Zhang Zhenyu, Staessen Jan A, Thijs Lutgarde, Gu Yumei, Liu Yanping, Jacobs Lotte, Koeck Thomas, Zürbig Petra, Mischak Harald, Kuznetsova Tatiana
Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium.
Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium; Department of Epidemiology, Maastricht University, Maastricht, Netherlands.
Int J Cardiol. 2014 Sep;176(1):158-65. doi: 10.1016/j.ijcard.2014.07.014. Epub 2014 Jul 12.
In previous studies, we identified two urinary proteomic classifiers, termed HF1 and HF2, which discriminated subclinical diastolic left ventricular (LV) dysfunction from normal. HF1 and HF2 combine information from 85 and 671 urinary peptides, mainly up- or down-regulated collagen fragments. We sought to validate these classifiers in a population study.
In 745 people randomly recruited from a Flemish population (49.8 years; 51.3% women), we measured early and late diastolic peak velocities of mitral inflow (E and A) and mitral annular velocities (e' and a') by conventional and tissue Doppler echocardiography, and the urinary proteome by capillary electrophoresis coupled with mass spectrometry.
In the analyses adjusted for sex, age, body mass index, blood pressure, heart rate, LV mass index and intake of medications, we expressed effect sizes per 1-SD increment in the classifiers. HF1 was associated with 0.204 cm/s lower e' peak velocity (95% confidence interval, 0.057-0.351; p=0.007) and 0.145 higher E/e' ratio (0.023-0.268; p=0.020), while HF2 was associated with a 0.174 higher E/e' ratio (0.046-0.302; p=0.008). According to published definitions, 67 (9.0%) participants had impaired LV relaxation and 96 (12.9%) had elevated LV filling pressure. The odds of impaired relaxation associated with HF1 was 1.38 (1.01-1.88; p=0.043) and that of increased LV filling pressure associated with HF2 was 1.38 (1.00-1.90; p=0.052).
In a general population, the urinary proteome correlated with diastolic LV dysfunction, proving its utility for early diagnosis of this condition.
在先前的研究中，我们识别出两种尿液蛋白质组分类器，分别称为HF1和HF2，它们可区分亚临床舒张期左心室（LV）功能障碍与正常情况。HF1和HF2整合了来自85个和671个尿肽的信息，主要是上调或下调的胶原蛋白片段。我们试图在一项人群研究中验证这些分类器。
在从佛兰芒人群中随机招募的745人（49.8岁；51.3%为女性）中，我们通过传统和组织多普勒超声心动图测量二尖瓣流入的早期和晚期舒张期峰值速度（E和A）以及二尖瓣环速度（e'和a'），并通过毛细管电泳结合质谱法测量尿液蛋白质组。
在针对性别、年龄、体重指数、血压、心率、左心室质量指数和药物摄入量进行调整的分析中，我们表示分类器中每增加1个标准差的效应量。HF1与e'峰值速度降低0.204 cm/s相关（95%置信区间，0.057 - 0.351；p = 0.007）以及E/e'比值升高0.145（0.023 - 0.268；p = 0.020），而HF2与E/e'比值升高0.174相关（0.046 - 0.302；p = 0.008）。根据已发表的定义，67名（9.0%）参与者存在左心室舒张功能受损，96名（12.9%）存在左心室充盈压升高。与HF1相关的舒张功能受损的几率为1.38（1.01 - 1.88；p = 0.043），与HF2相关的左心室充盈压升高的几率为1.38（1.00 - 1.90；p = 0.052）。
在一般人群中，尿液蛋白质组与舒张期左心室功能障碍相关，证明其在该疾病早期诊断中的实用性。
