Trimethylamine N-Oxide and Related Gut Microbe-Derived Metabolites and Incident Heart Failure Development in Community-Based Populations.

IF 7.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Circulation: Heart Failure Pub Date : 2024-08-01 Epub Date: 2024-08-09 DOI:10.1161/CIRCHEARTFAILURE.124.011569

W H Wilson Tang, Rozenn N Lemaitre, Paul N Jensen, Meng Wang, Zeneng Wang, Xinmin S Li, Ina Nemet, Yujin Lee, Heidi T M Lai, Marcia C de Oliveira Otto, Amanda M Fretts, Nona Sotoodehnia, Joseph A DiDonato, Fredrik Bäckhed, Bruce M Psaty, David S Siscovick, Matthew J Budoff, Dariush Mozaffarian, Stanley L Hazen

{"title":"Trimethylamine N-Oxide and Related Gut Microbe-Derived Metabolites and Incident Heart Failure Development in Community-Based Populations.","authors":"W H Wilson Tang, Rozenn N Lemaitre, Paul N Jensen, Meng Wang, Zeneng Wang, Xinmin S Li, Ina Nemet, Yujin Lee, Heidi T M Lai, Marcia C de Oliveira Otto, Amanda M Fretts, Nona Sotoodehnia, Joseph A DiDonato, Fredrik Bäckhed, Bruce M Psaty, David S Siscovick, Matthew J Budoff, Dariush Mozaffarian, Stanley L Hazen","doi":"10.1161/CIRCHEARTFAILURE.124.011569","DOIUrl":null,"url":null,"abstract":"Background: Growing evidence indicates that trimethylamine N-oxide, a gut microbial metabolite of dietary choline and carnitine, promotes both cardiovascular disease and chronic kidney disease risk. It remains unclear how circulating concentrations of trimethylamine N-oxide and its related dietary and gut microbe-derived metabolites (choline, betaine, carnitine, γ-butyrobetaine, and crotonobetaine) affect incident heart failure (HF).Methods: We evaluated 11 768 participants from the Cardiovascular Health Study and the Multi-Ethnic Study of Atherosclerosis with serial measures of metabolites. Cox proportional hazard models were used to examine the associations between metabolites and incident HF, adjusted for cardiovascular disease risk factors.Results: In all, 2102 cases of HF occurred over a median follow-up of 15.9 years. After adjusting for traditional risk factors, higher concentrations of trimethylamine N-oxide (hazard ratio, 1.15 [95% CI, 1.09-1.20]; P<0.001), choline (hazard ratio, 1.44 [95% CI, 1.26-1.64]; P<0.001), and crotonobetaine (hazard ratio, 1.24 [95% CI, 1.16-1.32]; P<0.001) were associated with increased risk for incident HF. After further adjustment for renal function (potential confounder or mediator), these associations did not reach Bonferroni-corrected statistical significance (P=0.01, 0.049, and 0.006, respectively). Betaine and carnitine were nominally associated with a higher incidence of HF (P<0.05). In exploratory analyses, results were similar for subtypes of HF based on left ventricular ejection fraction, and associations appeared generally stronger among Black and Hispanic/Latino versus White adults, although there were no interactions for any metabolites with race.Conclusions: In this pooled analysis of 2 well-phenotyped, diverse, community-based cohorts, circulating concentrations of gut microbe-derived metabolites such as trimethylamine N-oxide, choline, and crotonobetaine were independently associated with a higher risk of developing HF.Registration: URL: https://www.clinicaltrials.gov/; Unique identifiers: NCT00005133 and NCT00005487.","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e011569"},"PeriodicalIF":7.8000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335438/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Circulation: Heart Failure","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1161/CIRCHEARTFAILURE.124.011569","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/9 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Growing evidence indicates that trimethylamine N-oxide, a gut microbial metabolite of dietary choline and carnitine, promotes both cardiovascular disease and chronic kidney disease risk. It remains unclear how circulating concentrations of trimethylamine N-oxide and its related dietary and gut microbe-derived metabolites (choline, betaine, carnitine, γ-butyrobetaine, and crotonobetaine) affect incident heart failure (HF).

