Cathepsin S Levels and Survival Among Patients With Non-ST-Segment Elevation Acute Coronary Syndromes
Kimon Stamatelopoulos1, Matthias Mueller-Hennessen2, Georgios Georgiopoulos1
1Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece; Biosciences Institute, Vascular Biology and Medicine Theme, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom.
Insights
Cathepsin S (CTSS) predicts long-term mortality in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). Measuring CTSS improves risk stratification beyond the GRACE score for these high-risk cardiovascular patients.
Area of Science:
- Cardiology
- Biochemistry
- Proteomics
Background:
- Patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) face significant long-term cardiovascular mortality risk.
- Cathepsin S (CTSS), a protease involved in atherosclerotic plaque rupture, is a potential biomarker for cardiovascular events.
Purpose of the Study:
- To evaluate the prognostic value of serum CTSS levels upon admission for long-term mortality in NSTE-ACS patients.
- To assess the additive value of CTSS to the established GRACE risk score for risk stratification.
Main Methods:
- A single-center cohort study included 1,112 patients with NSTE-ACS.
- Serum CTSS was quantified using enzyme-linked immunosorbent assay.
- All-cause and cardiovascular (CV) death at 8 years were the primary and secondary endpoints, respectively.
Main Results:
- Elevated CTSS levels were significantly associated with increased risk of all-cause mortality (HR: 1.89) and CV death (HR: 2.58) after multivariable adjustment.
- Adding CTSS to the GRACE score significantly improved discrimination and reclassification for both all-cause mortality (Delta Harrell's C: 0.03) and CV death (AUC: 0.056).
Conclusions:
- Circulating CTSS is a valuable predictor of long-term mortality in NSTE-ACS patients.
- CTSS measurement enhances the risk stratification capabilities of the GRACE score for NSTE-ACS patients.
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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