Abstract 15627: Identification of Cardiovascular Risk Factors Associated With Bone Marrow Cell Subsets in Patients With STEMI: A Biorepository Evaluation From the CCTRN TIME and LateTIME Clinical Trials
Objective: Results from several randomized, controlled cell therapy trials suggest that the use of autologous bone marrow mononuclear cells (BMMNCs) results in only modest benefits in patients with ST-segment elevation myocardial infarction (STEMI). However, the patients in these trials had varying combinations of underlying cardiovascular risk factors (CVRFs) and comorbidities. The autologous BMMNC product administered to each patient was unique. Based on our previous findings, the purpose of this study was to identify potential associations between specific CVRFs and BMMNC subsets in patients with STEMI.
Methods: This study evaluated a cohort of patients with STEMI who were enrolled in either the CCTRN TIME or LateTIME trials and underwent BMMNC or placebo treatment (N=139). Flow cytometric analysis targeting phenotypic markers (eg, CD45, CD14, CD11b, CD3, CD19, CD31, and CD34) was used to assess the frequency of BMMNC subsets at baseline. The GRACE ACS Risk Score 2.0 - 3 year death (GRS) was used to stratify patients according to cardiovascular risk (low: GRS <12%, moderate: GRS 12-30%, high: GRS >30%). Multivariable models were then applied to assess relationships between BMMNC subsets and CVRFs, including age, smoking, hypertension, hyperlipidemia, and sex.
Results: Patients were grouped as low GRS (n=69, 49.6%), moderate GRS (n=49, 35.3%), and high GRS (n=21, 15.1%). Patients with a high GRS had significantly lower frequencies of CD45+CD31+ cells than those with a low GRS (35.6% vs 40.3%, respectively, P=0.041). In multivariable analyses, age was inversely associated with the frequencies of CD34+ (P=0.011) and CD45+CD31+ (P=0.001) cells, and smoking was associated with a decrease in CD45+CD31+ cells (P=0.022). In addition, higher frequencies of CD11b+ cells were associated with hypertension (P=0.010) and hyperlipidemia (P=0.029). In contrast, the CD11b+ cell frequency was less in females (P=0.005).
Conclusions: This study identified associations between specific CVRFs and BMMNC subsets. These associations may contribute to the heterogeneity of the cell product received. Thus, differences in patients’ comorbidities should be considered when designing future autologous cell therapy trials.
Author Disclosures: A. Contreras: None. A.F. Orozco: None. R.C. Schutt: None. M.M. Resende: None. L. Sampaio: None. J.P. Cooke: None. A. Bhatnagar: None. R. Bolli: None. M. Cohen: None. J.T. Willerson: None. L. Moyé: None. D.A. Taylor: None.
- © 2015 by American Heart Association, Inc.