vitamin d repletion in coronary artery disease

Conditions: Vitamin D Deficiency; Coronary Artery Disease; Endothelial Dysfunction; Inflammation

Summary: vitamin d (vit d) status is an emerging risk marker of great interest in cardiovascular disease (cvd). lower serum levels of vit d are associated with both cardiac risk factors and prevalent cardiovascular disease. vit d insufficiency remains very prevalent in free living populations in the united states especially in urban, and multi-ethnic low income northern cities.to date, prospective randomized trials using vit d supplementation to modify cvd risk and evaluate outcomes have not been performed. the investigators propose a double-blind, randomized wait-list control trial in subjects with coronary artery disease (cad) and vit d deficiency with two specific aims. specific aim 1 is to measure endothelial function using reactive hyperemia peripheral arterial tonometry (rh-pat) before and after treatment with vit d replacement therapy. specific aim 2 is to measure levels of inflammation before and after treatment with vit d replacement therapy. these aims will test the hypotheses that vit d repletion will improve endothelial function and reduce the levels of detectable inflammation in the plasma of these subjects.

100 subjects with angiographically documented cad and vit d deficiency will be randomized to 50,000 iu oral ergocalciferol (active treatment group) or placebo (delayed intervention group) once a week for 12 weeks. the investigators will measure endothelial function at randomization and week 12 using rh-pat and serologically measured adhesion molecules (s-vcam, s-icam, soluble e-selectin). changes in levels of plasma cytokines and chemokines representing a t-cell activation pathway (il-12, ifn-g and cxcl-10 - "ifn-g axis") the investigators have linked to coronary atherogenesis (independent of crp) and poor cv outcomes, will be measured over the 12 week study period. given published evidence showing that vit d can influence this t- cell pathway, specific aim 2 will add mechanistic insights to this proposal. high sensitivity c-reactive protein (hs-crp) will be measured as it is a well established traditional marker of inflammation in cad and has also been linked to vit d status.

Eligibility criteria:
inclusion criteria: * male and nonpregnant females greater than 18 years of age * ≥ 50% angiographic stenosis of at least 1 coronary artery or documented previous revascularization * serum 25-hydroxyvitamin d \< 20 ng/ml exclusion criteria: * confinement to a nursing facility, institution or home * gfr \< 60 ml/min (by mdrd equation) * presence of liver disease * hypercalcemia * nyha class iii or iv heart failure * cardiogenic shock at time of presentation * current planned or emergent cabg * prior gastric or small bowel surgery * pancreatitis * malabsorption * inflammatory bowel disease * autoimmune disease * active malignancy * current use of \> 800 iu/day of vitamin d * current use of dilantin, phenobarbitol, immunosuppressant, or immunostimulant therapy

Keywords: vitamin d, vitamin d deficiency coronary artery disease ergocalciferol endothelial function adhesion molecules inflammation il-12 interferon-gamma cxcl-10 reactive hyperemia peripheral arterial tonometry endothelial dysfunction cytokines chemokines