Cardiac Biomarkers to Refine Pretest Probability for Coronary Obstruction and Predict Survival After Revascularization in Chronic Coronary Syndrome

Background The diagnostic and prognostic roles of cardiovascular biomarkers in chronic coronary syndrome remain unclear. Methods Patients undergoing coronary angiography for suspected chronic coronary syndrome were prospectively enrolled (n=2251; median follow‐up 12.6 years). Obstructive coronary artery disease was defined as ≥50% stenosis in ≥1 major epicardial vessel. HsTnT (high‐sensitivity cardiac troponin T), NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), high‐sensitivity C‐reactive protein, interleukin‐6, and copeptin were measured. Receiver operating characteristic analysis and Cox regression with biomarker × treatment interaction testing were performed. Results Overall, 888 patients (39.4%) had obstructive coronary artery disease. Only hsTnT showed meaningful diagnostic capacity (area under the curve 0.669; risk factor‐weighted clinical likelihood area under the curve 0.663), with incremental benefit inversely proportional to risk factor‐weighted clinical likelihood category (Δ area under the curve: very low 10.4%, low 8.0%, intermediate/high 5.0%). NT‐proBNP was the strongest mortality predictor across optimal medical therapy (hazard ratio [HR], 1.488 [95% CI, 1.288–1.720], P <0.001), percutaneous coronary intervention (HR, 1.220 [95% CI, 1.020–1.458], P =0.029), and coronary artery bypass grafting (HR, 1.220 [95% CI, 1.049–1.420], P =0.010). Interaction analysis validated a data‐derived 150 pg/mL threshold ( P =0.032): below it, mortality was comparably low regardless of revascularization (HR, 0.98 [95% CI, 0.67–1.43], P =0.910); above it, baseline risk was markedly elevated (HR, 5.75 [95% CI, 4.10–8.00], P <0.001) and revascularization associated with 40% mortality reduction, with substantial residual risk (HR, 3.43 [95% CI, 2.70–4.40], P <0.001). Conclusions HsTnT provides risk factor‐weighted clinical likelihood category‐specific incremental diagnostic value. NT‐proBNP is a universal prognostic marker identifying patients with distinct revascularization‐associated mortality reduction driven by differential baseline risk. Registration URL: https://clinicaltrials.gov/study/NCT00497887 ; Unique Identifier: NCT00497887.