A substantial residual risk exists for long-term cardiovascular (CV) mortality in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). Atherosclerotic plaque rupture has been linked to the lysosomal cysteine protease cathepsin S (CTSS), which possesses elastolytic and collagenolytic activity. For a study, researchers set out to ascertain the following things: The predictive utility of circulating CTSS assessed at patient admission for long-term mortality in NSTE-ACS; and Its value as an additive factor above the GRACE (Global Registry of Acute Coronary Events) risk score.

The emergency department of an academic hospital provided the participants for this single-center cohort research (n = 1,112) of patients with adjudicated NSTE-ACS. Using an enzyme-linked immunosorbent test, CTSS was calculated in serum. The main outcome was all-cause death at 8 years. The secondary outcome was death from CV.

Deaths were reported in 367 (33.2%) total cases. After accounting for conventional CV risk factors, high-sensitivity C-reactive protein, left ventricular ejection fraction, high-sensitivity troponin-T, revascularization, and the index diagnosis (unstable angina/non-ST-segment elevation myocardial infarction), CTSS was linked to an 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). Furthermore, even after taking into account high-sensitivity troponin-T and left ventricular ejection fraction, CTSS added to GRACE score provided 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 & left ventricular ejection fraction. 

Circulating CTSS outperformed the GRACE score in risk categorization for patients with NSTE-ACS and is a predictor of long-term death.

Reference: jacc.org/doi/10.1016/j.jacc.2022.05.055