Association between uric acid and cardiac outcomes mediated by neutrophil-to-lymphocyte ratio in patients with left ventricular diastolic dysfunction and pulmonary hypertension

Abstract

To evaluate the association of uric acid (UA) with adverse outcomes and its potential mediator in patients with left ventricular diastolic dysfunction (LVDD) and pulmonary hypertension (PH). We retrospectively analyzed 234 patients with LVDD and PH. The baseline characteristics of patients with low UA (≤ 330 µmol/L) group were compared with high UA (> 330 µmol/L) group. Adverse outcomes included all-cause mortality, cardiac death and heart failure (HF) hospitalization. Their association with UA and the mediator were evaluated using Cox regression and mediation analysis. The mediation proportion was further quantified by the R mediation package. During a mean follow-up of 50 ± 18 months, there were 27 all-cause deaths, 18 cardiovascular deaths and 41 incidents of HF hospitalization. Multivariable Cox regression analysis showed UA was an independent risk factor of adverse outcomes in LVDD and PH patients, even after adjusting for age, sex, body mass index, medical histories, systolic blood pressure, fasting blood glucose, total cholesterol, triglyceride, eGFR, BNP and medications. The hazard ratios (HRs) for UA (per 10 µmol/L increase) were as below: for all-cause mortality, HR 1.143, 95% CI 1.069–1.221, P < 0.001; for cardiac death, HR 1.168, 95% CI 1.064–1.282, P = 0.001; for HF hospitalization, HR 1.093, 95% CI 1.035–1.155, P = 0.001. Neutrophil-to-lymphocyte ratio (NLR) played a partial mediation role in the association, and the mediation proportion for NLR on the UA-adverse outcomes were 21%, 19% and 17%, respectively. In patients of LVDD with PH, higher UA level was independently correlated with adverse outcomes. Furthermore, NLR partially mediated the effect of UA on the risk of all-cause mortality, cardiac death and HF hospitalization.