Sex inequities in the performance of the GRACE 2.0 score in non-ST-segment elevation acute coronary syndromes: a multinational observational study in contemporary cohorts from four European countries
Authors: Wenzl F , Kraler S , Weston C , Ambler G , Raeber L , Muller O , Paneni F , Camici G G , Puhan M A , Roffi M , Rickli H , De Belder M , Radovanovic D , Deanfield J , Luescher T F 
Published: October 2022

Abstract

Background
The Global Registry of Acute Coronary Events (GRACE) score was developed and validated in predominantly male patient populations. Growing evidence indicates distinct pathophysiologic and clinical characteristics of non-ST-segment elevation acute coronary syndromes (NSTE-ACS) in women and men.

Purpose
We aimed to assess sex differences in the performance of the GRACE score in NSTE-ACS in contemporary populations.

Methods
We calculated GRACE 2.0 risk estimates for patients with NSTE-ACS in contemporary nation-wide ACS cohorts from England, Wales, and Northern Ireland (MINAP, 2005–2017, n=400,054) and from Switzerland (AMIS Plus, 2005–2020, n=20,727; SPUM-ACS, 2009–2017, n=2,239). Sex disaggregated analyses were stratified according to the mortality endpoint of the score (in-hospital death, death at 6 months, death at 1 year), the clinical setting (calculated at admission and calculated for hospital survivors, respectively), the geographic region (United Kingdom and Switzerland, respectively) and the level of care (all hospitals and PCI-capable university hospitals, respectively). The area under the receiver operating characteristic curve (AUC), the average prediction error (APE), and the misclassification rate (MCR) were compared between women and men.

Results
The discriminatory performance of GRACE 2.0 for in-hospital death was lower and the APE and MCR were higher in women as compared to men in the United Kingdom (AUC female: 80.4%, 95% confidence interval [CI], 80.0 to 80.8, AUC male: 84.7%, 95% CI, 84.4 to 85.1, p&lt;0.001; APE female: 0.0512, 95% CI, 0.0501–0.0522, APE male: 0.0357, 95% CI, 0.0351 to 0.0363; MCR female: 5.81%, 95% CI, 5.68 to 5.94, MCR male: 3.96, 95% CI, 3.89 to 4.03) and in Switzerland (AUC female: 84.2%, 95% CI, 81.4 to 86.8, AUC male: 88.5%, 95% CI 87.1–89.7, p=0.003; APE female: 0.0420, 95% CI 0.0376 to 0.0465, APE male: 0.0312, 95% CI 0.0289 to 0.0335; MCR female: 4.98%, 95% CI 4.39 to 5.56, MCR male: 3.69%, 95% CI, 3.39 to 4.00). Similar results were obtained for 6-month death and 1-year death endpoints across clinical settings, geographic regions, and levels of care. The risk of in-hospital death relative to males was increased in females that GRACE 2.0 classified as low-to-intermediate risk (suggesting no early invasive management strategy) in the United Kingdom (relative risk [RR]: 1.61, 95% CI, 1.50 to 1.74, p&lt;0.001) and in Switzerland (RR: 1.84, 95% CI, 1.28 to 2.64, p&lt;0.001).

Conclusion
Thus far, this is the largest investigation on the GRACE risk score. We confirmed good overall score performance and found decreased performance in contemporary female patients with NSTE-ACS irrespective of the mortality endpoint, the clinical setting, the geographic region, and the level of care.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swiss National Science FoundationSwiss Heart Foundation