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.
1 Application
Application ID | Title |
51470 | Physical measurement, blood biochemistry, lifestyle, environmental exposure: causality, gene-environment interaction in relation to metabolic diseases and cancer risk. |
1 Return
Return ID | App ID | Description | Archive Date |
3794 | 51470 | 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 | 6 Sep 2021 |