Sex-specific evaluation and redevelopment of the GRACE score in non-ST-segment elevation acute coronary syndromes in populations from the UK and Switzerland: a multinational analysis with external cohort validation

Florian A Wenzl; Simon Kraler; Gareth Ambler; Clive Weston; Sereina A Herzog; Lorenz Räber; Olivier Muller; Giovanni G Camici; Marco Roffi; Hans Rickli; Keith A A Fox; Mark de Belder; Dragana Radovanovic; John Deanfield; Thomas F Lüscher

doi:10.1016/S0140-6736(22)01483-0

Sex-specific evaluation and redevelopment of the GRACE score in non-ST-segment elevation acute coronary syndromes in populations from the UK and Switzerland: a multinational analysis with external cohort validation

Lancet. 2022 Sep 3;400(10354):744-756. doi: 10.1016/S0140-6736(22)01483-0. Epub 2022 Aug 29.

Authors

Affiliations

¹ Center for Molecular Cardiology, University of Zürich, Schlieren, Switzerland.
² Department of Statistical Science, University College London, London, UK.
³ Glangwili General Hospital, Carmarthen, UK.
⁴ Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria.
⁵ Department of Cardiology, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland.
⁶ Department of Cardiology, University Hospital of Lausanne, University of Lausanne, Lausanne, Switzerland.
⁷ Center for Molecular Cardiology, University of Zürich, Schlieren, Switzerland; Department of Research and Education, University Hospital Zurich, Zurich, Switzerland.
⁸ Department of Cardiology, University Hospital Geneva, Geneva, Switzerland.
⁹ Cardiology Division, Kantonsspital St Gallen, St Gallen, Switzerland.
¹⁰ Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
¹¹ National Institute for Cardiovascular Outcomes Research, Barts Health NHS Trust, London, UK.
¹² AMIS Plus Data Center, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.
¹³ Institute of Cardiovascular Sciences, University College London, London, UK.
¹⁴ Center for Molecular Cardiology, University of Zürich, Schlieren, Switzerland; Royal Brompton and Harefield Hospitals, London, UK; National Heart and Lung Institute, Imperial College, London, UK; School of Cardiovascular Medicine and Sciences, Kings College London, London, UK. Electronic address: cardio@tomluescher.ch.

PMID: 36049493
DOI: 10.1016/S0140-6736(22)01483-0

Abstract

Background: The Global Registry of Acute Coronary Events (GRACE) 2.0 score was developed and validated in predominantly male patient populations. We aimed to assess its sex-specific performance in non-ST-segment elevation acute coronary syndromes (NSTE-ACS) and to develop an improved score (GRACE 3.0) that accounts for sex differences in disease characteristics.

Methods: We evaluated the GRACE 2.0 score in 420 781 consecutive patients with NSTE-ACS in contemporary nationwide cohorts from the UK and Switzerland. Machine learning models to predict in-hospital mortality were informed by the GRACE variables and developed in sex-disaggregated data from 386 591 patients from England, Wales, and Northern Ireland (split into a training cohort of 309 083 [80·0%] patients and a validation cohort of 77 508 [20·0%] patients). External validation of the GRACE 3.0 score was done in 20 727 patients from Switzerland.

Findings: Between Jan 1, 2005, and Aug 27, 2020, 400 054 patients with NSTE-ACS in the UK and 20 727 patients with NSTE-ACS in Switzerland were included in the study. Discrimination of in-hospital death by the GRACE 2.0 score was good in male patients (area under the receiver operating characteristic curve [AUC] 0·86, 95% CI 0·86-0·86) and notably lower in female patients (0·82, 95% CI 0·81-0·82; p<0·0001). The GRACE 2.0 score underestimated in-hospital mortality risk in female patients, favouring their incorrect stratification to the low-to-intermediate risk group, for which the score does not indicate early invasive treatment. Accounting for sex differences, GRACE 3.0 showed superior discrimination and good calibration with an AUC of 0·91 (95% CI 0·89-0·92) in male patients and 0·87 (95% CI 0·84-0·89) in female patients in an external cohort validation. GRACE 3·0 led to a clinically relevant reclassification of female patients to the high-risk group.

Interpretation: The GRACE 2.0 score has limited discriminatory performance and underestimates in-hospital mortality in female patients with NSTE-ACS. The GRACE 3.0 score performs better in men and women and reduces sex inequalities in risk stratification.

Funding: Swiss National Science Foundation, Swiss Heart Foundation, Lindenhof Foundation, Foundation for Cardiovascular Research, and Theodor-Ida-Herzog-Egli Foundation.

MeSH terms

Acute Coronary Syndrome* / diagnosis
Acute Coronary Syndrome* / therapy
Female
Hospital Mortality
Humans
Male
Prognosis
Registries
Risk Assessment
Switzerland / epidemiology
United Kingdom