Can Vitamin D Deficiency Impact Cardiovascular Health in the Elderly?

Abstract

Life expectancy is increasing worldwide. Nevertheless, the burden of cardiovascular disease (CVD) morbidity and mortality is still high in developed countries and is rapidly increasing in developing countries [1]. During the last decade, it also became clear that insufficient and even deficient vitamin D status is a worldwide problem [2]. By far the most important reason for this phenomenon is an inadequate skin exposure to solar ultraviolet B radiation, since ultraviolet B-induced skin synthesis is the major source of vitamin D for humans. It has long been known that vitamin D plays a major role in bone mineral homeostasis by promoting the transport of calcium and phosphate to ensure adequate blood levels of these ions for normal bone mineralization. Bone diseases such as rickets and osteomalacia are well-known consequences of vitamin D deficiency in infants and adults, respectively. However, is there any rationale to assume that vitamin D deficiency might be a causal factor of CVD-related morbidity and mortality? In the last several decades, many studies have documented nontraditional roles of vitamin D, including immunomodulatory properties and the regulation of intracellular calcium concentrations. Receptors for the active form of vitamin D, 1,25-dihydroxyvitamin D, have been found in almost all human tissues and cells. Therefore, vitamin D is now regarded as an important protective factor for cellular health. Circulating levels and cellular availability of 1,25-dihydroxyvitamin D directly depend on blood concentrations of its precursor 25-hydroxyvitamin D (25[OH]D). Serum 25(OH)D is the hallmark for determining vitamin D status. Cut-offs are below 25 nmol/l for deficiency, 25–49.9 nmol/l for insufficiency, 50–74.9 nmol/l for borderline status and 75 nmol/l or greater for normal status. There is now increasing evidence that 1,25-dihydroxyvitamin D exerts important physiological actions in the vasculature. These mechanisms include the inhibition of vascular smooth muscle proliferation, the suppression of vascular calcification, the downregulation of proinflammatory cytokines, the upregulation of anti-inflammatory cytokines and the action of vitamin D as a negative endocrine regulator of the renin–angiotensin system. Studies in knockout mice have confirmed that the absence of vitamin D-receptor activation leads to hypertension, left ventricular hypertrophy and disturbed blood coagulation. Ecological studies have reported higher rates of coronary heart diseases and hypertension with increasing distance from the equator, a phenomenon that could be attributed to the higher prevalence of vitamin D deficiency in regions with less exposure to sunlight [3]. In addition, clinical studies have reported cross-sectional associations between lower vitamin D levels and prevalent cardiovascular disease. The most important results come from a recently published prospective longitudinal study demonstrating that individuals with 25(OH)D levels below 37.5 nmol/l had a multivariable-adjusted hazard ratio of 1.62 for incident cardiovascular events compared with those with 25(OH)D levels of 37.5 nmol/l or greater [4].