Vitamin D deficiency and cardiovascular disease: the missing link

Abstract

ciated primarily with bone health, and typically, a marked deficiency causes rickets in children and osteomalacia in adults. There is a well-described association between vitamin D deficiency and muscle weakness and skeletal pain [1,2]. However, the vitamin D receptor (VDR) is expressed not only in bone but also ubiquitously in other tissues and cells, including lymphocytes, cardiomyocytes, the endothelium, pancreatic β-cells and foam cells [3,4]. Thus, vitamin D may regulate suppressor T-cell populations [5], modulating immune function, inhibiting cellular growth, stimulating insulin secretion and inhibiting renin production, providing a potential mechanistic basis for a range of common conditions such as asthma [6], Type 1 diabetes [7], multiple sclerosis [8], cancer [9] and cardiovascular disease. The focus of this article is to explore the role of vitamin D deficiency in relation to cardiovascular disease. Estimates of vitamin D deficiency in the UK suggest it may affect approximately 61–87% of adults, depending on the season [10]. Several large observational studies have linked vitamin D deficiency with cardiovascular disease [11–14]. The Framingham Offspring Study The Framingham Offspring Study is a landmark epidemiological study, which longitudinally followed up individuals (n = 1739) for a mean length of 5.4 years [12]. There was no prior history of cardiovascular disease in this cohort, and prespecified baseline 25-hydroxy vitamin D (25[OH] vitamin D) levels were used to stratify deficiency (<10ng/ml, <15 ng/ml and ≥15 ng/ml). During the follow-up period, a composite of cardiovascular events were classified as myocardial infarction, cardiac insufficiency, angina, stroke, transient ischemic attack, peripheral claudication or heart failure. After multivariate adjustment for conventional risk factors, those with 25(OH) vitamin D levels of less than 15ng/ml had a hazard ratio of 1.62 (95% CI: 1.11–2.36; p = 0.01) for incident cardiovascular events compared with those with 25(OH) vitamin D levels of 15 ng/ml or higher. This increased risk was even more evident in those with hypertension (hazard ratio: 2.13 [95% CI: 1.30–3.48]). Furthermore, there was a graded increase in cardiovascular risk across the categories with a hazard ratio of 1.53 (95% CI: 1.00–2.36) for