医学
生物标志物
心力衰竭
射血分数
内科学
射血分数保留的心力衰竭
利钠肽
糖尿病
心脏病学
肌钙蛋白
星团(航天器)
疾病
心肌梗塞
内分泌学
化学
程序设计语言
生物化学
计算机科学
作者
Rebecca J. Woolley,Daan Ceelen,Wouter Ouwerkerk,Jasper Tromp,Sylwia M. Figarska,Stefan D. Anker,Kenneth Dickstein,Gerasimos Filippatos,Faı̈ez Zannad,Marco Metra,Leong L. Ng,Nilesh J. Samani,Dirk J. van Veldhuisen,Chim C. Lang,Carolyn S.P. Lam,Adriaan A. Voors
摘要
The lack of effective therapies for patients with heart failure with preserved ejection fraction (HFpEF) is often ascribed to the heterogeneity of patients with HFpEF. We aimed to identify distinct pathophysiologic clusters of HFpEF based on circulating biomarkers.We performed an unsupervised cluster analysis using 363 biomarkers from 429 patients with HFpEF. Relative differences in expression profiles of the biomarkers between clusters were assessed and used for pathway over-representation analyses. We identified four distinct patient subgroups based on their biomarker profiles: cluster 1 with the highest prevalence of diabetes mellitus and renal disease; cluster 2 with oldest age and frequent age-related comorbidities; cluster 3 with youngest age, largest body size, least symptoms and lowest N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels; and cluster 4 with highest prevalence of ischaemic aetiology, smoking and chronic lung disease, most symptoms, as well as highest NT-proBNP and troponin levels. Over a median follow-up of 21 months, the occurrence of death or heart failure hospitalization was highest in clusters 1 and 4 (62.1% and 62.8%, respectively) and lowest in cluster 3 (25.6%). Pathway over-representation analyses revealed that the biomarker profile of patients in cluster 1 was associated with activation of inflammatory pathways while the biomarker profile of patients in cluster 4 was specifically associated with pathways implicated in cell proliferation regulation and cell survival.Unsupervised cluster analysis based on biomarker profiles identified mutually exclusive subgroups of patients with HFpEF with distinct biomarker profiles, clinical characteristics and outcomes, suggesting different underlying pathophysiological pathways.
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