Abstract
BACKGROUNDS: Mounting evidences have highlighted the association between metabolites and cardiovascular diseases. Our previous works have demonstrated that circulating metabolite, trimethylamine oxide, was associated with prognosis of patients with pulmonary hypertension (PH). Choline is a precursor of trimethylamine oxide and its role in PH remains unknown. Here, we aimed to validate the hypothesis that circulating choline levels were associated with prognoses in patients with PH. METHODS: Inpatients diagnosed with PH-defined as mean pulmonary arterial pressure ≥ 25 mmHg by right heart catheterisation-from Fuwai Hospital were enrolled after excluding relative comorbidities. Fasting blood samples were obtained to assess choline levels and other clinical variables. The primary endpoints were defined as death, escalation of targeted medication, rehospitalization due to heart failure, PH deterioration. The follow-up duration was defined as the time from the choline examination to the occurrence of outcomes or the end of the study. The associations between circulating choline levels and disease severity and prognoses were explored. RESULTS: Totally, 272 inpatients with PH were enrolled in this study. Patients were divided into high and low choline groups according to the 50(th) quartile of circulating choline levels, defined as 12.6 µM. After confounders adjustment, the high circulating choline levels were still associated with poor World Health Organization functional class, elevated N-terminal pro-B-type natriuretic peptide, and decreased cardiac output index indicating the severe disease condition. Moreover, elevated choline levels were associated with poor prognoses in PH patients even after adjusting for confounders (hazard ratio = 1.934; 95% CI, 1.034-3.619; P = 0.039). Subgroup analyses showed that choline levels predicted the prognosis of patients with pulmonary arterial hypertension but not chronic thromboembolic pulmonary hypertension. CONCLUSIONS: Choline levels were associated with disease severity and poor prognoses of patients with PH, especially in pulmonary arterial hypertension suggesting its potential biomarker role.