In addition to possible direct effects due to the presence of the vitamin D receptor and of the 1-alpha hydroxylase enzyme in cardiac myocytes and other cells of the cardiovascular system [79], vitamin D has significant effects on several cardiovascular risk factors. Studies, ranging from animal Go6983 clinical trial studies to clinical trials, have shown that pharmacological doses of vitamin D notably reduce inflammation [80], improve endothelial function [81], control the secretion of insulin and improve insulin sensitivity [82]. Furthermore, as recently reviewed, vitamin D status has been linked to arterial hypertension [83].

Several observational studies suggest that 25(OH) vitamin D levels less than 15 ng/ml are associated with an excess risk of cardiovascular events when compared to levels >30–40 ng/ml. A nested case–control study in 18,225 men in the Health Professionals

Follow-up Study (men selleck inhibitor aged 40–75 years, free of cardiovascular disease at baseline) showed that men with a 25(OH) vitamin D level ≤15 ng/ml had an increased risk for myocardial infarction relative to men with a level ≥30 ng/ml (RR 2.42; 95% CI 1.35–3.84) [84]. Even men with a 25(OH) vitamin D level 22.6–29.9 ng/ml had an increased risk (RR 1.60; 95% CI 1.10–2.32) compared with those with a level ≥30 ng/ml. In the Framingham offspring cohort study, 25(OH) vitamin D was measured in 1,739 participants without prior heart disease. At a mean follow-up of 5.4 years, amongst those with AZD4547 datasheet hypertension, there was a 2-fold increase in the risk of cardiovascular events for the participants with a 25(OH) vitamin D level <15 ng/ml compared to those with a level ≥15 ng/ml

[34]. The Ludwigshafen Risk Ixazomib in vivo and Cardiovascular Health Study, a prospective cohort comprising 3,300 patients referred to coronary angiography and followed for 7.7 years, demonstrated a strong association between vitamin D status and several cardiovascular outcomes, such as cardiovascular mortality [85], stroke [86], heart failure and sudden cardiac death with the lowest risk amongst those with the highest 25(OH) vitamin D levels [87]. However, such associations have not been found in other studies. In the Osteoporotic Fractures in Men Study, vitamin D intake was evaluated in 3,094 men and 25(OH) vitamin D was measured in 813 men. The authors found no association between vitamin D intake or 25(OH) vitamin D levels and incidence of cardiovascular disease during a median follow-up of 4.4 years [88]. Similarly, serum levels of 25(OH) vitamin D levels were not independently associated with cardiovascular mortality in the prospective Rancho Bernardo study including 1,073 community-dwelling older adults followed up to 10.4 years [89]. On the other hand, in a cross-sectional study of 2,722 subjects, the prevalence of hypertension was found to be increased in subjects with 25(OH) vitamin D levels <40 ng/ml; odds ratios were 2.7 (1.4–5.2), 2.0 (1.4–5.2) and 1.3 (1.2–1.