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Article in English | MEDLINE | ID: mdl-28280039

ABSTRACT

BACKGROUND: Inflammation, coagulation, and cell stress contribute to atherosclerosis and its adverse events. A biomarker risk score (BRS) based on the circulating levels of biomarkers C-reactive protein, fibrin degradation products, and heat shock protein-70 representing these 3 pathways was a strong predictor of future outcomes. We investigated whether soluble urokinase plasminogen activator receptor (suPAR), a marker of immune activation, is predictive of outcomes independent of the aforementioned markers and whether its addition to a 3-BRS improves risk reclassification. METHODS AND RESULTS: C-reactive protein, fibrin degradation product, heat shock protein-70, and suPAR were measured in 3278 patients undergoing coronary angiography. The BRS was calculated by counting the number of biomarkers above a cutoff determined using the Youden's index. Survival analyses were performed using models adjusted for traditional risk factors. A high suPAR level ≥3.5 ng/mL was associated with all-cause death and myocardial infarction (hazard ratio, 1.83; 95% confidence interval, 1.43-2.35) after adjustment for risk factors, C-reactive protein, fibrin degradation product, and heat shock protein-70. Addition of suPAR to the 3-BRS significantly improved the C statistic, integrated discrimination improvement, and net reclassification index for the primary outcome. A BRS of 1, 2, 3, or 4 was associated with a 1.81-, 2.59-, 6.17-, and 8.80-fold increase, respectively, in the risk of death and myocardial infarction. The 4-BRS was also associated with severity of coronary artery disease and composite end points. CONCLUSIONS: SuPAR is independently predictive of adverse outcomes, and its addition to a 3-BRS comprising C-reactive protein, fibrin degradation product, and heat shock protein-70 improved risk reclassification. The clinical utility of using a 4-BRS for risk prediction and management of patients with coronary artery disease warrants further study.


Subject(s)
C-Reactive Protein/analysis , Coronary Artery Disease/diagnostic imaging , Fibrin Fibrinogen Degradation Products/analysis , HSP70 Heat-Shock Proteins/blood , Myocardial Infarction/etiology , Receptors, Urokinase Plasminogen Activator/blood , Aged , Biomarkers/blood , Coronary Angiography , Coronary Artery Disease/blood , Coronary Artery Disease/complications , Coronary Artery Disease/mortality , Disease Progression , Female , Humans , Male , Middle Aged , Myocardial Infarction/diagnosis , Myocardial Infarction/mortality , Predictive Value of Tests , Prognosis , Proportional Hazards Models , Risk Assessment , Risk Factors , Severity of Illness Index
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