Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
Mosaiques Diagnostic and Therapeutics AG, Hannover, Germany.
Proteomics Clin Appl. 2019 Mar;13(2):e1800174. doi: 10.1002/prca.201800174. Epub 2019 Feb 18.
Diastolic heart failure (DHF) is characterized by slow left ventricular (LV) relaxation, increased LV stiffness, interstitial deposition of collagen, and a modified extracellular matrix proteins. Among Europeans, the frequency of asymptomatic diastolic LV dysfunction (DD) is 25%. This constitutes a large pool of people at high risk of DHF. The goal of this review was to describe the discovery and the initial validation of new multidimensional urinary peptidomic biomarkers (UPB) indicative of DD, mainly consisting of collagen fragments, and to describe a roadmap for their introduction into clinical practice. The availability of new drugs creates a window of opportunity for mounting a randomized clinical trial consolidating the clinical applicability of UPB to screen for DD. If successfully completed, such trial will benefit ≈25% of all people older than 50 years and open a large market for a UPB diagnostic tool and the drug tested. Moreover, sequenced peptides making up UPB will generate novel insights in the pathophysiology of DD and facilitate personalized treatment of patients with DHF for whom prevention came too late. If proven cost-effective, the clinical application of UPB will contribute to the sustainability of health care in aging population in epidemiologic transition.
舒张性心力衰竭（DHF）的特征为左心室（LV）松弛缓慢、LV 僵硬度增加、间质胶原沉积和细胞外基质蛋白改变。在欧洲人群中，无症状舒张性左心室功能障碍（DD）的频率为 25%。这构成了一个高危 DHF 人群的庞大基数。本综述旨在描述新的多维尿肽组学生物标志物（UPB）的发现和初步验证，这些标志物主要由胶原片段组成，提示存在 DD，并描述其引入临床实践的路线图。新型药物的出现为开展随机临床试验提供了机会，该临床试验旨在整合 UPB 的临床适用性，以筛查 DD。如果试验成功，将使所有 50 岁以上人群中的 ≈25%获益，并为 UPB 诊断工具和所测试药物打开广阔的市场。此外，构成 UPB 的序列肽将为 DD 的病理生理学提供新的见解，并有助于对 DHF 患者进行个体化治疗，因为对于这些患者来说，预防为时已晚。如果被证明具有成本效益，UPB 的临床应用将有助于老龄化人口在流行病学转变过程中保持医疗保健的可持续性。
