识别缺血性慢性心力衰竭患者 5 年预后的聚类方法

Elena V. Khazova
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A clinical study was conducted, genotyping single nucleotide polymorphisms rs10927875 of the ZBTB17 gene, rs247616 of the CETP gene, rs1143634 of the IL-1β gene, rs1800629 of the TNF gene, rs1800795 of the IL-6 gene was carried out, and patient outcomes were assessed for 5 years. Quantitative data were presented as mean and standard deviation or median and interquartile range; categorical — as frequencies and percentages. Categorical intergroup differences were tested using the χ2 test, and quantitative differences were tested using the Student/Mann–Whitney test. Hierarchical clustering was carried out according to 44 demographic, clinical, genetic variables, time to event was analyzed by the Kaplan–Meier method, risk ratio — by Cox regression. Statistical processing was carried out in the R4.3.1 program. \nRESULTS: Two clusters of patients with heart failure were identified. 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摘要

背景:慢性心力衰竭患者的表型和病理生理学异质性增加了研究人员根据相似的临床和遗传特征进行聚类分析分组的兴趣。目的:通过对临床、器质性和遗传因素进行非对照聚类分析,确定继发于冠心病的慢性心力衰竭患者多变量队列中的表型亚组。材料与方法:研究对象为 470 名功能分级为 I-IV 级、病程稳定、病因为缺血性的慢性心力衰竭患者,男女患者年龄均为 66.4±10.4 岁。进行了临床研究,对 ZBTB17 基因 rs10927875、CETP 基因 rs247616、IL-1β 基因 rs1143634、TNF 基因 rs1800629、IL-6 基因 rs1800795 的单核苷酸多态性进行了基因分型,并对患者 5 年的预后进行了评估。定量数据以均数和标准差或中位数和四分位距表示;分类数据以频率和百分比表示。组间分类差异采用χ2检验,定量差异采用Student/Mann-Whitney检验。根据 44 个人口统计学、临床和遗传变异进行分层聚类,用 Kaplan-Meier 法分析事件发生时间,用 Cox 回归法分析风险比。统计处理在 R4.3.1 程序中进行。结果:确定了两组心力衰竭患者。第 1 组(66%)包括年龄较大的男女患者,主要为功能 III-IV 级慢性心力衰竭,心腔扩大,左心室射血分数降低,心率增快,心房颤动和左心室肥厚。在这个群组中,IL-6 基因 rs1800795 多态性的 GG 基因型(P0.001)和 CETP 基因 rs247616 多态性的 CT 基因型(P=0.014)携带者较多。群组 2(34%)主要由年轻女性组成,代谢指数较高,有心肌梗死和冠状动脉介入治疗史,吸烟,CETP 基因 rs247616 多态性的 TT 基因型比例较大(P=0.029)。结论:研究发现了两个慢性心力衰竭患者群,这两个群的特点是决定各种原因死亡风险的 44 个变量不同。
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Cluster approach to identifying the 5-year prognosis of patients with chronic heart failure of ischemic etiology
BACKGROUND: The phenotypic and pathophysiological heterogeneity of patients with chronic heart failure increases the interest of researchers in grouping according to similar clinical and genetic characteristics based on cluster analysis. AIM: To identify phenotypic subgroups in a multivariate cohort of patients with chronic heart failure secondary to coronary artery disease using uncontrolled cluster analysis of clinical, instrumental and genetic components. MATERIAL AND METHODS: 470 patients with chronic heart failure of functional class I–IV, stable course, ischemic etiology of both sexes at the age of 66.4±10.4 years were examined. A clinical study was conducted, genotyping single nucleotide polymorphisms rs10927875 of the ZBTB17 gene, rs247616 of the CETP gene, rs1143634 of the IL-1β gene, rs1800629 of the TNF gene, rs1800795 of the IL-6 gene was carried out, and patient outcomes were assessed for 5 years. Quantitative data were presented as mean and standard deviation or median and interquartile range; categorical — as frequencies and percentages. Categorical intergroup differences were tested using the χ2 test, and quantitative differences were tested using the Student/Mann–Whitney test. Hierarchical clustering was carried out according to 44 demographic, clinical, genetic variables, time to event was analyzed by the Kaplan–Meier method, risk ratio — by Cox regression. Statistical processing was carried out in the R4.3.1 program. RESULTS: Two clusters of patients with heart failure were identified. Cluster 1 (66%) included older patients of both sexes, predominantly functional class III–IV chronic heart failure, with enlarged heart chambers, reduced left ventricular ejection fraction, higher heart rate, atrial fibrillation and left ventricular hypertrophy. In this cluster, more carriers of the GG genotype of the rs1800795 polymorphism of the IL-6 gene (p 0.001) and the CT genotype of the rs247616 polymorphism of the CETP gene (p=0.014) were identified. Cluster 2 (34%) was represented predominantly by younger women, with a higher metabolic index, a history of myocardial infarction and coronary intervention, smokers, and a larger proportion of the TT genotype of the rs247616 polymorphism of the CETP gene (p=0.029). CONCLUSION: 2 clusters of patients with chronic heart failure, characterized by a different set of 44 variables that determine the risk of death from all causes, were identified.
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