Left ventricular diastolic function in relation to the urinary proteome: A proof-of-concept study in a general population

Background: 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. Methods: 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. Results: 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). Conclusions: In a general population, the urinary proteome correlated with diastolic LV dysfunction, proving its utility for early diagnosis of this condition.