Abstract 17150: Hematopoietic Progenitor Cells Expressing CD34+ and CD133+ Surface Markers are Predictors of Adverse Cardiovascular Outcomes in a Population with Coronary Artery Disease
Background: Circulating progenitor cell (PCs) levels may reflect intrinsic regenerative/ reparative potential. We hypothesized that that low levels of early PC sub-populations will be associated with worse long term outcomes.
Methods: In 479 participants enrolled in the Emory Cardiovascular Biobank (mean age 62.5, male 64%), we performed an initial exploratory study (Group 1) using flow cytometry to quantify mononuclear cells expressing CD34, 133 and VEGF2R surface markers followed by a validation study in another 414 participants (Group 2, mean age 63.0, male 66%), where CXCR4 expression was also additionally measured. Cell counts were categorized as high or low by ROC analysis. All participants were followed for the composite endpoint of CV death/MI.
Results: Lower CD34 counts correlated with advanced age (p<0.001) and female gender (p<0.01), but not with other traditional risk factors or acute MI. Low CD34+ and CD34+/133+ cell counts but not VEGF2R+ subgroups predicted adverse outcomes after a median follow-up of 1.4 years (Table 1). This finding was validated in the replication cohort, followed for 1.1 years (Table 1). In the combined cohort (n=893), subjects with low CD34+ and CD34+/133+ subsets had a HR of 2.34 and 2.90 respectively for CV death/MI compared to those with high counts, independent of covariates including CAD and acute MI at baseline. Finally, co-expression of CXCR4 on CD34+/133+ cells was also associated with adverse outcomes (HR 3.07), independent of the aforementioned covariates.
Conclusion: The PC population characterized by CD34/133 cells is reproducibly associated with adverse outcomes in a heterogeneous population with coronary heart disease. In addition circulating PCs that express CXCR4, and are capable of homing, may represent a population enriched for stem cells involved in repair and regeneration.
- © 2012 by American Heart Association, Inc.