Soluble Urokinase-Type Plasminogen Activator Receptor and High-Sensitivity Troponin Levels Predict Outcomes in Nonobstructive Coronary Artery Disease

• Type of Material: Article
• Authors: Ahmed Al-Badri, Emory University; Ayman Samman Tahhan, Emory University; Nabil Sabbak, Emory University; Ayman Alkhoder, Emory University; Chang Liu, Emory University; Yi-An Ko, Emory University; Viola Vaccarino, Emory University; M. Afif Martini, Emory University; Arianna Sidoti, Emory University; Cydney Goodwin, Emory University; Bahjat Ghazzal, Emory University; Agim Beshiri, Abbott Labs; Gillian Murtagh, Abbott Labs; Puja Kiran Mehta, Emory University; Arshed Quyyumi, Emory University
• Language: English
• Date: 2020-04-21
• Publisher: Wiley
• Publication Version: Final Published Version
• Copyright Statement: © 2020 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1161/JAHA.119.015515
• Title of Journal or Parent Work: Journal of the American Heart Association
• Volume: 9
• Issue: 8
• Start Page: e015515
• End Page: e015515
• Grant/Funding Information: This work is also supported partially by Abbott Laboratories and Cardiorisk.; This work was supported by American Heart Association Postdoctoral Fellowship Award Grant (18POST34080330), the Abraham J. & Phyllis Katz Foundation grant (Atlanta, GA), National Institute on Aging grant (AG051633), National Institutes of Health grants (5P01HL101398‐02, 1P20HL113451‐01, 1R56HL126558‐01, 1RF1AG051633‐01, R01 NS064162‐01, R01 HL89650‐01, HL095479‐01, 1U10HL110302‐01, 1DP3DK094346‐01, and 2P01HL086773‐06A1).
• Keywords: ASSAY; angina; Cardiovascular System & Cardiology; no obstructive coronary artery disease; ischemia; adverse outcomes; HEART-DISEASE; Cardiac & Cardiovascular Systems; CHEST-PAIN; AMERICAN-COLLEGE; INOCA; suPAR; hsTnI; PREVALENCE; ASSOCIATION; Life Sciences & Biomedicine; MORTALITY; I LEVELS; Science & Technology; POPULATION; RISK
• Research Categories: Health Sciences, Epidemiology; Biology, Biostatistics; Health Sciences, Medicine and Surgery

Abstract

Background Multiple biomarkers have been independently and additively associated with major adverse cardiovascular events in patients with coronary artery disease. We investigated the prognostic value of suPAR (soluble urokinase-type plasminogen activator receptor) and hsTnI (high-sensitivity troponin I) levels in symptomatic patients with no obstructive coronary artery disease. We hypothesized that high levels of these biomarkers will be associated with the risk of future adverse outcomes. Methods and Results Plasma levels of suPAR and hsTnI were measured in 556 symptomatic patients with no obstructive coronary artery disease. A biomarker risk score was calculated by counting the number of biomarkers above the median in this cohort (suPAR>2523 pg/mL and hsTnI>2.7 pg/mL). Survival analyses were performed with models adjusted for traditional risk factors. All-cause death and major adverse cardiovascular events (cardiovascular death, myocardial infarction, stroke, and heart failure) served as clinical outcomes over a median follow-up of 6.2 years. Mean age was 57±10 years, 49% of the cohort patients were female, and 68% had a positive stress test. High suPAR and hsTnI levels were independent predictors of all-cause death (hazard ratio=3.2 [95% CI, 1.8-5.7] and 1.3 [95% CI, 1.0-1.7], respectively; both P<0.04) and major adverse cardiovascular events (hazard ratio=2.7 [95% CI, 1.4-5.4] and 1.5 [95% CI, 1.2-2.0], respectively; both P<0.002). Compared with a biomarker risk score of 0, biomarker risk scores of 1 and 2 were associated with 19- and 14-fold increased risk of death and development of major adverse cardiovascular events, respectively. Conclusions Among symptomatic patients with no obstructive coronary artery disease, higher levels of suPAR and hsTnI were independently and additively associated with an increased risk of adverse events. Whether modification of these biomarkers will improve risk in these patients needs further investigation.