Vitamin D Repletion in Coronary Artery Disease

Not Applicable

Completed

Conditions: Vitamin D Deficiency
Coronary Artery Disease
Endothelial Dysfunction
Inflammation

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Ergocalciferol	Ergocalciferol	50,000 units of ergocalciferol once a week for 12 weeks
Sugar pill	Sugar pill	-

Primary Outcome Measures

Name	Time	Method
Inflammation -	Baseline and 12 weeks	Median within subject change in hs-CRP levels between baseline and week 12 in active and placebo groups
Inflammation	Baseline to week 12	Median within subject change in IL-12 levels between baseline and week 12 in active and placebo groups
Endothelial Function	Baseline and 12 weeks	Endothelial function was measured using peripheral arterial tonometry expressed as the reactive hyperemia index. The index is derived from the ratio of the post-to-pre occlusion peripheral arterial tonometry signal amplitude of the tested arm, divided by the post -to-pre occlusion ratio of the control arm. Median within subject change in endothelial function as measured by reactive hyperemia peripheral arterial tonometry index in each group is presented.

Secondary Outcome Measures

Name	Time	Method

Locations (2): Montefiore Medical Center / Weiler division
🇺🇸
Bronx, New York, United States
Jacobi Medical Center
🇺🇸
Bronx, New York, United States