三甲胺氧化物及相关肠道微生物衍生代谢物与社区人群心力衰竭发病的关系。
Trimethylamine -Oxide and Related Gut Microbe-Derived Metabolites and Incident Heart Failure Development in Community-Based Populations.
机构信息
Department of Cardiovascular and Metabolic Sciences (W.H.W.T., Z.W., X.S.L., I.N., J.A.D.D., D.M., S.L.H.), Lerner Research Institute, Cleveland Clinic, OH.
Center for Microbiome and Human Health (W.H.W.T., Z.W., X.S.L., I.N., J.A.D.D., S.L.H.), Lerner Research Institute, Cleveland Clinic, OH.
出版信息
Circ Heart Fail. 2024 Aug;17(8):e011569. doi: 10.1161/CIRCHEARTFAILURE.124.011569. Epub 2024 Aug 9.
BACKGROUND
Growing evidence indicates that trimethylamine -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 -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 -oxide (hazard ratio, 1.15 [95% CI, 1.09-1.20]; <0.001), choline (hazard ratio, 1.44 [95% CI, 1.26-1.64]; <0.001), and crotonobetaine (hazard ratio, 1.24 [95% CI, 1.16-1.32]; <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 (=0.01, 0.049, and 0.006, respectively). Betaine and carnitine were nominally associated with a higher incidence of HF (<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 -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.
背景
越来越多的证据表明，三甲胺氧化物是膳食胆碱和肉碱的肠道微生物代谢产物，可促进心血管疾病和慢性肾病的风险。目前尚不清楚循环三甲胺氧化物及其相关饮食和肠道微生物衍生代谢物（胆碱、甜菜碱、肉碱、γ-丁酰甜菜碱和巴豆酰甜菜碱）的浓度如何影响心力衰竭（HF）的发生。
方法
我们评估了心血管健康研究和动脉粥样硬化多民族研究中 11768 名参与者的连续代谢物，使用 Cox 比例风险模型来检查代谢物与心力衰竭发生之间的关联，同时调整了心血管疾病风险因素。
结果
在中位随访 15.9 年期间，共发生 2102 例 HF。在调整传统危险因素后，三甲胺氧化物（危险比，1.15[95%置信区间，1.09-1.20]；<0.001）、胆碱（危险比，1.44[95%置信区间，1.26-1.64]；<0.001）和巴豆酰甜菜碱（危险比，1.24[95%置信区间，1.16-1.32]；<0.001）浓度升高与 HF 发生风险增加相关。在进一步调整肾功能（潜在的混杂因素或中介物）后，这些关联未达到 Bonferroni 校正的统计学意义（分别为=0.01、0.049 和 0.006）。甜菜碱和肉碱与 HF 发生率升高呈名义相关（<0.05）。在探索性分析中，基于左心室射血分数的心力衰竭亚组的结果相似，并且在黑人和西班牙裔/拉丁裔与白人成年人中，关联似乎更强，尽管任何代谢物与种族之间均无相互作用。
结论
在这项由两个表现良好、多样化的社区为基础的队列组成的汇总分析中，肠道微生物衍生代谢物（如三甲胺氧化物、胆碱和巴豆酰甜菜碱）的循环浓度与 HF 发展风险的升高独立相关。
注册
网址：https://www.clinicaltrials.gov/；唯一标识符：NCT00005133 和 NCT00005487。
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