title: An elevated ratio of placental growth factor to soluble fms-like tyrosine kinase-1 predicts adverse outcomes in patients with stable coronary artery disease.
abstract: OBJECTIVE
  To investigate the predictive values of placental growth factor (PlGF) and its endogenous antagonist, soluble fms-like tyrosine kinase-1 (sFlt-1), for the long-term prognosis of patients with stable coronary artery disease (CAD). Both PlGF and sFlt-1 play important roles in the pathological mechanisms of atherosclerosis. We recently demonstrated that the plasma levels of these molecules are correlated with the severity of coronary atherosclerosis.
  
  
  METHODS
  We enrolled 464 patients with stable CAD who consecutively underwent coronary angiography. Baseline blood samples were collected from the femoral artery immediately before coronary angiography (after the administration of 20 units of heparin), and the plasma levels of PlGF and sFlt-1 were measured. A Cox proportional hazard regression analysis was performed to evaluate the relationship between these parameters and the occurrence of all-cause death (ACD) and total cardiovascular events (TCVE) during a median follow-up of 3.3 years.
  
  
  RESULTS
  A total of 31 ACDs and 51 TCVEs occurred. Patients with higher PlGF/sFlt-1 ratios (>4.22×10(-2)) had a significantly higher risk of both ACD and TCVE than patients with lower ratios (<4.22×10(-2)) (hazard ratio [HR]: 3.32, 95% confidence interval [CI]: 1.43 to 7.72, p=0.005, and HR: 2.23, 95% CI: 1.23 to 4.03, p=0.008, respectively). A multivariate analysis showed the PlGF/sFlt-1 ratio to be an independent predictor for ACD, but not TCVE.
  
  
  CONCLUSIONS
  The baseline PlGF/sFlt-1 ratio is an independent predictor of long-term adverse outcomes in patients with stable CAD.
authors.affiliation: The First Department of Internal Medicine, Nara Medical University, Japan.
authors.forename: Takaki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Shiro
authors.initials: S
authors.lastname: Uemura
authors.forename: Yukiji
authors.initials: Y
authors.lastname: Takeda
authors.forename: Masaru
authors.initials: M
authors.lastname: Matsui
authors.forename: Sadanori
authors.initials: S
authors.lastname: Okada
authors.forename: Taku
authors.initials: T
authors.lastname: Nishida
authors.forename: Tsunenari
authors.initials: T
authors.lastname: Soeda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okayama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Somekawa
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Ishigami
authors.forename: Kenji
authors.initials: K
authors.lastname: Onoue
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kawata
authors.forename: Rika
authors.initials: R
authors.lastname: Kawakami
authors.forename: Manabu
authors.initials: M
authors.lastname: Horii
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Saito
mesh_terms: D000368:Aged; D015415:Biomarkers; D002317:Cardiovascular Agents / Q000627:therapeutic use; D002423:Cause of Death; D015897:Comorbidity; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood* / Q000150:complications / Q000000981:diagnostic imaging / Q000401:mortality / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000453:epidemiology / Q000209:etiology; D006801:Humans; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000209:etiology; D062645:Percutaneous Coronary Intervention; D000072483:Placenta Growth Factor; D010949:Plasma; D011257:Pregnancy Proteins / Q000097:blood*; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology; D016896:Treatment Outcome; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
chemical_list: D015415:Biomarkers; D002317:Cardiovascular Agents; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1