Aggregate risk score based on markers of inflammation, cell stress, and coagulation is an independent predictor of adverse cardiovascular outcomes

J Am Coll Cardiol. 2013 Jul 23;62(4):329-37. doi: 10.1016/j.jacc.2013.03.072. Epub 2013 May 9.


Objectives: 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.

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.

MeSH terms

  • Aged
  • Biomarkers / blood
  • C-Reactive Protein / metabolism*
  • Cardiovascular Diseases / metabolism*
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / pathology*
  • Cohort Studies
  • Coronary Artery Disease / metabolism*
  • Coronary Artery Disease / mortality
  • Coronary Artery Disease / pathology*
  • Female
  • Fibrin Fibrinogen Degradation Products / metabolism*
  • Follow-Up Studies
  • HSP70 Heat-Shock Proteins / metabolism*
  • Humans
  • Inflammation / metabolism
  • Inflammation / mortality
  • Inflammation / pathology
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Risk Factors
  • Severity of Illness Index*


  • Biomarkers
  • Fibrin Fibrinogen Degradation Products
  • HSP70 Heat-Shock Proteins
  • C-Reactive Protein