title: Aggregate risk score based on markers of inflammation, cell stress, and coagulation is an independent predictor of adverse cardiovascular outcomes.
abstract: OBJECTIVE
  This study sought to determine an aggregate, pathway-specific risk score for enhanced prediction of death and myocardial infarction (MI).
  
  
  BACKGROUND
  Activation of inflammatory, coagulation, and cellular stress pathways contribute to atherosclerotic plaque rupture. We hypothesized that an aggregate risk score comprised of biomarkers involved in these different pathways-high-sensitivity C-reactive protein (CRP), fibrin degradation products (FDP), and heat shock protein 70 (HSP70) levels-would be a powerful predictor of death and MI.
  
  
  METHODS
  Serum levels of CRP, FDP, and HSP70 were measured in 3,415 consecutive patients with suspected or confirmed coronary artery disease (CAD) undergoing cardiac catheterization. Survival analyses were performed with models adjusted for established risk factors.
  
  
  RESULTS
  Median follow-up was 2.3 years. Hazard ratios (HRs) for all-cause death and MI based on cutpoints were as follows: CRP ≥3.0 mg/l, HR: 1.61; HSP70 >0.625 ng/ml, HR; 2.26; and FDP ≥1.0 μg/ml, HR: 1.62 (p < 0.0001 for all). An aggregate biomarker score between 0 and 3 was calculated based on these cutpoints. Compared with the group with a 0 score, HRs for all-cause death and MI were 1.83, 3.46, and 4.99 for those with scores of 1, 2, and 3, respectively (p for each: <0.001). Annual event rates were 16.3% for the 4.2% of patients with a score of 3 compared with 2.4% in 36.4% of patients with a score of 0. The C statistic and net reclassification improved (p < 0.0001) with the addition of the biomarker score.
  
  
  CONCLUSIONS
  An aggregate score based on serum levels of CRP, FDP, and HSP70 is a predictor of future risk of death and MI in patients with suspected or known CAD.
authors.affiliation: Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Danny J
authors.initials: DJ
authors.lastname: Eapen
authors.forename: Pankaj
authors.initials: P
authors.lastname: Manocha
authors.forename: Riyaz S
authors.initials: RS
authors.lastname: Patel
authors.forename: Muhammad
authors.initials: M
authors.lastname: Hammadah
authors.forename: Emir
authors.initials: E
authors.lastname: Veledar
authors.forename: Christina
authors.initials: C
authors.lastname: Wassel
authors.forename: Ravi A
authors.initials: RA
authors.lastname: Nanjundappa
authors.forename: Sergey
authors.initials: S
authors.lastname: Sikora
authors.forename: Dylan
authors.initials: D
authors.lastname: Malayter
authors.forename: Peter W F
authors.initials: PW
authors.lastname: Wilson
authors.forename: Laurence
authors.initials: L
authors.lastname: Sperling
authors.forename: Arshed A
authors.initials: AA
authors.lastname: Quyyumi
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Epstein
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D005500:Follow-Up Studies; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D018840:HSP70 Heat-Shock Proteins; D002097:C-Reactive Protein
keywords: C-reactive protein; CABG; CAD; CRP; CVD; FDP; HSP70; IDI; LVEF; MI; NRI; biomarker; cardiovascular disease; coronary artery bypass grafting; coronary artery disease; eGFR; estimated glomerular filtration rate; fibrin degradation product; fibrin degradation products; heat shock protein; heat shock protein 70; integrated discrimination improvement; left ventricular ejection fraction; myocardial infarction; net reclassification improvement