Vitamin D insufficiency may be associated with increased risk of coronary heart disease (CHD) and cardiovascular disease (CVD) in general, but uncertainties exist beyond published reports. Our systematic review of published prospective studies of serum levels of 25-hydroxyvitamin D [25(OH)D] suggests the possibility of an important association with CVD. The exact biological pathways that could link vitamin D and CHD remain unclear, but there is evidence that vitamin D insufficiency impairs pancreatic ß-cell function and promotes insulin resistance, either directly (by vitamin D receptor activation) or indirectly (by calcium homeostasis regulation), perhaps mediated by high blood pressure, hyperinsulinaemia, hyperglycaemia, diabetes, and dyslipidaemia. The potential role of vitamin D’s active metabolite 1,25(OH)2D in regulating cellular functions through the vitamin D receptor has been described for a list of several target genes, including renin, insulin, and different cytokines, which are orchestrated in a cell-specific manner. Vitamin D receptors are present in vascular smooth muscle cells, endothelial cells, and cardiomyocytes. Vitamin D regulates the renin-angiotensin system, suppresses proliferation of vascular cell smooth muscle, and improves insulin resistance.
The Vitamin D Studies Collaboration (VitDSC) aims to conduct meta-analysis of individual participant data to address uncertainties in the epidemiological evidence thus far on the association of circulating 25(OH)D and cardiovascular disease, including:
1. Assessment of the shape of dose-response relationships.
2. Consistently adjusting for possible confounding factors (eg, season, age, sex, obesity, smoking, etc).
3. Correcting associations for regression dilution in both 25(OH)D levels and in the confounders.
4. Evaluating whether the association of 25(OH)D and CVD risk differs importantly by clinically relevant subgroups (eg, by age, sex, smoking, diabetes, ethnicity, and other established risk factors).
5. Assessment of the cross-sectional correlates of 25(OH)D levels.
The primary outcome will be first-onset CHD (defined as first-ever non-fatal MI or CHD death) with subsidiary analyses of stroke, composite cardiovascular endpoint, non-vascular outcomes, and all-cause mortality.
Vitamin D Studies Collaboration Coordinating Centre
Department of Public Health & Primary Care
University of Cambridge
Strangeways Research Laboratory
Cambridge, CB1 8RN, UK
Tel: +44 (0)1223 741302
Fax: +44 (0)1223 741339