https://doi.org/10.1007/s00392-025-02625-4
1Universitätsklinikum OWL Klinik für Kardiologie und intern. Intensivmedizin Bielefeld, Deutschland; 2Dekanat der Medizinischen Fakultät Kiel, Deutschland; 3Herzzentrum Leipzig - Universität Leipzig Klinik für Innere Medizin/Kardiologie Leipzig, Deutschland; 4University of Leipzig IMISE Leipzig, Deutschland
INTRODUCTION AND METHODS: The net diagnostic benefit of non-invasive assessment for pre-test probability of relevant coronary obstruction remains consistently low, as reflected in current guidelines for chronic coronary syndrome (CCS) management. Furthermore, the incremental predictive value of cardiovascular biomarkers in the CCS setting has not been fully elucidated.
To address this gap, we analyzed serum levels of selected biomarkers in 2,251 high risk patients with suspected CCS (35.5% female) from the Leipzig LIFE Heart Study who underwent coronary angiography. The median follow-up was 11.2 years. We evaluated high-sensitive troponin T (hsTNT), N-terminal pro B-type natriuretic peptide (NT-proBNP), and copeptin. Patients were stratified according to angiographic coronary artery disease (CAD) severity: CAD0 (i.e. no CAD or non-obstructive coronary sclerosis) and CAD1 (i.e. ≥ one stenosis ≥ 50% in any major epicardial coronary artery). Using the age-, sex-, symptom-, and risk-factor score (RFS)-based pre-test probability (PTP) prediction matrix for obstructive CAD published in current 2024 CCS guidelines, patients were classified into three categories: PTP < 5% (n=307), PTP 5-15% (n=950), and PTP > 15% (n=994).
RESULTS: CAD0 and CAD1 were identified in 1,363 and 888 patients, respectively. Of CAD1 patients, 611 (68.8%) underwent revascularization. Across PTP subgroups, CAD1 prevalence was: PTP <5%: 47 (15.3%); PTP 5-15%: 313 (32.9%); PTP >15%: 528 (53.1%) (p for interaction < 0.001). After adjustment for traditional risk factors (TRF), hsTNT and NT-proBNP levels showed significant differences (hsTNT: p=2.0x10-10, NT-proBNP: p=0.049). In ROC analysis, only hsTNT modestly improved the AUC in addition to TRF (0.669 vs 0.702 with hsTNT, p=0.013). Within PTP subcategories, hsTNT implementation yielded the following improvements in CAD1 detection: PTP < 5%: AUChsTropT 0.692; PTP 5-15%: AUChsTropT 0.620; PTP > 15%: AUChsTropT 0.596 (p< 0.001). In the intermediate PTP 5-15% subgroup, an hsTropT cut-off value < 3 pg/mL (N= 119/23.4%) demonstrated 89.7% sensitivity and 73.1% specificity for CAD1 detection. Adding glomerular filtration rate, body mass index, waist-hip ratio, HDL cholesterol, and triglyceride levels as potential risk factors did not substantially alter the model across subgroups.
During the median follow-up, survival rates were 97.8% in PTP <5%, 94.4% in PTP 5-15%, and 87.2% in PTP>15% subgroups, respectively (p=0.002). hsTropT values above the median 7.7 ng/dl were independently associated with borderline lower survival in PTP < 5% subgroup (chi-square 15.05; p=0.055), and improved survival in intermediate PTP 5-15% subrougp (chi-square 6.98; p=0.015), whereas no relationship was found in PTP > 15% even after adjustment for angiographic coronary status and revascularisation.
CONCLUSIONS: Our study demonstrates that hsTNT provides incremental value in detecting obstructive CAD beyond the current PTP-model recommended by CCS guidelines, particularly in patients allocated to the PTP 5-15% subgroup. Furthermore, hsTropT improved non-invasive prediction of mortality risk in patients with suspected CCS, enabling tailored primary and secondary CAD prevention in this high-risk population.