Abstract 20380: CD34+ Cell Number and Function Predicts Coronary Flow Reserve and is a Potential Biomarker for Microvascular Coronary Artery Disease
Introduction: Standard risk stratification schemes underestimate the risk of cardiovascular events in women. However we have shown in the WISE study that coronary microvascular dysfunction (MCD) is the best independent predictor of cardiovascular events over 5.4 years, among women with symptoms suggesting ischemia and non-obstructive coronary angiograms. Since coronary microvascular tone is regulated in part by the endothelium, it has been suggested that endothelial dysfunction might have a role in the pathogenesis of MCD. Potential progenitor cells, identified by CD34 expression and circulating endothelial cells (CEC), represent the potential to carry-out endothelial repair and the degree of endothelial injury, respectively. These cell populations may serve as indicators of vascular health.
Hypothesis: We hypothesized that number and function of circulating progenitor or mature endothelial cells could serve as biomarkers for decreased coronary flow reserve (CFR) and microvascular dysfunction.
Methods: We enrolled 32 women who were part of the WISE study, who had angina and no obstructive coronary artery disease. Coronary flow reserve was determined as an index of coronary microvascular dysfunction. CD34+ cell numbers were enumerated using FACS. CD34+ cell function was assessed by assaying migration of CD34+ cells towards SDF-1 using a Boyden chamber and by measuring bioavailable Nitric Oxide (NO). CECs were identified by monoclonal antibody to CD146.
Results: Patients with MCD had lower numbers of CD34+ cells compared to healthy controls. CD34+ cells from women with coronary flow reserve ≤ 2.5 also exhibited significant positive correlation with migration towards SDF-1 (rho=0.47 p =0.05). This significance was lost in multivariate analysis controlling for diabetes, hyperlipidemia and smoking possibly because these variables have a collinear relationship with CD34+ cell function.
Conclusions: CD34+ cell numbers are decreased in women with microvascular coronary dysfunction. CD 34+ function as evidenced by migration of CD34+ cells towards SDF is increased in women with reduced CFR. Thus circulating cells may provide mechanistic insights into coronary microvascular dysfunction (MCD) in women.
- © 2010 by American Heart Association, Inc.