Aggregate risk score based on markers of inflammation, cell stress, and coagulation is an independent predictor of adverse cardiovascular outcomes.
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.
['Eapen|Danny J|DJ|', 'Manocha|Pankaj|P|', 'Patel|Riyaz S|RS|', 'Hammadah|Muhammad|M|', 'Veledar|Emir|E|', 'Wassel|Christina|C|', 'Nanjundappa|Ravi A|RA|', 'Sikora|Sergey|S|', 'Malayter|Dylan|D|', 'Wilson|Peter W F|PW|', 'Sperling|Laurence|L|', 'Quyyumi|Arshed A|AA|', 'Epstein|Stephen E|SE|']
D000368:Aged D015415:Biomarkers D002097:C-Reactive Protein D002318:Cardiovascular Diseases D015331:Cohort Studies D003324:Coronary Artery Disease D005260:Female D005338:Fibrin Fibrinogen Degradation Products D005500:Follow-Up Studies D018840:HSP70 Heat-Shock Proteins D006801:Humans D007249:Inflammation D008297:Male D008875:Middle Aged D011237:Predictive Value of Tests D012307:Risk Factors D012720:Severity of Illness Index
myocardial infarction MI biomarker C-reactive protein CRP fibrin degradation product fibrin degradation product FDP heat shock protein heat shock protein 70 HSP70 coronary artery disease CAD net reclassification improvement CABG CVD IDI LVEF NRI cardiovascular disease coronary artery bypass grafting eGFR estimated glomerular filtration rate fibrin degradation products integrated discrimination improvement left ventricular ejection fraction