Urinary proteome analysis in hypertensive patients with left ventricular diastolic dysfunction

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.