Causal Effect of the Triglyceride-Glucose Index and the Joint Exposure of Higher Glucose and Triglyceride With Extensive Cardio-Cerebrovascular Metabolic Outcomes in the UK Biobank: A Mendelian Randomization Study

Shucheng Si; Jiqing Li; Yunxia Li; Wenchao Li; Xiaolu Chen; Tonghui Yuan; Congcong Liu; Hongkai Li; Lei Hou; Bojie Wang; Fuzhong Xue

doi:10.3389/fcvm.2020.583473

Causal Effect of the Triglyceride-Glucose Index and the Joint Exposure of Higher Glucose and Triglyceride With Extensive Cardio-Cerebrovascular Metabolic Outcomes in the UK Biobank: A Mendelian Randomization Study

Front Cardiovasc Med. 2021 Jan 22:7:583473. doi: 10.3389/fcvm.2020.583473. eCollection 2020.

Authors

Shucheng Si^{1

2

3}, Jiqing Li¹, Yunxia Li¹, Wenchao Li¹, Xiaolu Chen¹, Tonghui Yuan¹, Congcong Liu¹, Hongkai Li^{1

2

3}, Lei Hou¹, Bojie Wang¹, Fuzhong Xue^{1

2

3}

Affiliations

¹ Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China.
² Institute for Medical Dataology, Shandong University, Jinan, China.
³ National Institute of Health Data Science of China, Jinan, China.

Abstract

Background: The causal evidence of the triglyceride-glucose (TyG) index, as well as the joint exposure of higher glucose and triglyceride on the risk of cardio-cerebrovascular diseases (CVD), was lacking. Methods: A comprehensive factorial Mendelian randomization (MR) was performed in the UK Biobank cohort involving 273,368 individuals with European ancestry to assess and quantify these effects. The factorial MR, MR-PRESSO, MR-Egger, meta-regression, sensitivity analysis, positive control, and external verification were utilized. Outcomes include major outcomes [overall CVD, ischemic heart diseases (IHD), and cerebrovascular diseases (CED)] and minor outcomes [angina pectoris (AP), acute myocardial infarction (AMI), chronic IHD (CIHD), heart failure (HF), hemorrhagic stroke (HS), and ischemic stroke (IS)]. Results: The TyG index significantly increased the risk of overall CVD [OR (95% CI): 1.20 (1.14-1.25)], IHD [OR (95% CI): 1.22 (1.15-1.29)], CED [OR (95% CI): 1.14 (1.05-1.23)], AP [OR (95% CI): 1.29 (1.20-1.39)], AMI [OR (95% CI): 1.27 (1.16-1.39)], CIHD [OR (95% CI): 1.21 (1.13-1.29)], and IS [OR (95% CI): 1.22 (1.06-1.40)]. Joint exposure to genetically higher GLU and TG was significantly associated with a higher risk of overall CVD [OR (95% CI): 1.17 (1.12-1.23)] and IHD [OR (95% CI): 1.22 (1.16-1.29)], but not with CED. The effect of GLU and TG was independent of each other genetically and presented dose-response effects in bivariate meta-regression analysis. Conclusions: Lifelong genetic exposure to higher GLU and TG was jointly associated with higher cardiac metabolic risk while the TyG index additionally associated with several cerebrovascular diseases. The TyG index could serve as a more sensitive pre-diagnostic indicator for CVD while the joint GLU and TG could offer a quantitative risk for cardiac metabolic outcomes.

Keywords: cardio-cerebrovascular diseases; causal association; glucose; triglyceride; triglyceride-glucose index.