Studies Coordinating Centre, Division of Hypertension and Cardiovascular Rehabilitation, Department of Cardiovascular Sciences, University of Leuven, Campus Sint Rafaël, Kapucijnenvoer 35, B 3000 Leuven, Belgium.
Eur Heart J. 2012 Sep;33(18):2342-50. doi: 10.1093/eurheartj/ehs185. Epub 2012 Jul 11.
Despite the significant heart failure (HF) burden on society, easily applicable screening techniques, particularly for the early detection of asymptomatic left ventricular (LV) dysfunction, are lacking. The present study aimed to identify and test a set of urinary polypeptides that may indicate early LV diastolic dysfunction as defined by echocardiography in hypertensive patients in a cross-sectional case-control study nested within the FLEMish study on ENvironment, Genes and Health Outcome (FLEMENGHO).
To identify potentially discriminating urinary biomarkers for LV diastolic dysfunction, we applied capillary electrophoresis coupled to mass spectrometry. In the discovery set, we compared 19 hypertensive patients with asymptomatic LV diastolic dysfunction with 19 healthy controls. In the absence of adjustment for multiple testing, 85 urinary peptides were different between cases and controls at a P-value of <0.033. With adjustment for multiple testing, three potential biomarkers remained significantly different between cases and controls (P ≤ 0.02). We combined the 85 potential biomarkers in a high-dimensional model (classifier), which we applied in a blinded manner to an independent test set of 16 hypertensive patients with symptomatic HF and 16 healthy controls. Upon unblinding, the area under the receiver operating characteristic curve (AUC) of the HF classification was 0.84 (95% CI: 0.70-0.98; P= 0.001).
In asymptomatic hypertensive patients with LV diastolic dysfunction, we identified a set of urinary polypeptides specific for essential hypertension with LV diastolic dysfunction that subsequently distinguished hypertensive patients with overt HF from healthy controls.
尽管心力衰竭（HF）给社会带来了巨大负担，但仍缺乏易于应用的筛查技术，尤其是用于早期无症状左心室（LV）功能障碍的筛查技术。本研究旨在通过一项嵌套在 FLEMENGHO 中的 Flemish 环境、基因和健康结果研究（FLEMISH）中的横断面病例对照研究，鉴定和测试一组尿液多肽，这些多肽可能表明高血压患者存在超声心动图定义的早期 LV 舒张功能障碍。
为了鉴定可能用于 LV 舒张功能障碍的潜在有区分性的尿生物标志物，我们应用毛细管电泳与质谱联用技术。在发现组中，我们比较了 19 例无症状 LV 舒张功能障碍的高血压患者和 19 例健康对照者。在未调整多重检验的情况下，病例组和对照组之间有 85 种尿液肽在 P 值<0.033 时有差异。经过多重检验调整后，有 3 种潜在的生物标志物在病例组和对照组之间仍有显著差异（P≤0.02）。我们将 85 种潜在的生物标志物组合成一个高维模型（分类器），并将其以盲法应用于一个包含 16 例有症状 HF 的高血压患者和 16 例健康对照者的独立测试组。在揭盲后，HF 分类的接收器操作特征曲线（ROC）下面积（AUC）为 0.84（95%CI：0.70-0.98；P=0.001）。
在无症状的 LV 舒张功能障碍的高血压患者中，我们鉴定出一组特定于原发性高血压伴 LV 舒张功能障碍的尿液多肽，这些多肽随后将有明显 HF 的高血压患者与健康对照者区分开来。
