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. 2022 Nov 3;21(1):229.
doi: 10.1186/s12933-022-01658-7.

Triglyceride-glucose index and the risk of heart failure: Evidence from two large cohorts and a mendelian randomization analysis

Xintao Li #  1   2 , Jeffrey Shi Kai Chan #  2 , Bo Guan  3 , Shi Peng  1 , Xiaoyu Wu  1 , Xiaofeng Lu  1 , Jiandong Zhou  2   4 , Jeremy Man Ho Hui  2 , Yan Hiu Athena Lee  2 , Danish Iltaf Satti  2 , Shek Long Tsang  2 , Shouling Wu  5 , Songwen Chen  6 , Gary Tse  7   8   9 , Shaowen Liu  10
Affiliations

Triglyceride-glucose index and the risk of heart failure: Evidence from two large cohorts and a mendelian randomization analysis

Xintao Li et al. Cardiovasc Diabetol. .

Abstract

Background: The relationship between triglyceride-glucose (TyG) index, an emerging marker of insulin resistance, and the risk of incident heart failure (HF) was unclear. This study thus aimed to investigate this relationship.

Methods: Subjects without prevalent cardiovascular diseases from the prospective Kailuan cohort (recruited during 2006-2007) and a retrospective cohort of family medicine patients from Hong Kong (recruited during 2000-2003) were followed up until December 31st, 2019 for the outcome of incident HF. Separate adjusted hazard ratios (aHRs) summarizing the relationship between TyG index and HF risk in the two cohorts were combined using a random-effect meta-analysis. Additionally, a two-sample Mendelian randomization (MR) of published genome-wide association study data was performed to assess the causality of observed associations.

Results: In total, 95,996 and 19,345 subjects from the Kailuan and Hong Kong cohorts were analyzed, respectively, with 2,726 cases of incident HF in the former and 1,709 in the latter. Subjects in the highest quartile of TyG index had the highest risk of incident HF in both cohorts (Kailuan: aHR 1.23 (95% confidence interval: 1.09-1.39), PTrend <0.001; Hong Kong: aHR 1.21 (1.04-1.40), PTrend =0.007; both compared with the lowest quartile). Meta-analysis showed similar results (highest versus lowest quartile: HR 1.22 (1.11-1.34), P < 0.001). Findings from MR analysis, which included 47,309 cases and 930,014 controls, supported a causal relationship between higher TyG index and increased risk of HF (odds ratio 1.27 (1.15-1.40), P < 0.001).

Conclusion: A higher TyG index is an independent and causal risk factor for incident HF in the general population.

Clinical trial registration: URL: https://www.chictr.org.cn ; Unique identifier: ChiCTR-TNRC-11,001,489.

Keywords: Heart failure; Insulin resistance; Mendelian randomization; Risk stratification; Triglyceride-glucose index.

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Conflict of interest statement

These authors declare that they have no conflicts of interests.

Figures

Fig. 1
Fig. 1
Kaplan-Meier curve of the cumulative incidence of incident heart failure stratifying by quartiles of the triglyceride-glucose index. (A) Kailuan cohort and (B) Hong Kong cohort
Fig. 2
Fig. 2
Subgroup analysis of the association between TyG index and incident HF for the (A) Kailuan cohort and (B) Hong Kong cohort Abbreviations: TyG: triglyceride-glucose; HR: hazard ratio; CI: confidence interval
Fig. 3
Fig. 3
Forest plots for the meta-analysis of the association between TyG index with HF risk. (A) TyG index analyzed as a categorical variable. (B) TyG index analyzed as a continuous variable
Fig. 4
Fig. 4
Mendelian randomization (MR) association between genetically determined TyG index and HF. Sensitivity analysis 1: MR analysis through IVW method in SNPs pruned by linkage disequilibrium with R2 < 0.001 Sensitivity analysis 2: Multivariable MR through IVW method after adjusting for cofounders including BMI, SBP, DBP, LDL-c, HDL-c, and DM. Sensitivity analysis 3: MR analysis through IVW method after excluding any SNPs significantly associated with those confounders, including BMI, SBP, DBP, LDL-c, HDL-c, and DM. Abbreviations: SNPs: single-nucleotide polymorphisms; OR: odds ratio; IVW: inverse-variance weighted
See this image and copyright information in PMC

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