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 Ghasemzedah; 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

doi:10.1161/CIRCOUTCOMES.115.001493

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

Circ Cardiovasc Qual Outcomes. 2017 Mar;10(3):e001493. doi: 10.1161/CIRCOUTCOMES.115.001493.

Authors

Nima Ghasemzedah¹, Salim S Hayek¹, Yi-An Ko¹, Danny J Eapen¹, Riyaz S Patel¹, Pankaj Manocha¹, Hatem Al Kassem¹, Mohamed Khayata¹, Emir Veledar¹, Dimitrios Kremastinos¹, Christian W Thorball¹, Tomasz Pielak¹, Sergey Sikora¹, A Maziar Zafari¹, Stamatios Lerakis¹, Laurence Sperling¹, Viola Vaccarino¹, Stephen E Epstein¹, Arshed A Quyyumi²

Affiliations

¹ From the Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA (N.G., S.S.H., D.J.E., R.S.P., P.M., H.A.K., M.K., E.V., A.M.Z., S.L., L.S., V.V., A.A.Q.); Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA (Y.-A.K.); Institute of Cardiovascular Science, University College London, United Kingdom (R.S.P.); Division of Cardiology, Atlanta VA Medical Center, GA (A.M.Z.); Department of Biostatistics, Florida International University, Miami (E.V.); Department of Cardiology, University of Athens School of Medicine, Greece (D.K.); Clinical Research Centre, Copenhagen University Hospital, Denmark (C.W.T., T.P.); Stemedica Cell Technologies, Inc., San Diego, CA (S.S.); Department of Epidemiology, Emory University, Atlanta, GA (V.V.); and MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC (S.E.E.).
² From the Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA (N.G., S.S.H., D.J.E., R.S.P., P.M., H.A.K., M.K., E.V., A.M.Z., S.L., L.S., V.V., A.A.Q.); Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA (Y.-A.K.); Institute of Cardiovascular Science, University College London, United Kingdom (R.S.P.); Division of Cardiology, Atlanta VA Medical Center, GA (A.M.Z.); Department of Biostatistics, Florida International University, Miami (E.V.); Department of Cardiology, University of Athens School of Medicine, Greece (D.K.); Clinical Research Centre, Copenhagen University Hospital, Denmark (C.W.T., T.P.); Stemedica Cell Technologies, Inc., San Diego, CA (S.S.); Department of Epidemiology, Emory University, Atlanta, GA (V.V.); and MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC (S.E.E.). aquyyum@emory.edu.

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.

Keywords: biomarker; cardiovascular outcomes; coronary artery disease; prognosis; risk score.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

Biomarkers
Fibrin Fibrinogen Degradation Products
HSP70 Heat-Shock Proteins
Receptors, Urokinase Plasminogen Activator
C-Reactive Protein

Abstract

Publication types

MeSH terms

Substances

Grants and funding