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. 2023 Oct 1;8(10):946-956.
doi: 10.1001/jamacardio.2023.2741.

Modification of the GRACE Risk Score for Risk Prediction in Patients With Acute Coronary Syndromes

Georgios Georgiopoulos  1   2   3 , Simon Kraler  4 , Matthias Mueller-Hennessen  5   6 , Dimitrios Delialis  1 , Georgios Mavraganis  1 , Kateryna Sopova  2   6   7   8   9 , Florian A Wenzl  4 , Lorenz Räber  10 , Moritz Biener  5 , Barbara E Stähli  11 , Eleni Maneta  1 , Luke Spray  9 , Juan F Iglesias  12 , Jose Coelho-Lima  2 , Simon Tual-Chalot  13 , Olivier Muller  14 , François Mach  12 , Norbert Frey  5   6 , Daniel Duerschmied  6   7   15 , Harald F Langer  6   7   15 , Hugo Katus  5   6 , Marco Roffi  12 , Giovanni G Camici  4 , Christian Mueller  16 , Evangelos Giannitsis  5 , Ioakim Spyridopoulos  2   9 , Thomas F Lüscher  4   17 , Konstantinos Stellos  6   7   8   13 , Kimon Stamatelopoulos  1   2
Affiliations

Modification of the GRACE Risk Score for Risk Prediction in Patients With Acute Coronary Syndromes

Georgios Georgiopoulos et al. JAMA Cardiol. .

Erratum in

  • Corrected to Open Access Status.
    [No authors listed] [No authors listed] JAMA Cardiol. 2024 Jan 1;9(1):95. doi: 10.1001/jamacardio.2023.4300. JAMA Cardiol. 2024. PMID: 37938826 Free PMC article. No abstract available.

Abstract

Importance: The Global Registry of Acute Coronary Events (GRACE) risk score, a guideline-recommended risk stratification tool for patients presenting with acute coronary syndromes (ACS), does not consider the extent of myocardial injury.

Objective: To assess the incremental predictive value of a modified GRACE score incorporating high-sensitivity cardiac troponin (hs-cTn) T at presentation, a surrogate of the extent of myocardial injury.

Design, setting, and participants: This retrospectively designed longitudinal cohort study examined 3 independent cohorts of 9803 patients with ACS enrolled from September 2009 to December 2017; 2 ACS derivation cohorts (Heidelberg ACS cohort and Newcastle STEMI cohort) and an ACS validation cohort (SPUM-ACS study). The Heidelberg ACS cohort included 2535 and the SPUM-ACS study 4288 consecutive patients presenting with a working diagnosis of ACS. The Newcastle STEMI cohort included 2980 consecutive patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention. Data were analyzed from March to June 2023.

Exposures: In-hospital, 30-day, and 1-year mortality risk estimates derived from an updated risk score that incorporates continuous hs-cTn T at presentation (modified GRACE).

Main outcomes and measures: The predictive value of continuous hs-cTn T and modified GRACE risk score compared with the original GRACE risk score. Study end points were all-cause mortality during hospitalization and at 30 days and 1 year after the index event.

Results: Of 9450 included patients, 7313 (77.4%) were male, and the mean (SD) age at presentation was 64.2 (12.6) years. Using continuous rather than binary hs-cTn T conferred improved discrimination and reclassification compared with the original GRACE score (in-hospital mortality: area under the receiver operating characteristic curve [AUC], 0.835 vs 0.741; continuous net reclassification improvement [NRI], 0.208; 30-day mortality: AUC, 0.828 vs 0.740; NRI, 0.312; 1-year mortality: AUC, 0.785 vs 0.778; NRI, 0.078) in the derivation cohort. These findings were confirmed in the validation cohort. In the pooled population of 9450 patients, modified GRACE risk score showed superior performance compared with the original GRACE risk score in terms of reclassification and discrimination for in-hospital mortality end point (AUC, 0.878 vs 0.780; NRI, 0.097), 30-day mortality end point (AUC, 0.858 vs 0.771; NRI, 0.08), and 1-year mortality end point (AUC, 0.813 vs 0.797; NRI, 0.056).

Conclusions and relevance: In this study, using continuous rather than binary hs-cTn T at presentation, a proxy of the extent of myocardial injury, in the GRACE risk score improved the mortality risk prediction in patients with ACS.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Kraler reported grants from the Jubiläumsstiftung SwissLife, the Theodor-Ida-Herzog-Egli Foundation, Lindenhof Foundation, and Novartis Foundation for Medical-Biological Research during the conduct of the study; grants from the Swiss Heart Foundation, European Atherosclerosis Society, European Society of Clinical Investigation, Sphingotec, 4TEEN4 Pharmaceuticals, PAM Theragnostics, and European Society of Cardiology; and nonfinancial support from Roche Diagnostics outside the submitted work. Dr Müller-Hennessen reported grants from Roche Diagnostics and Thermo Scientific as well as personal fees from Zoll CMS outside the submitted work. Dr Wenzl reported support for the SPUM-ACS registry from the Swiss National Science Foundation, Swiss Heart Foundation, Roche Diagnostics, Eli Lilly, AstraZeneca, Medtronic, Merck Sharpe and Dohme, Sanofi-Aventis, and St Jude Medical AG during the conduct of the study; and support from the FAN Foundation of the University of Zurich, Sphingotec, 4TEEN4 Pharmaceuticals, and PAM Theragnostics outside the submitted work. Dr Räber reported grants from Abbott, Boston Scientific, Heartflow, Infraredx, Sanofi, and Regeneron as well as personal fees from Abbott, Amgen, AstraZeneca, Biotronik, Canon, Occlutech, NovoNordisk, and Medtronic outside the submitted work. Dr Biener reported grants from AstraZeneca outside the submitted work. Dr Stähli reported support from the H.H. Sheikh Khalifa bin Hamad Al-Thani Research Programme; grants from the OPO Foundation, the Iten-Kohaut Foundation, the German Center for Cardiovascular Research (DZHK), the German Heart Research Foundation, the B. Braun Foundation, Boston Scientific, and Edwards Lifesciences; and personal fees from Boston Scientific, Abbott Vascular, and MedAlliance. Dr Iglesias reported grants from Biotronik, Abbott Vascular, AstraZeneca, Biosensors, Concept Medical, Philips Volcano, and Terumo Corp as well as personal fees from AstraZeneca, Biotronik, Biosensors, Bristol Myers Squibb/Pfizer, Cordis, Concept Medical, Biosensors, Medalliance, Novartis, Medtronic, Terumo Corp., and Philips Volcano outside the submitted work. Dr Muller reported honoraria from Novartis, Abbott, and Edwards Lifesciences as well as research grant from Edwards Lifesciences. Dr Mach reported research grants to the institution from Amgen, AstraZeneca, Boston Scientific, Biotronik, Eli Lilly, Medtronic, Merck Sharp & Dohme, and St Jude Medical. Dr Frey reported personal fees from Boehringer Ingelheim, AstraZeneca, Bayer, and Pfizer outside the submitted work. Dr Duerschmied reported research grants from the German Research Foundation (DFG) and the German Center for Cardiovascular Research (DZHK) as well as personal fees from Bayer, Daiichi Sankyo, Boehringer Ingelheim, AstraZeneca, and Boston Scientific outside the submitted work. Dr Roffi reported grants from Terumo, Boston Scientific, Biotronik, Medtronic, and Cordis/Cardinal Health outside the submitted work. Dr Camici reported personal fees from Sovida outside the submitted work and is co-inventor on the International Patent WO/2020/226993. Dr Mueller has received research support paid to the institution from the Swiss National Science Foundation, Swiss Heart Foundation, University Hospital Basel, University of Basel, Abbott, AstraZeneca, Beckman Coulter, Boehringer Ingelheim, Brahms, Idorsia, LSI Medience Corporation, Novartis, Ortho Diagnostics, Quidel, Roche, Siemens, Singulex, Sphingotec, and SpinChip as well as personal fees paid to the institution from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Idorsia, Novartis, Osler, Roche, SpinChip, and Sanofi outside the submitted work. Dr Giannitsis reported grants from Roche Diagnostics as well as personal fees from AstraZeneca, BayerVital, Daiichi Sankyo, Roche Diagnostics, Boehringer Ingelheim, and Brahms Deutschland outside the submitted work. Dr Spyridopoulos reported grants from Kancera and AstraZeneca outside the submitted work. Dr Lüscher reported grants from Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Novartis, and Vifor and consulting fees from Daiichi Sankyo, Ineeo Inc, Philipps, and Pfizer outside the submitted work; and holds leadership positions at the European Society of Cardiology, Swiss Heart Foundation, and the Foundation for Cardiovascular Research—Zurich Heart House. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flowchart of the Study
The derivation cohort was composed of 2 cohorts: (1) patients presenting to the emergency department (ED) of Heidelberg University Hospital, Heidelberg, Germany, with a working diagnosis of acute coronary syndrome (ACS) from June 2009 to April 2014, as previously described,, and (2) consecutive patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention admitted to the Freeman Hospital, Newcastle upon Tyne, UK, between June 2010 and December 2014, as previously described. The external validation cohort was based on the SPUM-ACS study, an investigator-initiated, multicenter prospective cohort study that enrolled patients with ACS from December 2009 to December 2017 in Switzerland, as previously described. GRACE indicates Global Registry of Acute Coronary Events; hs-cTn, high-sensitivity cardiac troponin.
Figure 2.
Figure 2.. Discrimination Value of the Modified Global Registry of Acute Coronary Events (GRACE) Risk Score Compared With the Original and Calibrated GRACE Risk Scores for 30-Day Mortality
Nelson-Aalen plots for low-risk, intermediate-risk, and high-risk patients for 30-day mortality as classified by the original and calibrated GRACE risk scores. Note that lines show discrimination of low-risk, intermediate-risk, and high-risk patients by the calibrated GRACE score using prognostic (ie, continuous) instead of diagnostic (ie, less than or greater than 14 ng/L) high-sensitivity cardiac troponin T concentrations at acute coronary syndrome (ACS) presentation. A, A total of 72 of 2692 patients with ACS classified as low risk by the original GRACE score presented with higher observed risk by the modified GRACE score. B, A total of 2406 of 3212 patients with ACS classified as intermediate risk by the original GRACE score presented at lower observed risk and 71 at higher observed risk by the modified GRACE score. C, A total of 2251 of 3473 patients with ACS originally classified as high risk presented at lower observed risk by the modified GRACE score. D, A total of 237 of 5853 patients with ACS classified as low risk by the calibrated GRACE score presented with observed higher risk by the modified GRACE score. E, A total of 366 of 2070 patients with ACS classified as intermediate risk by the calibrated GRACE score presented at lower observed risk and 53 at higher observed risk by the modified GRACE score. F, A total of 214 of 1418 patients with ACS classified by the calibrated GRACE score as high risk presented at lower observed risk by the modified GRACE score.
See this image and copyright information in PMC

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