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). 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.

Vitamin D deficiency in postmenopausal, healthy women predicts increased cardiovascular events: a 16-year follow-up study

“…In 554 healthy subjects, 25(OH)D correlated with vascular function in subjects without traditional risk factors as well as in subjects with a number of risk factors, after adjusting for several confounders. Moreover, in subjects, that corrected vitamin D insufficiency an improvement in vascular function was seen (35). In a randomised trial, vitamin D supplements reduced arterial stiffness (36).…”

Association between serum vitamin D levels and subclinical coronary atherosclerosis and plaque burden/composition in young adult population

“…Vascular smooth muscle cells and endothelial cells express receptors for 25(OH)D and could convert 25-hydroxyvitamin D3, the major circulating metabolite of vitamin D3, to 1,25-dihydroxyvitamin D3 (1,25(OH)2D) [21]. In addition, Al Mheid et al [22] reported that 25(OH)D insuffi ciency was associated with increased arterial stiff ness and endothelial dysfunction in a community-based asymptomatic population. Another mechanism may be pancreatic β-cell dysfunction, peripheral tissue resistance to insulin predisposing to diabetes [23], and activation of the renin-angiotensin system predisposing to hypertension [24].…”

Effects of a Health‐Partner Intervention on Cardiovascular Risk

“…Around 30% of solicited employees agreed to be contacted for screening, and ≈10% were ultimately enrolled in the cohort 14. Subjects with an acute illness, recent hospitalization within the past year, pregnant women, and individuals with poorly controlled medical conditions were excluded, and subjects signed an informed consent that was approved by the Emory and Georgia Tech institutional review boards 15, 16…”