Author + information
- Received September 10, 2018
- Revision received October 10, 2018
- Accepted October 15, 2018
- Published online January 21, 2019.
- James L. Januzzi Jr., MDa,b,∗ (, )@JJheart_doc,
- Sunil Suchindran, PhDc,
- Udo Hoffmann, MDd,
- Manesh R. Patel, MDe,f,
- Maros Ferencik, MD, PhDg,
- Adrian Coles, PhDe,
- Jean-Claude Tardif, MDh,
- Geoffrey S. Ginsburg, MDc,f,
- Pamela S. Douglas, MDe,f,
- on behalf of the PROMISE Investigators
- aCardiology Division, Massachusetts General Hospital, Boston, Massachusetts
- bBaim Institute for Clinical Research, Boston, Massachusetts
- cDuke Center for Applied Genomics and Precision Medicine, Durham, North Carolina
- dDepartment of Radiology, Massachusetts General Hospital, Boston, Massachusetts
- eDuke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
- fDepartment of Medicine, Duke University School of Medicine, Durham, North Carolina
- gOregon Health and Science University, Portland, Oregon
- hMontreal Heart Institute, Université de Montréal, Montreal, Canada
- ↵∗Address for correspondence:
Dr. James L. Januzzi, Jr., Cardiology Division, Massachusetts General Hospital. Yawkey 5984, 32 Fruit Street, Boston, Massachusetts 02114.
Background Evaluation of stable symptomatic outpatients with suspected coronary artery disease (CAD) may be challenging because they have a wide range of cardiovascular risk. The role of troponin testing to assist clinical decision making in this setting is unexplored.
Objectives This study sought to evaluate the prognostic meaning of single-molecule counting high-sensitivity troponin I (hsTnI) (normal range <6 ng/l) among outpatients with stable chest symptoms and suspected CAD.
Methods Participants with available blood samples in PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) were studied, and hsTnI results were analyzed relative to the primary outcome of death, acute myocardial infarction (MI), or hospitalization for unstable angina by 1 year. The secondary outcome was the composite of cardiovascular death or acute MI.
Results The study sample consisted of 4,021 participants; 98.6% had measurable hsTnI concentrations. The median hsTnI value was 1.6 ng/l. In upper hsTnI quartiles, patients had higher-risk clinical profiles. Higher hsTnI concentrations were associated with greater event probabilities for death, acute MI, or hospitalization for unstable angina. In multivariable models, hsTnI concentrations independently predicted death, acute MI, or hospitalization for unstable angina (hazard ratio: 1.54 per increase in log-hsTnI interquartile range; p < 0.001) and cardiovascular death or acute MI (hazard ratio: 1.52 per increase in log-hsTnI interquartile range; p < 0.001) and were particularly associated with near-term events, compared with longer follow-up.
Conclusions In symptomatic outpatients with suspected CAD, higher concentrations of hsTnI within the normal range were associated with heightened near-term risk for death, acute MI, or hospitalization. (Prospective Multicenter Imaging Study for Evaluation of Chest Pain [PROMISE]; NCT01174550)
This work was sponsored in part by an unrestricted grant from Singulex, Inc. This project was also supported by grants R01HL098237, R01HL098236, and R01HL98305 from the National Heart, Lung, and Blood Institute (NHLBI). Dr. Januzzi is supported in part by the Hutter Family Professorship in Cardiology; has received grant support from Singulex, Abbott, and Prevencio; has received consulting income from Roche Diagnostics, Critical Diagnostics, Philips, Abbott, Prevencio, and Novartis; and participates in clinical endpoint committees or data safety monitoring boards for Siemens, Abbvie, Pfizer, Amgen, Janssen, and Boehringer Ingelheim. Dr. Hoffmann has received institutional research grants from Abbott, HeartFlow, Kowa Pharmaceuticals, and Medimmune. Dr. Patel has received research grants from AstraZeneca, Janssen, Bayer, NHLBI, Philips, and Heartflow; and serves on advisory boards for Janssen, AstraZeneca, and Bayer. Dr. Ferencik was supported in part by American Heart Association Fellow to Faculty Award 13FTF16450001. Dr. Tardif holds the Canada Research Chair in personalized and translational medicine; has received research funding from Amarin, AstraZeneca, DalCor, Esperion, Ionis, Merck, Pfizer, Sanofi, and Servier; has received honoraria from DalCor, Pfizer, Sanofi, and Servier; and holds a minor equity interest in DalCor. Dr. Ginsburg has served as a consultant or advisory board member for CardioDx, Interleukin Genetics, Pappas Ventures, Fabric Genomics, Genome Magazine, Exploragen, Origin Commercial Advisors, and Dr. Footprint; has stock options from CardioDx, Alere, Fabric Genomics, Predigen, Exploragen, Dr. Footprint, and Origin Commercial Advisors; has served on the board of directors for Alere; has received royalties from Elsevier; has received research funding to his institution from Singulex, Abbott, and 23andMe; and is a founder of Predigen. Dr. Douglas has received research grants from GE Healthcare and HeartFlow. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Allan S. Jaffee, MD, served as Guest Editor for this paper.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Received September 10, 2018.
- Revision received October 10, 2018.
- Accepted October 15, 2018.
- 2019 American College of Cardiology Foundation
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