Supplementary Material for: Serum Human epididymis protein 4 as a prognostic predictor of new onset heart failure among women after acute coronary syndrome: a single-center retrospective study

Introduction: Little is known about the prognostic factors among women with acute coronary syndrome (ACS), partly due to the small number of women included in heart failure (HF) clinical trials. Human epididymis protein 4 (HE4) has been proven to be a new biomarker for acute and chronic HF over the years. We hypothesize that HE4 could be a promising predictor. Methods: This retrospective study analyzed data from Zhejiang Provincial People’s Hospital. This study included 302 female patients with ACS between January 1, 2021, and December 1, 2021. The primary outcome was new-onset HF after ACS during the 12-month follow-up period. We used a logistic regression model to evaluate the association between serum HE4 levels and the incidence of HF. Serum HE4 levels were measured at baseline (within 24 hours after admission). Results: Of the 302 female patients, 70 (23.2 %) developed new-onset HF within 12 months. Serum HE4 levels in patients with adverse events were significantly higher than those in patients without events (8.9 (7.3-11.5) pmol/dL vs. 5.9 (5.0-6.8) pmol/dL, P < 0.001). The levels of HE4, troponin I peak, left ventricular ejection fraction (LVEF), and estimated glomerular filtration rate (eGFR) were validated as independent predictors, with HE4 being the best laboratory predictor (area under the curve, 0.863; 95 % confidence interval, 0.817-0.909). Serum HE4 concentrations of > 6.93 pmol/dL distinguished patients at risk of HF with 82.9 % sensitivity and 78.0 % specificity (maximum Youden index J, 0.609). Moreover, HE4 levels were associated with an increased risk of HF. Discussion/Conclusion: We found a strong relationship between HE4 and the occurrence of HF after ACS among women, which might help identify patients at high risk of HF for whom close or intense management should be mandatory.

引言：目前对于急性冠状动脉综合征（ACS）女性患者的预后影响因素尚缺乏深入了解，部分原因在于心力衰竭（HF）临床试验中纳入的女性受试者数量较少。多年来，人附睾蛋白4（HE4）已被证实为急性与慢性HF的新型生物标志物。本研究假设HE4可作为一项具有应用前景的预测指标。
方法：本项回顾性研究分析了浙江省人民医院的临床数据，纳入2021年1月1日至2021年12月1日期间收治的302例ACS女性患者。本研究的主要结局为随访12个月期间ACS术后新发HF事件。采用logistic回归模型评估血清HE4水平与HF发生率之间的关联，血清HE4水平于基线时（入院24小时内）进行检测。
结果：在302例女性患者中，70例（23.2%）在随访12个月内出现新发HF。发生不良事件的患者血清HE4水平显著高于未发生事件者[8.9（7.3~11.5）pmol/dL vs. 5.9（5.0~6.8）pmol/dL，P<0.001]。HE4水平、肌钙蛋白I峰值、左心室射血分数（LVEF）及估算肾小球滤过率（eGFR）被证实为独立预测因素，其中HE4为最优实验室检测预测指标（曲线下面积为0.863；95%置信区间为0.817~0.909）。当血清HE4浓度>6.93 pmol/dL时，可识别HF高危患者，其灵敏度为82.9%，特异度为78.0%（最大尤登指数J为0.609）。此外，HE4水平与HF发病风险升高呈显著相关。
讨论与结论：本研究发现，女性ACS患者的血清HE4水平与ACS术后HF发生存在显著关联，该发现有助于识别HF高危人群，对这类患者应实施密切强化的临床管理。