Wallenberg Laboratory, Department of Molecular and Clinical Medicine and Sahlgrenska Center for Cardiovascular and Metabolic Research, University of Gothenburg, Gothenburg, Sweden; Sahlgrenska University Hospital, Department of Medicine, Gothenburg, Sweden.
Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland, Ohio, USA; Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, Ohio, USA.
JACC Heart Fail. 2023 Jul;11(7):810-821. doi: 10.1016/j.jchf.2023.03.008. Epub 2023 Apr 26.
Over the past years, it has become clear that the microbial ecosystem in the gut has a profound capacity to interact with the host through the production of a wide range of bioactive metabolites. The microbially produced metabolite imidazole propionate (ImP) is clinically and mechanistically linked with insulin resistance and type 2 diabetes, but it is unclear how ImP is associated with heart failure.
The authors aimed to explore whether ImP is associated with heart failure and mortality.
ImP serum measurements in 2 large and independent clinical cohorts of patients (European [n = 1,985] and North American [n = 2,155]) with a range of severity of cardiovascular disease including heart failure. Univariate and multivariate Cox regression analyses were performed to delineate the impact of ImP on 5-year mortality in the North American cohort, independent of other covariates.
ImP is independently associated with reduced ejection fraction and heart failure in both cohorts, even after adjusting for traditional risk factors. Elevated ImP was a significant independent predictor of 5-year mortality (for the highest quartile, adjusted HR: 1.85 [95% CI: 1.20-2.88]; P < 0.01).
The gut microbial metabolite ImP is increased in individuals with heart failure and is a predictor of overall survival.
在过去的几年中，人们已经清楚地认识到，肠道中的微生物生态系统通过产生广泛的生物活性代谢物，具有与宿主进行深刻相互作用的能力。微生物产生的代谢产物咪唑丙酸（ImP）与胰岛素抵抗和 2 型糖尿病在临床上和机制上有关联，但目前尚不清楚 ImP 与心力衰竭之间的关系。
作者旨在探讨 ImP 是否与心力衰竭和死亡率有关。
在包括心力衰竭在内的一系列心血管疾病严重程度的两个大型且独立的患者临床队列（欧洲队列 [n=1985] 和北美队列 [n=2155]）中测量血清中的 ImP 水平。进行单变量和多变量 Cox 回归分析，以描绘北美队列中 ImP 对 5 年死亡率的影响，且不受其他协变量的影响。
即使在调整了传统危险因素后，ImP 仍与两个队列中的射血分数降低和心力衰竭独立相关。升高的 ImP 是 5 年死亡率的显著独立预测因素（最高四分位数，调整后的 HR：1.85 [95%CI：1.20-2.88]；P<0.01）。
心力衰竭患者体内的肠道微生物代谢产物 ImP 增加，并且是总生存率的预测指标。
