Prognostic value of gut microbiota-derived metabolites in patients with ST-segment elevation myocardial infarction

Suhong Zhao; Yanan Tian; Shanjie Wang; Fan Yang; Junyan Xu; Zhifeng Qin; Xinxin Liu; Muhua Cao; Peng Zhao; Guohua Zhang; Zhuozhong Wang; Yiying Zhang; Yidan Wang; Kaiyang Lin; Shaohong Fang; Zhao Wang; Tianshu Han; Maoyi Tian; Huiyong Yin; Jinwei Tian; Bo Yu

doi:10.1016/j.ajcnut.2022.12.013

Prognostic value of gut microbiota-derived metabolites in patients with ST-segment elevation myocardial infarction

Am J Clin Nutr. 2023 Mar;117(3):499-508. doi: 10.1016/j.ajcnut.2022.12.013. Epub 2022 Dec 28.

Authors

Suhong Zhao¹, Yanan Tian², Shanjie Wang¹, Fan Yang¹, Junyan Xu³, Zhifeng Qin¹, Xinxin Liu¹, Muhua Cao¹, Peng Zhao¹, Guohua Zhang⁴, Zhuozhong Wang¹, Yiying Zhang⁵, Yidan Wang¹, Kaiyang Lin⁶, Shaohong Fang¹, Zhao Wang⁷, Tianshu Han⁸, Maoyi Tian⁹, Huiyong Yin¹⁰, Jinwei Tian¹¹, Bo Yu¹

Affiliations

¹ Department of Cardiology, Second Affiliated Hospital of Harbin Medical University, Harbin, China; Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China.
² Department of Cardiology, Second Affiliated Hospital of Harbin Medical University, Harbin, China; Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China; Department of Cardiology, The Affiliated Hospital of Chengde Medical College, Chengde, China.
³ Department of Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China; Ministry of Education, Key Laboratory of Hainan Trauma and Disaster Rescue, College of Emergency and Trauma, Hainan Medical University, Haikou, People's Republic of China.
⁴ Department of Cardiology, Harbin Second Hospital, Harbin, China.
⁵ Department of Epidemiology and Biostatistics, School of Public Health, Jiamusi University, Jiamusi, China.
⁶ Department of Cardiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, China.
⁷ School of Electronic Science and Engineering, University of Electronic Science and Technology of China, Chengdu, China.
⁸ Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, P. R. China.
⁹ School of Public Health, Harbin Medical University, Harbin, China; The George Institute for Global Health, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia.
¹⁰ CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health (SINH), University of the Chinese Academy of Sciences (UCAS), Chinese Academy of Sciences (CAS), Shanghai, China; School of Life Science and Technology, ShanghaiTech University, Shanghai, China; Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing, China.
¹¹ Department of Cardiology, Second Affiliated Hospital of Harbin Medical University, Harbin, China; Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China; Ministry of Education, Key Laboratory of Hainan Trauma and Disaster Rescue, College of Emergency and Trauma, Hainan Medical University, Haikou, People's Republic of China. Electronic address: tianjinweidr2009@163.com.

PMID: 36811471
DOI: 10.1016/j.ajcnut.2022.12.013

Abstract

Background: Studies about the prognostic role of gut microbiota-derived metabolites including phenylacetyl glutamine (PAGln), indoxyl sulfate (IS), lithocholic acid (LCA), deoxycholic acid (DCA), trimethylamine (TMA), trimethylamine N-oxide (TMAO), and its precursor trimethyllysine (TML) are limited in patients with ST-segment elevation myocardial infarction (STEMI).

Objectives: To examine the relationship between plasma metabolite levels and major adverse cardiovascular events (MACEs), including nonfatal MI, nonfatal stroke, all-cause mortality, and heart failure in patients with STEMI.

Methods: We enrolled 1004 patients with STEMI undergoing percutaneous coronary intervention (PCI). Plasma levels of these metabolites were determined by targeted liquid chromatography/mass spectrometry. The associations of metabolite levels with MACEs were assessed with the Cox regression model and quantile g-computation.

Results: During a median follow-up of 360 d, 102 patients experienced MACEs. Higher plasma PAGln (hazard ratio [HR], 3.17 [95% CI: 2.05, 4.89]; P < 0.001), IS (2.67 [1.68, 4.24], P < 0.001), DCA (2.36 [1.40, 4.00], P = 0.001), TML (2.66 [1.77,3.99], P < 0.001), and TMAO (2.61 [1.70, 4.00], P < 0.001) levels were significantly associated with MACEs independent of traditional risk factors. According to quantile g-computation, the joint effect of all these metabolites was 1.86 (95% CI: 1.46, 2.27). PAGln, IS and TML had the greatest proportional positive contributions to the mixture effect. Additionally, plasma PAGln and TML combined with coronary angiography scores including the Synergy between PCI with Taxus and cardiac surgery (SYNTAX) score (area under the curve [AUC]: 0.792 vs. 0.673), Gensini score (0.794 vs. 0.647) and Balloon pump-assisted Coronary Intervention Study (BCIS-1) jeopardy score (0.774 vs. 0.573) showed better prediction performance for MACEs.

Conclusions: Higher plasma PAGln, IS, DCA, TML, and TMAO levels are independently associated with MACEs suggesting that these metabolites may be useful markers for prognosis in patients with STEMI.

Keywords: Balloon pump-assisted Coronary Intervention Study jeopardy score; Gensini score; ST-segment elevation myocardial infarction; gut microbiota-derived metabolites; the Synergy between percutaneous coronary intervention with Taxus and cardiac surgery score.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Gastrointestinal Microbiome*
Humans
Percutaneous Coronary Intervention* / adverse effects
Percutaneous Coronary Intervention* / methods
Prognosis
ST Elevation Myocardial Infarction* / etiology
ST Elevation Myocardial Infarction* / surgery
Treatment Outcome

Substances

trimethyloxamine