CD14++CD16+ monocytes independently predict cardiovascular events: a cohort study of 951 patients referred for elective coronary angiography
Kyrill S Rogacev, Bodo Cremers, Adam M Zawada, Sarah Seiler, Nadine Binder, Philipp Ege, Gunnar Große-Dunker, Isabel Heisel, Florian Hornof, Jana Jeken, Niko M Rebling, Christof Ulrich, Bruno Scheller, Michael Böhm, Danilo Fliser, Gunnar H Heine, Kyrill S Rogacev, Bodo Cremers, Adam M Zawada, Sarah Seiler, Nadine Binder, Philipp Ege, Gunnar Große-Dunker, Isabel Heisel, Florian Hornof, Jana Jeken, Niko M Rebling, Christof Ulrich, Bruno Scheller, Michael Böhm, Danilo Fliser, Gunnar H Heine
Abstract
Objectives: The aim of this study was to analyze the yet ill-defined relationship of distinct human monocyte subsets with cardiovascular outcomes in a broad patient population at cardiovascular risk.
Background: Monocytes, the most abundant immune cell type found in atherosclerotic plaques, are crucial promoters of atherogenesis. Three distinct human monocyte subsets exist: classical CD14++CD16-, intermediate CD14++CD16+, and nonclassical CD14+CD16++ monocytes. Immunomodulation of distinct monocyte subsets has recently been discussed as a new therapeutic avenue in atherosclerosis.
Methods: Cardiovascular events in 951 subjects referred for elective coronary angiography were prospectively analyzed. Monocyte subset analysis was performed using flow cytometry, blinded to patients' clinical characteristics, and patients were categorized according to quartiles of total monocyte and monocyte subset counts. The primary endpoint was defined a priori as the first occurrence of cardiovascular death, acute myocardial infarction, or nonhemorrhagic stroke. Endpoint adjudication was done blinded to monocyte subset distribution.
Results: During a mean follow-up period of 2.6 ± 1.0 years, 93 patients experienced the primary endpoint. In univariate Kaplan-Meier analysis, counts of total (p = 0.010), classical CD14++CD16- (p = 0.024), and intermediate CD14++CD16+ (p < 0.001) monocytes predicted the primary endpoint, whereas nonclassical monocytes did not (p = 0.158). After full adjustment for confounders, CD14++CD16+ monocytes remained the only monocyte subset independently related to cardiovascular events (fourth vs. first quartile: hazard ratio: 3.019; 95% confidence interval: 1.315 to 6.928; p = 0.009).
Conclusions: CD14++CD16+ monocytes independently predicted cardiovascular events in subjects referred for elective coronary angiography. Future studies will be needed to elucidate whether CD14++CD16+ monocytes may become a target cell population for new therapeutic strategies in atherosclerosis.
Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Source: PubMed