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Original Investigation
August 5, 2020

Clinical Application of High-Sensitivity Troponin Testing in the Atherosclerotic Cardiovascular Disease Framework of the Current Cholesterol Guidelines

Author Affiliations
  • 1TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
  • 2Colorado Prevention Center (CPC) Clinical Research, Division of Cardiology, Department of Medicine, University of Colorado School of Medicine, Aurora
  • 3Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
  • 4Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
  • 5Division of Cardiology, Assistance Publique–Hôpitaux de Paris, Université de Paris, Paris, France
  • 6Newark Beth Israel Medical Center, Rutgers New Jersey Medical School, Newark
  • 7Division of Cardiology, The University of Sheffield, Sheffield, United Kingdom
  • 8AstraZeneca R&D, Gothenburg, Sweden
JAMA Cardiol. 2020;5(11):1255-1262. doi:10.1001/jamacardio.2020.2981
Key Points

Question  Can high-sensitivity troponin complement the American Heart Association/American College of Cardiology cholesterol management guidelines to improve atherosclerotic cardiovascular disease (ASCVD) risk classification?

Findings  Among 8635 patients in this cohort substudy, patients with lower-risk ASCVD and a high-sensitivity troponin I level exceeding 6 ng/L had the same rate of cardiovascular events as patients classified as having very high-risk ASCVD. Analogously, patients with very high-risk ASCVD and undetectable high-sensitivity troponin I level had event rates similar to those of patients classified as having lower-risk ASCVD.

Meaning  The findings of this cohort substudy suggest that incorporation of high-sensitivity troponin into a guideline-derived ASCVD risk algorithm provides enhanced risk stratification and reclassifies patients to ensure that risk-appropriate medical therapy is offered.

Abstract

Importance  The 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol management guidelines identified 2 distinct groups of patients with atherosclerotic cardiovascular disease (ASCVD) prompting different treatment recommendations.

Objective  To investigate whether the addition of high-sensitivity troponin (hsTn) testing to guideline-derived ASCVD risk can improve risk classification and downstream treatment recommendations.

Design, Setting, and Participants  A prospective cohort biomarker substudy was performed that included 8635 patients enrolled in the Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis in Myocardial Infarction 54 (PEGASUS-TIMI 54) trial. Patients were assigned to risk groups of either very high-risk ASCVD or lower-risk ASCVD based on their cardiovascular history and comorbidities, in line with the 2018 AHA/ACC cholesterol management guidelines criteria. Patients were also classified on the basis of hsTnI level (ARCHITECT assay; Abbott) using cut points of 2 ng/L (limit of detection) and 6 ng/L (risk threshold), followed by joint classification on the basis of clinical features and hsTnI level. The setting was a nested prospective cohort study in a completed multinational trial. Participants were all patients who had a myocardial infarction 1 to 3 years before enrollment, were at least 50 years of age, and had at least 1 high-risk feature. The study dates were October 2010 to December 2014. The dates of analysis were June 2019 to January 2020.

Main Outcomes and Measures  The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke.

Results  Among 8635 patients enrolled in the PEGASUS-TIMI 54 trial, the median age was 65 years (interquartile range, 58-71 years), and 6614 (76.6%) were men; 8340 (96.6%) were White individuals and 176 (2.0%) were Black individuals. Patients meeting clinical criteria for the very high-risk ASCVD group had a primary end point 3-year event rate of 8.8% compared with 5.0% in the lower-risk ASCVD group (hazard ratio, 2.01; 95% CI, 1.58-2.57; P < .001). When patients in the very high-risk ASCVD group were further risk stratified by hsTnI level, 614 of 6789 patients (9.0%) with an undetectable hsTnI level had a 3-year event rate of 2.7% (<1% per year), which was less than the overall rate in the lower-risk ASCVD group. Analogously, in the lower-risk ASCVD group, 417 of 1846 patients (22.6%) with an hsTnI level exceeding 6 ng/L had an event rate of 9.1%, comparable to the overall rate in the very high-risk ASCVD group. The addition of hsTnI to guideline-derived ASCVD risk led to a net reclassification index at event rate of 0.15 (95% CI, 0.10-0.21). Overall, use of hsTnI reclassified 1031 of 8635 patients (11.9%) (1 in 11 with very high-risk ASCVD and 1 in 4 with lower-risk ASCVD).

Conclusions and Relevance  The findings of this cohort substudy suggest that a strategy incorporating hsTn into a guideline-derived ASCVD risk algorithm provides enhanced risk stratification and reclassifies 11.9% of patients into a more appropriate risk group. This application of hsTn testing might be used to optimize the care of patients with ASCVD.

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