目的 探讨替格瑞洛治疗心肌梗死患者血清血管生成素样蛋白3(ANGPTL3)、卷曲螺旋结构域蛋白80(CCDC80)及丝氨酸蛋白酶抑制剂A3(SERPINA3)水平变化与心力衰竭发生的相关性。方法 采用前瞻性研究方法，选取2021年1月—2023年12月南京医科大学第四附属医院收治的338例心肌梗死患者作为研究对象，所有患者均接受替格瑞洛为主的标准化治疗，随访18个月，最终完成随访323例，根据随访期间是否发生心力衰竭分为心力衰竭组（79例）和非心力衰竭组（244例）。比较两组患者基线及治疗后不同时间点血清ANGPTL3、CCDC80、SERPINA3水平，运用单因素及多因素Cox比例风险回归模型分析确定心肌梗死心力衰竭发生的独立危险因素，受试者工作特征（ROC）曲线分析血清ANGPTL3、CCDC80、SERPINA3水平单独及联合检测对风险的预测价值，并采用Spearman等级相关系数分析探讨各指标与心力衰竭的相关性。分析上述指标与心力衰竭发生的相关性及预测价值。结果 323例患者随访18个月期间，79例发生心力衰竭（心力衰竭组），244例未发生心力衰竭（非心力衰竭组）；基线临床资料比较发现，心力衰竭组患者年龄、高血压病史比例、左心室舒张末期内径（LVEDD）、左心室收缩末期内径（LVESD）、N末端B型脑钠肽前体（NT-proBNP）水平均显著高于非心力衰竭组，左室射血分数（LVEF）显著低于非心力衰竭组（P<0.05）；基线时心力衰竭组血清血管生成素样蛋白3(ANGPTL3)、丝氨酸蛋白酶抑制剂A3(SERPINA3)水平显著高于非心力衰竭组，卷曲螺旋结构域蛋白80(CCDC80)水平显著低于非心力衰竭组（均P<0.05）；治疗后6、12、18个月，心力衰竭组血清ANGPTL3、SERPINA3水平持续升高，CCDC80水平持续降低，各时间点与非心力衰竭组比较差异显著（P<0.05）。多因素COX回归分析表明年龄≥65岁[合并风险比（HR）=2.356,95%置信区间（CI）:1.123～4.945,P=0.023]，该年龄段患者心力衰竭发生风险显著升高。NTproBNP升高（HR=2.876,95%CI:1.389～5.956,P=0.005），提示心室壁压力相关指标异常与心力衰竭风险增加密切相关。基线ANGPTL3升高（HR=3.568,95%CI:1.789～7.116,P<0.001），是心力衰竭发生的强风险因子。基线SERPINA3升高（HR=3.012,95%CI:1.506～6.024,P=0.002），其高表达会增加心力衰竭发生概率。ROC曲线分析显示，基线血清ANGPTL3、CCDC80、SERPINA3、年龄、LVEF、NT-proBNP单一指标检测预测心力衰竭的曲线下面积（AUC）分别为0.928、0.907、0.956、0.537、0.736、0.798，联合检测的AUC达0.998显著高于单一指标，且灵敏度（86.49%）、特异度（83.19%）均最优（P<0.05）。相关性分析结果显示，基线血清ANGPTL3、SERPINA3水平与心力衰竭发生呈正相关[相关系数（rs）分别为0.699、0.717,P<0.001]，基线血清CCDC80水平与心力衰竭发生呈负相关（rs=-0.625,P<0.001）。结论 替格瑞洛治疗的心肌梗死患者，血清ANGPTL3、SERPINA3水平升高及CCDC80水平降低与心力衰竭发生密切相关，三者联合检测对心力衰竭的发生具有较高的预测价值，可为临床早期干预提供参考。

Objective To explore the correlation between the changes in serum angiopoietin-like protein 3(ANGPTL3), coil-coil domain protein 80(CCDC80), and serine protease inhibitor A3(SERPINA3) levels in patients with myocardial infarction treated with ticagrelor and the occurrence of heart failure(HF). Methods A prospective cohort study was conducted. A total of 323 patients with myocardial infarction admitted between January 2021 and December 2023 were enrolled as participants. All patients underwent standardized ticagrelor-based therapy with an 18-month follow-up period. Participants were categorized into HF group(79 cases) and non-HF group(244 cases) based on HF occurrence during follow-up. Serum ANGPTL3, CCDC80, and SERPINA3 levels at baseline and post-treatment time points were compared between groups. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify independent risk factors for HF in myocardial infarction patients. Receiver operating characteristic(ROC) curve analysis was employed to evaluate the predictive value of individual and combined serum ANGPTL3, CCDC80, and SERPINA3 levels, while Spearman rank correlation coefficient was used to explore associations between each biomarker and HF. Results During the 18-month follow-up of 323 patients, 79 developed HF(HF group), and 244 did not develop HF(non-HF group). Baseline clinical data comparison revealed that the HF group exhibited significantly higher age, hypertension history proportion, left ventricular end-diastolic diameter(LVEDD), left ventricular end-systolic diameter(LVESD), and N-terminal pro-B-type natriuretic peptide(NT-pro BNP) levels, along with significantly lower left ventricular ejection fraction(LVEF) compared to the non-HF group(P < 0.05). At baseline, ANGPTL3 and SERPINA3 levels were significantly elevated in the HF group, whereas coilcoil domain protein 80(CCDC80) level was significantly reduced compared to the non-HF group(P < 0.05). At 6, 12, and 18 months' post-treatment, the HF group demonstrated progressive increases in serum ANGPTL3 and SERPINA3 levels accompanied by decreases in CCDC80 levels, with significant intergroup differences observed at each time point(P < 0.05). Multivariate Cox regression analysis revealed that patients aged ≥ 65 years(HR = 2.356, 95% CI: 1.123–4.945, P = 0.023) exhibited a significantly elevated risk of HF. Elevated NT-pro BNP(HR = 2.876, 95% CI: 1.389–5.956, P = 0.005) indicates that ventricular wall stress-related biomarkers are independently associated with increased HF risk. Baseline ANGPTL3 elevation(HR = 3.568, 95% CI: 1.789–7.116, P < 0.001) represents an independent risk factor, while elevated baseline SERPINA3(HR = 3.012, 95% CI: 1.506–6.024, P = 0.002) with high baseline levels independently predicting increased HF incidence. Receiver operating characteristic(ROC) curve analysis showed that The area under the curve(AUC) for predicting HF by the single indicators of baseline serum ANGPTL3, CCDC80, SERPINA3, age, LVEF, and NT-pro BNP were 0.928, 0.907, 0.956, 0.537, 0.736, and 0.798, respectively. The AUC of the combined detection reached 0.998, which was significantly higher than that of the single indicator, and the sensitivity(86.49%) and specificity(83.19%) were both the best(P < 0.05). Correlation analysis revealed positive associations between baseline ANGPTL3(r = 0.699, P < 0.001) and SERPINA3 [Spearman's rank correlation coefficient(rs) = 0.717, P < 0.001] levels with HF occurrence, while baseline CCDC80 exhibited a negative correlation(rs =-0.625, P < 0.001). Conclusion In patients with myocardial infarction treated with ticagrelor, elevated levels of serum ANGPTL3 and SERPINA3, as well as decreased levels of CCDC80, are closely related to the occurrence of HF. The combined detection of the three has a high predictive value for the occurrence of HF and can provide a reference for early clinical intervention.

R972

南京市科技计划项目(YZ202216)