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

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  • Nima Ghasemzedah
  • Salim Hayek
  • Yi-An Ko
  • Danny J Eapen
  • Riyaz S Patel
  • Pankaj Manocha
  • Hatem Al Kassem
  • Mohamed Khayata
  • Emir Veledar
  • Dimitrios T Kremastinos
  • Christian W Thorball
  • Tomasz Pielak
  • Sergey Sikora
  • A Maziar Zafari
  • Stamatios Lerakis
  • Laurence Sperling
  • Viola Vaccarino
  • Stephen E Epstein
  • Arshed A Quyyumi
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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
JournalCirculation. Cardiovascular quality and outcomes
Volume10
Issue number3
ISSN1941-7713
DOIs
Publication statusPublished - Mar 2017

    Research areas

  • Journal Article

ID: 50144089