High Betaine and Dynamic Increase of Betaine Levels Are Both Associated With Poor Prognosis of Patients With Pulmonary Hypertension

Abstract

Background and ObjectiveThe association between plasma betaine levels and cardiovascular diseases (CVDs) has been revealed except for pulmonary hypertension (PH). In this study, we aimed to explore the role of betaine in patients with PH.MethodsInpatients with PH at Fuwai Hospital were enrolled after excluding relative comorbidities. Each patient received at least one follow-up through a clinical visit, and the fasting blood was obtained both at the first and second hospitalization for betaine detection. The primary endpoint was defined as composite outcome events and the mean duration was 14.3 (6.9, 21.3) months. The associations of betaine and changes of betaine (Δbetaine) with disease severity and prognosis were explored.ResultsFinally, a total of 216 patients with PH were included and the medians for betaine plasma levels in the total patients group, low betaine, and high betaine groups were 49.8 (39.0, 68.3) μM, 39.0 (33.5, 44.7) μM, and 68.1 (57.8, 88.7) μM, respectively. High betaine was associated with poor World Health Organization Functional Class (WHO-FC), increased N-terminal pro-brain natriuretic peptide (NT-proBNP), low tricuspid annular plane systolic excursion (TAPSE), and cardiac output index even after adjusting for confounders. Patients with high betaine were over twice the risk to receive the poor prognosis than those with a low level [hazard ratio (HR) = 2.080, (95% CI: 1.033–4.188)]. Moreover, the decrease of betaine level after further treatment was positively correlated to ΔNT-proBNP indicating Δbetaine might be an effector of disease severity, and dynamic increase of betaine was also associated with poor prognosis in PH.ConclusionBetaine was associated with disease severity and might be an effector in PH. Patients with increased levels or with dynamic rise of betaine heralded a poor prognosis.

Circulating choline levels are associated with prognoses in patients with pulmonary hypertension: a cohort study

“…There is increasing interest in the potential role of metabolism in the initiation and progression of PH as studies have suggested the presence of metabolic disturbances in patients with PH [ 6 ]. Our previous work also revealed that aberrant metabolism, characterised by elevated plasma TMAO and betaine levels, is associated with greater disease severity and worse prognoses in patients with PH and may serve as potential surrogate biomarkers for PH [ 7 – 9 ]. Choline—a precursor of TMAO—is a critical micronutrient that participates in various physiological processes, and it serves as an independent predictor of various cardiovascular disorders, such as hypertension [ 10 ], atherosclerosis [ 11 ], and myocardial infarction [ 12 ].…”

Betaine—The dark knight of the brain

“…80 The excess of betaine has been associated with cardiovascular disease and pulmonary hypertension. 81,82 While there are very few side effects recorded for betaine, 83,84 there is still not enough information on the long-term effects of regular betaine supplementation.…”

“…The reported side effects (for 6–9 g/day) are relatively mild such as gastrointestinal illness, mild body odour, increased urination, feeling dry mouth and preference for salty food 80 . The excess of betaine has been associated with cardiovascular disease and pulmonary hypertension 81,82 . While there are very few side effects recorded for betaine, 83,84 there is still not enough information on the long‐term effects of regular betaine supplementation.…”

Unveiling the metabolic landscape of pulmonary hypertension: insights from metabolomics

“…As is well known, betaine functions as a methyl donor in the methionine cycle. Betaine has been identified as a potential biomarker, and elevated plasma betaine levels are linked to PH severity [ 3 , 37 ]. However, betaine can improve PH by inhibiting SMC proliferation and exerting anti-inflammatory effects [ 38 , 39 ].…”