Vitamin D Repletion in Coronary Artery Disease
Vitamin D Repletion in Coronary Artery Disease
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.
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