most show no effect (79,(96)(97)(98) ( Table 2).…”

“…Many cross-sectional studies have shown inverse associations between vitamin D and arterial stiffness (91,(101)(102)(103)(104)(105)(106)(107) , but there are relatively few clinical trials that have investigated the effect of vitamin D supplementation (Table 2). Gepner et al conducted a study in which healthy postmenopausal women were randomised to 62·5 μg vitamin D 3 daily (n 57) or placebo (n 57) for 4 months.…”