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,The Lancet

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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
The Lancet ( IF 98.4 ) Pub Date : 2022-08-29 , DOI: 10.1016/s0140-6736(22)01483-0
Florian A Wenzl ₁ , Simon Kraler ₁ , Gareth Ambler ₂ , Clive Weston ₃ , Sereina A Herzog ₄ , Lorenz Räber ₅ , Olivier Muller ₆ , Giovanni G Camici ₇ , Marco Roffi ₈ , Hans Rickli ₉ , Keith A A Fox ₁₀ , Mark de Belder ₁₁ , Dragana Radovanovic ₁₂ , John Deanfield ₁₃ , Thomas F Lüscher ₁₄

Affiliation

Center for Molecular Cardiology, University of Zürich, Schlieren, Switzerland.
Department of Statistical Science, University College London, London, UK.
Glangwili General Hospital, Carmarthen, UK.
Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria.
Department of Cardiology, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland.
Department of Cardiology, University Hospital of Lausanne, University of Lausanne, Lausanne, Switzerland.
Center for Molecular Cardiology, University of Zürich, Schlieren, Switzerland; Department of Research and Education, University Hospital Zurich, Zurich, Switzerland.
Department of Cardiology, University Hospital Geneva, Geneva, Switzerland.
Cardiology Division, Kantonsspital St Gallen, St Gallen, Switzerland.
Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
National Institute for Cardiovascular Outcomes Research, Barts Health NHS Trust, London, UK.
AMIS Plus Data Center, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.
Institute of Cardiovascular Sciences, University College London, London, UK.
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.

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.

中文翻译：

英国和瑞士人群非 ST 段抬高急性冠脉综合征 GRACE 评分的性别特异性评估和重建：一项具有外部队列验证的多国分析

背景

全球急性冠状动脉事件登记处 (GRACE) 2.0 评分是在以男性为主的患者群体中开发和验证的。我们的目的是评估其在非 ST 段抬高急性冠状动脉综合征 (NSTE-ACS) 中的性别特异性表现，并开发一种改进的评分 (GRACE 3.0)，以解释疾病特征的性别差异。

方法

我们评估了来自英国和瑞士的当代全国队列中 420781 名连续 NSTE-ACS 患者的 GRACE 2.0 评分。预测院内死亡率的机器学习模型由 GRACE 变量提供信息，并根据来自英格兰、威尔士和北爱尔兰的 386 591 名患者的按性别分类的数据开发（分为 309 083 [80·0%] 名患者的训练队列）和 77 508 [20·0%] 患者的验证队列）。对来自瑞士的 20727 名患者进行了 GRACE 3.0 评分的外部验证。

发现

2005 年 1 月 1 日至 2020 年 8 月 27 日期间，英国的 400 054 名 NSTE-ACS 患者和瑞士的 20 727 名 NSTE-ACS 患者被纳入研究。GRACE 2.0 评分对住院死亡的区分在男性患者中表现良好（接受者操作特征曲线下面积 [AUC] 0·86，95% CI 0·86–0·86），而在女性患者中明显较低（0 ·82, 95% CI 0·81–0·82；p<0·0001)。GRACE 2.0 评分低估了女性患者的院内死亡风险，倾向于将她们错误地分层为低至中等风险组，而该评分并不表明早期有创治疗。考虑到性别差异，GRACE 3.0 显示出更好的辨别力和良好的校准，男性患者的 AUC 为 0·91 (95% CI 0·89–0·92)，男性患者为 0·87 (95% CI 0·84–0·89) ) 在外部队列验证中的女性患者中。