Article ; Online: Cathepsin S Levels and Survival Among Patients With Non-ST-Segment Elevation Acute Coronary Syndromes.
Journal of the American College of Cardiology
2022 Volume 80, Issue 10, Page(s) 998–1010
Abstract: ... residual risk for long-term cardiovascular (CV) mortality. Cathepsin S (CTSS) is a lysosomal cysteine protease ...
| Abstract | Background: Patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) are at high residual risk for long-term cardiovascular (CV) mortality. Cathepsin S (CTSS) is a lysosomal cysteine protease with elastolytic and collagenolytic activity that has been involved in atherosclerotic plaque rupture. Objectives: The purpose of this study was to determine the following: 1) the prognostic value of circulating CTSS measured at patient admission for long-term mortality in NSTE-ACS; and 2) its additive value over the GRACE (Global Registry of Acute Coronary Events) risk score. Methods: This was a single-center cohort study, consecutively recruiting patients with adjudicated NSTE-ACS (n = 1,112) from the emergency department of an academic hospital. CTSS was measured in serum using enzyme-linked immunosorbent assay. All-cause mortality at 8 years was the primary endpoint. CV death was the secondary endpoint. Results: In total, 367 (33.0%) deaths were recorded. CTSS was associated with increased risk of all-cause mortality (HR for highest vs lowest quarter of CTSS: 1.89; 95% CI: 1.34-2.66; P < 0.001) and CV death (HR: 2.58; 95% CI: 1.15-5.77; P = 0.021) after adjusting for traditional CV risk factors, high-sensitivity C-reactive protein, left ventricular ejection fraction, high-sensitivity troponin-T, revascularization and index diagnosis (unstable angina/ non-ST-segment elevation myocardial infarction). When CTSS was added to the GRACE score, it conferred significant discrimination and reclassification value for all-cause mortality (Delta Harrell's C: 0.03; 95% CI: 0.012-0.047; P = 0.001; and net reclassification improvement = 0.202; P = 0.003) and CV death (AUC: 0.056; 95% CI: 0.017-0.095; P = 0.005; and net reclassification improvement = 0.390; P = 0.001) even after additionally considering high-sensitivity troponin-T and left ventricular ejection fraction. Conclusions: Circulating CTSS is a predictor of long-term mortality and improves risk stratification of patients with NSTE-ACS over the GRACE score. |
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| MeSH term(s) | Acute Coronary Syndrome/diagnosis ; Cathepsins/blood ; Cohort Studies ; Humans ; Non-ST Elevated Myocardial Infarction/diagnosis ; Prognosis ; Risk Assessment ; Stroke Volume ; Troponin T ; Ventricular Function, Left |
| Chemical Substances | Troponin T ; Cathepsins (EC 3.4.-) ; cathepsin S (EC 3.4.22.27) |
| Language | English |
| Publishing date | 2022-09-01 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 605507-2 |
| ISSN | 1558-3597 ; 0735-1097 |
| ISSN (online) | 1558-3597 |
| ISSN | 0735-1097 |
| DOI | 10.1016/j.jacc.2022.05.055 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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