HsTnT provides incremental diagnostic value for coronary obstruction inversely proportional to clinical likelihood category, while NT-proBNP is a universal prognostic marker identifying patients with distinct revascularization-associated mortality reduction driven by differential baseline risk in chronic coronary syndrome.
Key Findings
Results
Among five cardiac biomarkers tested, only hsTnT showed meaningful diagnostic capacity for obstructive coronary artery disease.
The study prospectively enrolled 2251 patients undergoing coronary angiography for suspected chronic coronary syndrome with a median follow-up of 12.6 years.
Obstructive coronary artery disease (≥50% stenosis in ≥1 major epicardial vessel) was present in 888 patients (39.4%).
HsTnT achieved an area under the curve (AUC) of 0.669 for diagnosing obstructive CAD.
The risk factor-weighted clinical likelihood (RF-WCL) AUC was 0.663, comparable to hsTnT alone.
The other biomarkers tested were NT-proBNP, high-sensitivity C-reactive protein, interleukin-6, and copeptin.
Results
The incremental diagnostic benefit of hsTnT over clinical likelihood assessment was inversely proportional to the RF-WCL category.
In the very low RF-WCL category, hsTnT provided a ΔAUC of 10.4%.
In the low RF-WCL category, hsTnT provided a ΔAUC of 8.0%.
In the intermediate/high RF-WCL category, hsTnT provided a ΔAUC of 5.0%.
This pattern indicates that hsTnT adds the most diagnostic value in patients who are clinically least likely to have obstructive CAD.
Results
NT-proBNP was the strongest mortality predictor across all three treatment strategies tested.
Under optimal medical therapy, NT-proBNP had a hazard ratio of 1.488 (95% CI, 1.288–1.720), P<0.001.
Under percutaneous coronary intervention (PCI), NT-proBNP had a hazard ratio of 1.220 (95% CI, 1.020–1.458), P=0.029.
Under coronary artery bypass grafting (CABG), NT-proBNP had a hazard ratio of 1.220 (95% CI, 1.049–1.420), P=0.010.
Cox regression with biomarker × treatment interaction testing was used to evaluate these associations.
Results
An NT-proBNP threshold of 150 pg/mL was validated by interaction analysis as a clinically meaningful cut-point for predicting revascularization benefit.
The interaction analysis validated the 150 pg/mL threshold with P=0.032.
Below 150 pg/mL, mortality was comparably low regardless of whether patients received revascularization (HR, 0.98 [95% CI, 0.67–1.43], P=0.910).
Above 150 pg/mL, baseline risk was markedly elevated (HR, 5.75 [95% CI, 4.10–8.00], P<0.001 compared to the low NT-proBNP group).
Above 150 pg/mL, revascularization was associated with approximately 40% mortality reduction, though substantial residual risk remained (HR, 3.43 [95% CI, 2.70–4.40], P<0.001).
The threshold was described as 'data-derived,' indicating it emerged from the dataset rather than being pre-specified.
Results
Patients with NT-proBNP above 150 pg/mL had substantially elevated baseline mortality risk compared to those below the threshold.
The hazard ratio for baseline mortality risk above vs. below the 150 pg/mL NT-proBNP threshold was 5.75 (95% CI, 4.10–8.00), P<0.001.
Even after revascularization, patients above the threshold retained a hazard ratio of 3.43 (95% CI, 2.70–4.40), P<0.001.
This indicates that revascularization attenuates but does not eliminate the excess mortality risk in high NT-proBNP patients.
Methods
The study used a prospective design with long-term follow-up to evaluate both diagnostic and prognostic roles of cardiovascular biomarkers in chronic coronary syndrome.
2251 patients were prospectively enrolled from a registry (ClinicalTrials.gov NCT00497887).
Median follow-up was 12.6 years.
Receiver operating characteristic (ROC) analysis was used for diagnostic evaluation.
Cox regression with biomarker × treatment interaction testing was used for prognostic and treatment-interaction analyses.
Five biomarkers were measured: hsTnT, NT-proBNP, high-sensitivity C-reactive protein, interleukin-6, and copeptin.
What This Means
This research followed over 2,200 patients suspected of having blocked heart arteries for more than 12 years to determine whether common blood tests (biomarkers) can help doctors figure out who actually has significant blockages and who will benefit most from procedures to open those blockages. The study found that a blood test called high-sensitivity troponin T (hsTnT) — a marker of heart muscle stress — was the only one of five biomarkers that meaningfully helped diagnose significant coronary artery blockages, and it was most useful in patients who seemed least likely to have disease based on traditional risk factors. A different biomarker called NT-proBNP, which reflects heart strain, turned out to be the best predictor of long-term survival regardless of how patients were treated.
A key finding was that an NT-proBNP level of 150 pg/mL appeared to be an important dividing line. Patients with levels below this threshold had relatively low death rates whether or not they underwent a procedure to open their arteries, suggesting that revascularization may not add much survival benefit for this group. In contrast, patients with NT-proBNP above 150 pg/mL had dramatically higher death rates overall, but those who received revascularization had about a 40% lower risk of dying compared to those who did not — though they still carried substantially elevated risk compared to the low-biomarker group.
This research suggests that measuring NT-proBNP in patients with chronic coronary artery disease could help identify who is most likely to benefit from procedures like stenting or bypass surgery, and who might do equally well with medication alone. Similarly, hsTnT testing could help doctors decide whether to pursue further testing in patients whose standard risk assessment is inconclusive. These findings point toward a potential role for biomarker-guided decision-making in the management of stable heart artery disease, though further studies would be needed to confirm these thresholds in clinical practice.
Teren A, Netto J, Thiery J, Thiele H, Stellbrink C, Lawin D, et al.. (2026). Cardiac Biomarkers to Refine Pretest Probability for Coronary Obstruction and Predict Survival After Revascularization in Chronic Coronary Syndrome.. Journal of the American Heart Association. https://doi.org/10.1161/JAHA.125.048737