■越来越多的证据表明,三甲胺N-氧化物,膳食胆碱和肉碱的肠道微生物代谢产物,增加心血管疾病和慢性肾脏疾病的风险。目前尚不清楚三甲胺N-氧化物及其相关饮食和肠道微生物衍生代谢物的循环浓度(胆碱,甜菜碱,肉碱,γ-丁基甜菜碱,和巴豆甜菜碱)影响心力衰竭(HF)。
■我们对11768名来自心血管健康研究和动脉粥样硬化多种族研究的参与者进行了一系列代谢物测量。Cox比例风险模型用于检查代谢产物与突发HF之间的关联,调整心血管疾病危险因素。
■总之,2102例HF发生在15.9年的中位随访时间内。在对传统风险因素进行调整后,较高浓度的三甲胺N-氧化物(危险比,1.15[95%CI,1.09-1.20];P<0.001),胆碱(危害比,1.44[95%CI,1.26-1.64];P<0.001),和巴豆甜菜碱(危害比,1.24[95%CI,1.16-1.32];P<0.001)与HF事件风险增加相关。在进一步调整肾功能(潜在的混杂或介质)后,这些关联未达到Bonferroni校正的统计学意义(分别为P=0.01,0.049和0.006).甜菜碱和肉碱名义上与较高的HF发病率相关(P<0.05)。在探索性分析中,基于左心室射血分数的HF亚型的结果相似,黑人和西班牙裔/拉丁裔成年人与白人成年人之间的联系普遍更强,尽管没有任何代谢物与种族的相互作用。
■在对2种良好表型的汇总分析中,多样化,以社区为基础的队列,肠道微生物衍生的代谢物如三甲胺N-氧化物的循环浓度,胆碱,巴豆甜菜碱和巴豆甜菜碱与发生HF的较高风险独立相关。
■URL:https://www。clinicaltrials.gov/;唯一标识符:NCT00005133和NCT00005487。
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: URL: https://www.clinicaltrials.gov/; Unique identifiers: NCT00005133 and NCT00005487.