Incremental prognostic value of a cardio-renal-inflammatory biomarker triad for early mortality prediction in acute coronary syndromes

Background

High-sensitivity cardiac troponin I (hs-cTnI) is the cornerstone biomarker for diagnosing myocardial injury and risk stratification in acute coronary syndromes (ACS). However, troponin reflects myocardial necrosis and does not capture other major pathophysiological pathways influencing prognosis. Systemic inflammation and renal dysfunction are key determinants of adverse outcomes in ACS and may provide complementary prognostic information beyond myocardial injury alone.

Purpose

To assess the incremental prognostic value of a multimarker strategy integrating hs-cTnI, C-reactive protein (CRP), and creatinine for early prediction of in-hospital mortality in patients presenting with ACS.

Methods

This prospective cohort study included 2,567 consecutive adults admitted with ACS between January 2023 and June 2025. Biomarkers were measured at emergency department presentation.

Prespecified thresholds were hs-cTnI ≥17.5 µg/L, CRP >6 mg/L, and renal injury defined as creatinine >11 mg/L and/or urea >0.36 g/L.

Clinical variables including symptom-to-admission delay and left ventricular ejection fraction (LVEF) were recorded and incorporated into multivariable models.

The primary endpoint was all-cause in-hospital mortality. Independent predictors were identified using multivariable logistic regression. Model discrimination was evaluated using the area under the receiver-operating characteristic curve (AUC), calibration was assessed using calibration intercept and slope, and clinical usefulness was examined using decision-curve analysis. Internal validation was performed using bootstrap resampling (1,000 iterations).

Results

The median age was 61 years (interquartile range 44–71), and 55% were men. In-hospital mortality occurred in 503 patients (19.6%).

In multivariable analysis, all three biomarkers were independently associated with mortality:hs-cTnI ≥17.5 µg/L (OR 2.61, 95% CI 2.04–3.35; p<0.001)CRP >6 mg/L (OR 1.85, 95% CI 1.42–2.41; p<0.001)renal injury (OR 2.33, 95% CI 1.76–3.07; p<0.001)

Compared with hs-cTnI alone, the multimarker model provided significant incremental prognostic discrimination for in-hospital mortality (AUC 0.71 vs 0.65; p<0.001) and demonstrated excellent calibration (calibration slope 0.99).

Decision-curve analysis showed a consistent net clinical benefit across predicted risk thresholds between 10% and 50%, supporting the clinical utility of the multimarker approach.

Conclusion

A multimarker strategy integrating hs-cTnI, CRP, and creatinine significantly improves early mortality prediction in ACS compared with troponin alone. By simultaneously capturing myocardial injury, systemic inflammation, and cardio-renal dysfunction, this simple and widely available biomarker triad enhances early risk stratification and may support rapid triage and risk-guided management in patients presenting with acute coronary syndromes.ROC curves hs-cTnI vs triad model in ACS