title: Prognostic value of endothelial microparticles in patients with heart failure.
abstract: OBJECTIVE
  Heart failure (HF) is associated with endothelial dysfunction. Endothelium-derived microparticles (EMPs) are a novel quantitative plasma marker of endothelial dysfunction. We investigated whether plasma levels of EMPs can predict future cardiovascular events in patients with HF.
  
  
  RESULTS
  We enrolled 169 consecutive HF patients (70 ischaemic, 99 non-ischaemic HF) with New York Heart Association (NYHA) class I or more. Plasma CD144-positive EMP levels were measured by flow cytometry in the HF patients and in 31 healthy subjects. We followed the HF patients for mean 30 months. Endpoints were: a composite of cardiovascular events (myocardial infarction, stroke, re-hospitalization for HF, and cardiovascular death) and all-cause mortality. Endothelium-derived microparticle levels increased significantly with NYHA functional class [EMP median (range): healthy, 0.325 (0.164-0.354) ×10⁶/mL; NYHA I, 0.484 (0.426-0.575); II, 0.646 (0.439-0.795); and III/IV, 0.786 (0.569-1.026), P < 0.001]. A total of 33 cardiovascular events and 22 all-cause deaths were registered. Kaplan-Meier analysis demonstrated a significantly higher probability of cardiovascular events in the high-EMP group, but there was only a borderline difference for all-cause mortality (above median; log rank test P = 0.01, P = 0.053, respectively). Multivariate Cox regression analysis adjusted for clinical factors, identified high-EMP levels as an independent predictor of future cardiovascular events, but not for all-cause mortality in HF patients [hazard ratio (95% confidence interval): 2.423 (1.034-5.681), P = 0.04 for cardiovascular events; and 2.095 (0.825-5.323), P = 0.12 for all-cause mortality].
  
  
  CONCLUSIONS
  Endothelial dysfunction assessed by plasma levels of EMPs can independently predict future cardiovascular events in patients with HF. Endothelium-derived microparticles are a potentially useful biomarker of endothelial dysfunction in HF risk stratification.
authors.affiliation: Department of Cardiovascular Medicine, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto City, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Nozaki
authors.forename: Seigo
authors.initials: S
authors.lastname: Sugiyama
authors.forename: Koichi
authors.initials: K
authors.lastname: Sugamura
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ohba
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Matsuzawa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Konishi
authors.forename: Junichi
authors.initials: J
authors.lastname: Matsubara
authors.forename: Eiichi
authors.initials: E
authors.lastname: Akiyama
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sumida
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Matsui
authors.forename: Hideaki
authors.initials: H
authors.lastname: Jinnouchi
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D015820:Cadherins / Q000097:blood*; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000503:physiopathology*; D005260:Female; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000097:blood* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D015820:Cadherins; D020097:Natriuretic Peptide, Brain; D000099152:Cadherin 5