title: CD14++CD16+ monocytes independently predict cardiovascular events: a cohort study of 951 patients referred for elective coronary angiography.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Internal Medicine IV, Saarland University Medical Center, Homburg/Saar, Germany.
authors.forename: Kyrill S
authors.initials: KS
authors.lastname: Rogacev
authors.forename: Bodo
authors.initials: B
authors.lastname: Cremers
authors.forename: Adam M
authors.initials: AM
authors.lastname: Zawada
authors.forename: Sarah
authors.initials: S
authors.lastname: Seiler
authors.forename: Nadine
authors.initials: N
authors.lastname: Binder
authors.forename: Philipp
authors.initials: P
authors.lastname: Ege
authors.forename: Gunnar
authors.initials: G
authors.lastname: Große-Dunker
authors.forename: Isabel
authors.initials: I
authors.lastname: Heisel
authors.forename: Florian
authors.initials: F
authors.lastname: Hornof
authors.forename: Jana
authors.initials: J
authors.lastname: Jeken
authors.forename: Niko M
authors.initials: NM
authors.lastname: Rebling
authors.forename: Christof
authors.initials: C
authors.lastname: Ulrich
authors.forename: Bruno
authors.initials: B
authors.lastname: Scheller
authors.forename: Michael
authors.initials: M
authors.lastname: Böhm
authors.forename: Danilo
authors.initials: D
authors.lastname: Fliser
authors.forename: Gunnar H
authors.initials: GH
authors.lastname: Heine
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000276:immunology*; D015331:Cohort Studies; D017023:Coronary Angiography; D005260:Female; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D007958:Leukocyte Count; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D011237:Predictive Value of Tests; D017452:Receptors, IgG / Q000378:metabolism*; D012044:Regression Analysis; D012307:Risk Factors
chemical_list: C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG