Vitamin D and Cardiovascular Disease

Abstract

Vitamin D (nutritional term for compounds with biological activity of 1α,25-dihydroxyvitamin D; also used to indicate summation of Vitamin D 2 and D 3 ) is a fat-soluble vitamin that functions as a steroid hormone. It plays a crucial role in mineral homeostasis and skeletal health and its deficiency classically leads to rickets in children and osteomalacia in adults. 1 Its primary action on the skeletal system is to regulate calcium and phosphorus metabolism by influencing intestinal absorption, bone resorption, and renal retention (Figure 1). Vitamin D metabolites also play an integral physiological role in nonskeletal tissues and have been implicated in a wide range of chronic pathology, including skin and autoimmune disease, cancer, diabetes mellitus, hypertension, and cardiovascular disease (CVD).2 Interest in the role of vitamin D in CVD arose from evidence of adverse cardiovascular effects of vitamin D deficiency in animal models, 3 and epidemiological studies reporting the increase in cardiovascular events in winter and at increasing distance from the equator. Various extrarenal tissues, including many cell types involved in CVD, also express CYP27B1 and are therefore able to produce 1,25(OH) 2 D. This local production and breakdown is not subject to the same feedback controls as renal production. Vitamin D Deficiency and ExcessThere is controversy about the definition of vitamin D deficiency (or hypovitaminosis D), the optimum serum level of 25(OH)D, and the dietary requirements of vitamin D.

Ergocalciferol Supplementation in Hemodialysis Patients With Vitamin D Deficiency: A Randomized Clinical Trial

“…Vitamin D receptors are present within the vasculature and heart, and vitamin D deficiency has been implicated in the pathogenesis of left ventricular hypertrophy, cardiac fibrosis, endothelial dysfunction, and renin-angiotensin system activation. 40 We found no change in BP in the present study, consistent with a 6-month trial of cholecalciferol at a dose of 3000 IU daily versus placebo in 64 patients on hemodialysis, which also found no effect on arterial stiffness or cardiac structure or function. 23 Evidence for reduction in CV events with nutritional vitamin D in the general population is lacking.…”

Is fibroblast growth factor 23 a new cardiovascular risk marker in gestational diabetes?

“…1,25(OH) 2 D 3 is the primary regulator of FGF23 production via osteoblasts in bone, and increased FGF23 levels cause a reduction in 1,25(OH)2D3 levels (21). The decrease in 1,25(OH) 2 D 3 can cause elevated angiotensin II production via an increase in renin expression, which results in hypertension and cardiac hypertrophy (22)(23)(24). The decrease in vitamin D levels is associated with adverse outcomes in the general population (25).…”

Matrix metalloproteinase-10 and microvascular complications of type 1 diabetes: might vitamin D status be relevant?

“…In a recent issue of Diabetologia, Toni et al [2] report increased circulating MMP-10 in association with increased microvascular disease risks in type 1 diabetes; this finding is in line with the earlier observations, and, as the authors suggest, provides a potential therapeutic target for reducing microvascular disease risks. Vitamin D repletion is associated with reductions in macrovascular disease risks and, although causation remains unproven, plausible mechanisms exist [3]. Increased circulating MMP-9, inversely correlated with severity of vitamin D insufficiency, was reduced by ∼70% in response to modest improvement in vitamin D repletion in healthy South Asians [4], and circulating MMP-9 increased with reduction in vitamin D status in submariners after an 85 day submerged patrol [5].…”