Ghasemzadeh, N;
Hayek, SS;
Ko, Y-A;
Eapen, DJ;
Patel, RS;
Manocha, P;
Al Kassem, H;
... Quyyumi, AA; + view all
(2017)
Pathway-Specific Aggregate Biomarker Risk Score Is Associated With Burden of Coronary Artery Disease and Predicts Near-Term Risk of Myocardial Infarction and Death.
Circulation: Cardiovascular Quality and Outcomes
, 10
(3)
, Article e001493. 10.1161/CIRCOUTCOMES.115.001493.
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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.
| Type: | Article |
|---|---|
| Title: | Pathway-Specific Aggregate Biomarker Risk Score Is Associated With Burden of Coronary Artery Disease and Predicts Near-Term Risk of Myocardial Infarction and Death |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1161/CIRCOUTCOMES.115.001493 |
| Publisher version: | http://doi.org/10.1161/CIRCOUTCOMES.115.001493 |
| Language: | English |
| Additional information: | © 2017 American Heart Association, Inc. This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Cardiac & Cardiovascular Systems, Cardiovascular System & Cardiology, biomarker, cardiovascular outcomes, coronary artery disease, prognosis, risk score, PLASMINOGEN-ACTIVATOR RECEPTOR, C-REACTIVE PROTEIN, CARDIOVASCULAR-DISEASE, HEART-DISEASE, UROKINASE RECEPTOR, GENERAL-POPULATION, CELL-ADHESION, MORTALITY, CANCER, ATHEROSCLEROSIS |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1548954 |
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