Methods: We evaluated 11 768 participants from the Cardiovascular Health Study and the Multi-Ethnic Study of Atherosclerosis with serial measures of metabolites. Cox proportional hazard models were used to examine the associations between metabolites and incident HF, adjusted for cardiovascular disease risk factors.

Results: In all, 2102 cases of HF occurred over a median follow-up of 15.9 years. After adjusting for traditional risk factors, higher concentrations of trimethylamine N-oxide (hazard ratio, 1.15 [95% CI, 1.09-1.20]; P<0.001), choline (hazard ratio, 1.44 [95% CI, 1.26-1.64]; P<0.001), and crotonobetaine (hazard ratio, 1.24 [95% CI, 1.16-1.32]; P<0.001) were associated with increased risk for incident HF. After further adjustment for renal function (potential confounder or mediator), these associations did not reach Bonferroni-corrected statistical significance (P=0.01, 0.049, and 0.006, respectively). Betaine and carnitine were nominally associated with a higher incidence of HF (P<0.05). In exploratory analyses, results were similar for subtypes of HF based on left ventricular ejection fraction, and associations appeared generally stronger among Black and Hispanic/Latino versus White adults, although there were no interactions for any metabolites with race.

Conclusions: In this pooled analysis of 2 well-phenotyped, diverse, community-based cohorts, circulating concentrations of gut microbe-derived metabolites such as trimethylamine N-oxide, choline, and crotonobetaine were independently associated with a higher risk of developing HF.

Registration: URL: https://www.clinicaltrials.gov/; Unique identifiers: NCT00005133 and NCT00005487.

查看原文本刊更多论文

社区人群中的三甲胺 N-氧化物和相关肠道微生物衍生代谢物与心力衰竭发病率。

背景：越来越多的证据表明，三甲胺 N-氧化物是膳食胆碱和肉碱的一种肠道微生物代谢产物，会增加心血管疾病和慢性肾脏疾病的风险。目前仍不清楚三甲胺 N-氧化物及其相关膳食和肠道微生物衍生代谢物（胆碱、甜菜碱、肉碱、γ-丁基甜菜碱和巴豆甜菜碱）的循环浓度如何影响心力衰竭（HF）的发病：我们对心血管健康研究和多种族动脉粥样硬化研究的 11 768 名参与者进行了评估，并对代谢物进行了连续测量。在对心血管疾病风险因素进行调整后，我们使用 Cox 比例危险模型来研究代谢物与高血压发病率之间的关系：在中位 15.9 年的随访期间，共有 2102 例心房颤动患者。调整传统风险因素后，三甲胺 N-氧化物浓度较高（危险比为 1.15 [95% CI，1.09-1.20]；PPPP 分别为 0.01、0.049 和 0.006）。甜菜碱和肉碱名义上与较高的房颤发病率有关（PConclusions：在这项对两个表型清晰、多样化、基于社区的队列进行的汇总分析中，肠道微生物衍生代谢物（如三甲胺 N-氧化物、胆碱和巴豆甜菜碱）的循环浓度与较高的心房颤动发病风险独立相关：URL：https://www.clinicaltrials.gov/；唯一标识符：NCT00005133和NCT00005487。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Circulation: Heart Failure 医学-心血管系统

CiteScore

12.90

自引率

3.10%

发文量

271

审稿时长

6-12 weeks

期刊介绍： Circulation: Heart Failure focuses on content related to heart failure, mechanical circulatory support, and heart transplant science and medicine. It considers studies conducted in humans or analyses of human data, as well as preclinical studies with direct clinical correlation or relevance. While primarily a clinical journal, it may publish novel basic and preclinical studies that significantly advance the field of heart failure.