Abstract 15592: Increased Circulating Progenitor Cells in Women With Microvascular Coronary Dysfunction: Results From the NHLBI-Sponsored Women’s Ischemia Syndrome Evaluation - Coronary Vascular Dysfunction Study (WISE-CVD)
Background: Women with ischemia but no obstructive CAD often have microvascular coronary dysfunction (MCD). Ischemia stimulates a reparative response resulting in mobilization of progenitor cells (PCs), but PCs in subjects with vascular disease may not have the capacity to proliferate. Preliminary studies show that PC colonies in culture are reduced in MCD. We hypothesized that women with ischemia from MCD will mobilize PCs into the circulation.
Methods: In 160 women with ischemia but no obstructive CAD enrolled in the WISE study, we measured intracoronary adenosine-mediated coronary flow reserve (CFR) (n=160), acetylcholine-mediated microvascular endothelial function (n=48), and nitroglycerin-mediated endothelium-independent function (n=49). Circulating PC counts were measured using flow cytometry for expression of CD34, CD133, and CXCR4 epitopes on CD45med mononuclear cells.
Results: Subjects were 53±11 years, BMI of 30±9; 38% were hypertensive, 10% diabetic, 28% hyperlipidemic, and 7% smokers. Lower CFR with adenosine correlated with higher circulating levels of CD34+ (r= -0.19, p=0.015) and CD34+/CD133+ (r= -0.18, p=0.020). Lower vasodilation with acetylcholine correlated with higher CD34+/CD133+ cells (r= -0.29, p=0.044). In multivariate analyses, after adjusting for the aforementioned covariates, lower CFR remained significantly associated with elevated levels of CD34+ (p=0.020), CD34+/CD133+ (p=0.029) and CD34+/CXCR4+ (p=0.046) cells. Moreover, lower acetylcholine responses remained independently associated with higher levels of CD34+ (p=0.048), CD34+/CD133+ (p=0.031), and CD34+/CXCR4+ (p=0.018) cells. CPC levels did not correlate with nitroglycerin responses.
Conclusion: In women with MCD, reduced microvascular endothelial function and impaired CFR are associated with mobilization of PCs, suggesting that vascular dysfunction and/or ischemia stimulate PC mobilization. Whether impaired mobilization despite ischemia is associated with adverse outcomes in this population, as observed in patients with CAD, needs further investigation.
- © 2013 by American Heart Association, Inc.