Conditions: Vitamin D Deficiency Coronary Artery Disease Endothelial Dysfunction Inflammation
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
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 96
Healthy volunteers: no

Brief 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.

Detailed description:
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.

Arms:
arm 1: 50,000 units of ergocalciferol once a week for 12 weeks arm 2: None

Interventions: intervention 1: Ergocalciferol intervention 2: Sugar pill
Intervention descriptions: intervention 1: Oral capsule, 50,000 units, once a week, 12 weeks intervention 2: Oral capsule, once a week, 12 weeks

Protocol document: