title: Elevated concentration of placental growth factor (PlGF) and long term risk in patients with acute coronary syndrome in the PROVE IT-TIMI 22 trial.
abstract: Placental growth factor (PlGF), a member of the vascular endothelial growth factor (VEGF) family, acts via the flt-1 receptor and promotes endothelial activation and macrophage recruitment into atherosclerotic lesions. We investigated the relationship of PlGF with cardiovascular outcomes in a large cohort of patients presenting across the spectrum of ACS. PlGF was measured at baseline (n = 3,761) and at four-months (n = 3,369) in patients randomized to atorvastatin 80 mg or pravastatin 40 mg after ACS in the PROVE IT-TIMI 22 trial. The primary endpoint was death, myocardial infarction (MI), unstable angina, revascularization or stroke (mean follow-up 24 months). Elevated baseline PlGF was associated with a higher incidence of the primary endpoint through 2 years (Q1 vs. Q5: 18.7 vs. 29.3%, p < 0.0001). The risk of death or MI was also higher in patients with elevated baseline PlGF (Q1 vs. Q5: 7.0 vs. 11.6%, p = 0.029). Adjusting for baseline characteristics and risk factors, elevated baseline PlGF was independently associated with the risk of the primary endpoint (adjusted-HR for Q5 vs. Q1 1.45; 95% CI 1.16-1.83; p = 0.001). Elevated PlGF at four months was associated with higher risk of death or MI (Adjusted HR Q5 vs. Q1 2.79, 95% CI: 1.37-5.68; p = 0.005), and higher risk of the primary endpoint (Adjusted HR Q5 vs. Q1 1.78, 95% CI: 1.26-2.51; p = 0.001). Higher concentration of PlGF after ACS is associated with long-term risk of recurrent cardiovascular events independent of traditional risk factors. This association is present early after ACS and appears to be stronger at four months.
authors.affiliation: Thrombolysis in Myocardial Infarction (TIMI) Study Group, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 350 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: An H
authors.initials: AH
authors.lastname: Bui
authors.forename: Marc P
authors.initials: MP
authors.lastname: Bonaca
authors.forename: Marc S
authors.initials: MS
authors.lastname: Sabatine
authors.forename: Kausik K
authors.initials: KK
authors.lastname: Ray
authors.forename: Nader
authors.initials: N
authors.lastname: Rifai
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon
authors.forename: David A
authors.initials: DA
authors.lastname: Morrow
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000401:mortality; D000368:Aged; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000209:etiology / Q000401:mortality; D000072483:Placenta Growth Factor; D017035:Pravastatin / Q000008:administration & dosage*; D011257:Pregnancy Proteins / Q000097:blood*; D011758:Pyrroles / Q000008:administration & dosage*; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D011758:Pyrroles; D000072483:Placenta Growth Factor; D000069059:Atorvastatin; D017035:Pravastatin