The knowledge about diagnostic and prognostic value of cardiac and inflammatory biomarkers in patients with chronic coronary syndrome (CCS) is limited. To address this, we analyzed serum levels of selected biomarkers in 2536 patients with suspected CCS (35% female) from the Leipzig LIFE Heart Study who were admitted for coronary angiography. The median follow-up was 10 years. The following biomarkers were considered: high sensitive troponin T (hsTNT), N-terminal pro B-type natriuretic peptide (NT-proBNP), copeptin, high sensitive C-reactive protein (hsCRP) and interleukin‑6 (IL‑6). Patients were stratified according to the angiographic severity of coronary artery disease (CAD): CAD0 (no sclerosis), CAD1 (non-obstructive, i.e., stenosis < 50%), CAD2 (≥ one stenosis ≥ 50%). Group comparison (GC) included GC1: CAD0 + 1 vs. CAD2, GC2: CAD0 vs. CAD1 + 2. Using age-, sex and symptom-based pre-test probability (PTP) table for obstructive CAD (i.e. CAD 2) which was published in the current CCS guidelines, patients were further classified into the following three categories: PTP < 5% (n=559), PTP 5-15% (n=545) and PTP > 15% (n=1432).

CAD0, CAD1, CAD2 were apparent in 999, 529, and 1008 patients, respectively. Adjusted for traditional risk factors (TRF) and all considered biomarkers, hsTNT, NT-proBNP and IL-6 remained significant (hsTNT: p=2.0x10-10, NT-proBNP: p=0.049, IL6: p=0.030) in GC1. In GC2 only elevated hsTNT remained significant (p=1.9x10-7). In the ROC analysis only hsTNT slightly improved the AUC for the GC1-comparison in addition to TRF (0.729 with vs 0.712 witt hsTNT, p=0.013). Within the PTP subcategories the following results were obtained: PTP < 5%: AUC 0.747 with vs 0.730 without hsTNT, p<0.001; PTP 5-15 %: AUC 0.734 with vs 0.714 without hsTNT, p<0.001; PTP > 15%:  AUC 0.707 with vs 0.677 without hsTNT, p< 0.001). 10 years survival in groups CAD0, CAD1, CAD2 were 88.3%, 77.3%, 72.4%, respectively. In the multivariate analysis elevated hsTNT, NT-proBNP, copeptin and IL-6 remained significant mortality predictors in CAD2 patients with hazard ratios of similar magnitude (i.e. 1.5, 1.3, 1.4 and 1.3 per unit on the log-scale of the parameters, respectively). hsCRP did not reach significance. In the model stratified into tertiles according to the TRF and the biomarker levels except for hsCRP, the survival rates for tertiles were 93.9% (91.8%-96.1%), 81.4% (78.0%-85.0%) and 46.8% (42.5%-51.4%) Hazard rates were 3.13 (tertile 2 vs 1) and 11.2 (tertile 3 vs 1).

The studied cardiac and inflammatory biomarkers enable fast and precise non-invasive prediction of mortality risk in patients with suspected CCS, allowing tailored primary and secondary CAD prevention in this high-risk group. Furthermore hsTNT improved the detection of obstructive CAD particularly in patients with PTP > 15%.