Pathway-Specific Aggregate Biomarker Risk Score Is Associated with Burden of Coronary Artery Disease and Predicts Near-Term Risk of Myocardial Infarction and Death

Nima Ghasemzadeh, Salim S. Hayek, Yi An Ko, Danny J. Eapen, Riyaz S. Patel, Pankaj Manocha, Hatem Al Kassem, Mohamed Khayata, Emir Veledar, Dimitrios Kremastinos, Christian W. Thorball, Tomasz Pielak, Sergey Sikora, A. Maziar Zafari, Stamatios Lerakis, Laurence Sperling, Viola Vaccarino, Stephen E. Epstein, Arshed A. Quyyumi

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

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.

Original languageEnglish
Article numbere001493
JournalCirculation: Cardiovascular Quality and Outcomes
Volume10
Issue number3
DOIs
StatePublished - 1 Mar 2017
Externally publishedYes

Keywords

  • biomarker
  • cardiovascular outcomes
  • coronary artery disease
  • prognosis
  • risk score

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