Vitamin D and the Cardiovascular System

Abstract

Several epidemiologic and clinical studies have suggested that there is a strong association between hypovitaminosis D and cardiovascular disease (CVD). Hypovitaminosis D was reported as a risk factor for increased cardiovascular events among 1739 adult participants in the Framingham Offspring Study. Analysis of more than 13,000 adults in the Third National Health and Nutrition Examination Survey (NHANES III) showed that even though hypovitaminosis D is associated with an increased prevalence of CVD risk factors, its association with all-cause mortality is independent of these risk factors. Importantly, epidemiologic studies suggested that patients who had chronic kidney disease and were treated with activated vitamin D had a survival advantage when compared with those who did not receive treatment with these agents. Mechanistically, emerging data have linked vitamin D administration with improved cardiac function and reduced proteinuria, and hypovitaminosis D is associated with obesity, insulin resistance, and systemic inflammation. Preliminary studies suggested that activated vitamin D inhibits the proliferation of cardiomyoblasts by promoting cell-cycle arrest and enhances the formation of cardiomyotubes without inducing apoptosis. Activated vitamin D has also been shown to attenuate left ventricular dysfunction in animal models and humans. In summary, emerging studies suggest that hypovitaminosis D has emerged as an independent risk factor for all-cause and cardiovascular mortality, reinforcing its importance as a public health problem. There is a need to advance our understanding of the biologic pathways through which vitamin D affects cardiovascular health and to conduct prospective clinical interventions to define precisely the cardioprotective effects of nutritional vitamin D repletion. There is increasing evidence that the kidney is not unique in its ability to convert 25(OH)D to 1,25(OH)D, It was recently demonstrated that many tissues not only express the VDR but also possess 25(OH)D-1␣-hydroxylase activity. The role of this paracrine production of 1,25(OH)D in these tissues is not well understood, but a variety of in vitro studies indicated that this process may be involved in a wide range of physiologic functions, including regulation of cytokines, inflammatory and/or fibrotic pathways, the renin-angiotensin system, vascular and cardiac cell function, immune response modulation, cell growth and differentiation, and others (7-15). Several of the biologic pathways through which the effects of 1,25(OH)D are mediated remain poorly understood but may account for its role in cardiovascular health (Figure 1).

Association of Parathyroid Hormone and 25-OH-Vitamin D Levels with Arterial Stiffness in Postmenopausal Women with Vitamin D Insufficiency

“…A prospective association between reduced levels of 25-OH-vitamin D and cardiovascular risk has been observed 23,24) ; however, in a study of African Americans with type 2 diabetes mellitus, 25-OH-vitamin D levels correlated with increased calcified plaque in the aorta and carotids 52) . Thus, concern has been expressed that vitamin D could potentially accelerate vascular disease.…”

“…Vitamin D insufficiency (25-OH-vitamin D ＜30 ng/mL) 20) is relatively common in postmenopausal women 21,22) , and recent studies have suggested an association between reduced levels of vitamin D and cardiovascular risk 23,24) . Multiple mechanisms have been proposed to explain the deleterious role of hypovitaminosis D on cardiovascular risk 24) , including the negative correlation between serum vitamin D levels and arterial stiffness 25,26) .…”

“…Multiple mechanisms have been proposed to explain the deleterious role of hypovitaminosis D on cardiovascular risk 24) , including the negative correlation between serum vitamin D levels and arterial stiffness 25,26) . London et al 25) found that 25-OH-vitamin D levels were negatively correlated with aPWV in patients with end-stage renal disease.…”

Serum 25-Hydroxy Vitamin D Levels in Patients with Acute Hepatitis (Ischemic, Toxic, and Viral): Association With Clinical Progression and Mortality

“…Epidemiologic data demonstrated that the rate of diseases such as coronary heart disease, hypertension, and diabetes increase as we move away from the equatorial region, which is related to vitamin D or the lack of it. Low serum vitamin D levels were observed in patients with myocardial infarction, stroke, heart failure, diabetic cardiovascular disease, and peripheral arterial disease (11)(12)(13). Therefore, low vitamin D levels could affect as a reason or a result for acute liver injuries.…”

Mean Platelet Volume and Vitamin D Deficiency

“…In another recent comprehensive study, vitamin D deficiency is reported to be associated with hypertension, high blood glucose, cardiovascular diseases and metabolic syndrome (2). Again, in a study by Wang et al (3) it has been reported that in the cases in which the serum 25-hydroxy vitamin D (25-OHD) level was lower than 15 ng/mL, the risk for initial onset of cardiovascular system problem was found to be higher (at least two-fold) than the control group (serum 25-OHD >15 ng/mL).…”