Expanding the modified GRACE risk score to high-sensitivity troponin i: a multinational validation cohort study
D Delialis, G Georgiopoulos, C Konstantaki, L Spray, S Kraler, P Nastatos, P Manifava, S F Giannakopoulou, Y Skoumas, C Pitsavos, M A Dimopoulou, K Stellos, I Spyridopoulos, D Panagiotakos, K StamatelopoulosAbstract
The GRACE 2.0 risk score is a widely used tool for estimating mortality in patients with acute coronary syndrome (ACS). However, it incorporates high-sensitivity troponin (hs-Tn) as a binary variable (elevated vs. non-elevated), which may limit its prognostic precision in contemporary practice. While a modified GRACE (modGRACE) model using continuous hs-troponin T (hs-TnT) has shown superior performance, evidence regarding its efficacy using continuous hs-troponin I (hs-TnI) is limited. This study aimed to validate the modGRACE score using continuous hs-TnI across two independent ACS cohorts.
Data were analyzed from two prospective studies: the Freeman cohort (Newcastle, UK) and the GREECS cohort (Athens, Greece). The modGRACE score was calculated by substituting continuous hs-TnT with continuous hs-TnI using previously established regression coefficients. Predictive performance was evaluated by comparing the area under the receiver operating characteristic curve (AUC) and net reclassification improvement (NRI) for short-term (in-hospital, 30-day) and long-term (up to 20-year) outcomes.
In the Freeman cohort, modGRACE demonstrated modest improvements in discrimination for in-hospital mortality (AUC 0.884 vs. 0.870) and 30-day mortality (AUC 0.883 vs. 0.868). A significant improvement in discrimination was observed for 1-year mortality (ΔAUC 0.015, p=0.01). Furthermore, risk reclassification was significantly improved for in-hospital (NRI=0.67), 30-day (NRI=0.69), and 1-year mortality (NRI=0.49; all p<0.001).
In the GREECS cohort, modGRACE significantly improved risk reclassification for 30-day mortality (NRI=0.56), 20-year cardiovascular mortality (NRI=0.85), and 20-year Major Adverse Cardiovascular Events (MACE; NRI=0.79; all p<0.001).
Integrating continuous hs-TnI into the modGRACE score leads to consistent and clinically meaningful improvements in risk reclassification compared to the standard GRACE 2.0 score. These findings support the clinical implementation of modGRACE for long-term risk stratification in ACS patients, regardless of whether hs-TnT or hs-TnI assays are utilized. Improved risk reclassification may help clinicians better tailor follow-up intensity and secondary prevention strategies.ROC curves for GRACE vs modGRACEReclassification value of modGRACE vs GRACE