Higher circulating Trimethylamine N-oxide levels are associated with worse severity and prognosis in pulmonary hypertension: a cohort study

Yang, Yicheng; Yang, Beilan; Li, Xin; Xue, Lin; Liu, Bingyang; Liang, Yanru; Zhao, Zhihui; Luo, Qin; Liu, Zhihong; Zeng, Qingpeng; Xiong, Chang-ming

doi:10.1186/s12931-022-02282-5

Cited by 11 publications

(12 citation statements)

References 36 publications

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“…The increase in TMAO levels may be responsible for the detrimental effects thought to originate directly from choline [ 29 , 30 ]. We have demonstrated that TMAO levels are associated with poor prognoses in patients with PH [ 9 ] and that pulmonary vascular remodelling in monocrotaline-induced PH rats was ameliorated after TMAO decreased, followed by the regulation of proliferation, apoptosis, and vasodilator pathways [ 8 ]. Additionally, TMAO has been reported to aggregate PH by inducing macrophage/monocyte chemokines and cytokine production [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

“…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 ].…”

Section: Introductionmentioning

confidence: 99%

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

Yang,

Liu

et al. 2023

BMC Pulm Med

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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 50th 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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Yang,

Liu

et al. 2023

BMC Pulm Med

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“…Hence, TMAO inhibition can enhance cardiovascular disease prognosis ( 26 – 28 ). Notably, TMAO has become a prognostic indicator for various cardiovascular diseases, including atherosclerosis, heart failure, and pulmonary arterial hypertension ( 29 – 32 ). However, some studies have indicated that excessive SCFAs can induce Th1 and Th17 cell proliferation, which promotes inflammation ( 33 ), while some TMAO precursors have been found to exert protective effects on the cardiovascular system ( 34 ).…”

Section: Discussionmentioning

confidence: 99%

Gut microbiota and hypertension: a bibliometric analysis of recent research (2014–2023)

Jiao,

Li,

Zhang

et al. 2023

Front. Nutr.

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BackgroundCardiovascular diseases persist as the primary cause of mortality in the global population. Hypertension (HTN) is widely recognized as one of the most crucial risk factors contributing to severe cardiovascular conditions. In recent years, a growing body of research has highlighted the therapeutic potential of gut microbiota (GM) in addressing cardiovascular diseases, particularly HTN. Consequently, unraveling and synthesizing the connections between GM and HTN, key research domains, and the underlying interaction mechanisms have grown increasingly vital.MethodsWe retrieved articles related to GM and HTN from 2014 to 2023 using Web of Science. Bibliometric tools employed in this analysis include CiteSpace and VOSviewer.ResultFrom 2014 to 2023, we identified 1,730 related articles. These articles involved 88 countries (regions) and 9,573 authors. The articles were published in 593 journals, with 1000 references exhibiting co-occurrence more than 10 times. The number of studies in this field has been increasing, indicating that it remains a research hotspot. We expect this field to continue gaining attention in the future. China leads in the number of published articles, while the United States boasts the most extensive international collaborations, signifying its continued prominence as a research hub in this domain. Tain You-Lin, Hsu Chien-Ning, Raizada Mohan K, and Yang Tao are among the authors with the highest publication volume. Publications in this field are frequently found in nutrition, cardiovascular, and molecular biology journals. The most frequently occurring keywords include metabolic syndrome, cardiovascular disease, inflammation, short-chain fatty acids, trimethylamine N-oxide, chronic kidney disease, heart failure, and high-salt diet.ConclusionThe relationship between GM and HTN is presently one of the most active research areas. By employing bibliometric tools, we analyzed critical and innovative articles in this field to provide an objective summary of the primary research directions, such as the relationship between GM and HTN, GM metabolites, high-salt diet, the developmental origins of health and disease, obstructive sleep apnea-Induced hypertension and antihypertensive peptide. Our analysis aims to offer researchers insights into hotspots and emerging trends in the field of GM and HTN for future research reference.

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“…The observed relative reductions in Faecalibacterium, Roseburia and Fusicatenibacter in CTEPH patients [34], also associated with reductions in endotoxin, were potential causes of increased gut inflammation and permeability [42,53,54]. Thus, metabolic endotoxaemia due to translocation of endotoxin induced by gut dysbiosis, which is already implicated in chronic low-grade inflammation in other cardiovascular diseases [39], may have a role in the pathogenesis of CTEPH.…”

Section: Lipopolysaccharidesmentioning

confidence: 98%

Pulmonary Hypertension and the Gut Microbiome

Mason,

Mukherjee,

Marino

2024

Biomedicines

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The gut microbiome and its associated metabolites are integral to the maintenance of gut integrity and function. There is increasing evidence that its alteration, referred to as dysbiosis, is involved in the development of a systemic conditions such as cardiovascular disease (e.g., systemic hypertension, atherosclerosis). Pulmonary hypertension (PH) is a condition characterised by progressive remodelling and vasoconstriction of the pulmonary circulation, ultimately leading to right ventricular failure and premature mortality if untreated. Initial studies have suggested a possible association between dysbiosis of the microbiome and the development of PH. The aim of this article is to review the current experimental and clinical data with respect to the potential interaction between the gut microbiome and the pathophysiology of pulmonary hypertension. It will also highlight possible new therapeutic targets that may provide future therapies.

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Higher circulating Trimethylamine N-oxide levels are associated with worse severity and prognosis in pulmonary hypertension: a cohort study

Cited by 11 publications

References 36 publications

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

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

Gut microbiota and hypertension: a bibliometric analysis of recent research (2014–2023)

Pulmonary Hypertension and the Gut Microbiome

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