An elevated ratio of placental growth factor to soluble fms-like tyrosine kinase-1 predicts adverse outcomes in patients with stable coronary artery disease

Intern Med. 2013;52(10):1019-27. doi: 10.2169/internalmedicine.52.9073. Epub 2013 May 15.

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.

Conclusion: The baseline PlGF/sFlt-1 ratio is an independent predictor of long-term adverse outcomes in patients with stable CAD.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Biomarkers
  • Cardiovascular Agents / therapeutic use
  • Cause of Death
  • Comorbidity
  • Coronary Angiography
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / complications
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / mortality
  • Coronary Artery Disease / therapy
  • Female
  • Follow-Up Studies
  • Heart Failure / epidemiology
  • Heart Failure / etiology
  • Humans
  • Kaplan-Meier Estimate
  • Kidney Failure, Chronic / epidemiology
  • Male
  • Middle Aged
  • Myocardial Infarction / epidemiology
  • Myocardial Infarction / etiology
  • Percutaneous Coronary Intervention
  • Placenta Growth Factor
  • Plasma
  • Pregnancy Proteins / blood*
  • Prognosis
  • Proportional Hazards Models
  • Risk Factors
  • Stroke / epidemiology
  • Treatment Outcome
  • Vascular Endothelial Growth Factor Receptor-1 / blood*

Substances

  • Biomarkers
  • Cardiovascular Agents
  • PGF protein, human
  • Pregnancy Proteins
  • Placenta Growth Factor
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1