Abstract
Background
The triglyceride-glucose (TyG) index and triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, two simple surrogate indicators of insulin resistance, have been demonstrated to predict cardiovascular disease (CVD). However, very few studies have investigated their associations with CVD in European populations.
Methods
A total of 403,335 participants from the UK Biobank with data for TyG index and TG/HDL-C ratio and free from CVD at baseline were included. Cox models were applied to evaluate the association between TyG index and TG/HDL-C ratio and incident CVD. Mediation analyses were performed to evaluate the contribution of prevalent diabetes, hypertension, and dyslipidemia to observed associations.
Results
During a median follow-up of 8.1 years, 19,754 (4.9%) individuals developed CVD, including 16,404 (4.1%) cases of CHD and 3976 (1.0%) cases of stroke. The multivariable-adjusted hazard ratios of total CVD in higher quartiles versus the lowest quartiles were 1.05, 1.05, and 1.19, respectively, for TyG index, and 1.07, 1.13, and 1.29, respectively, for TG/HDL-C ratio. There were significant trends toward an increasing risk of CVD across the quartiles of TyG index and TG/HDL-C ratio. In mediation analyses, dyslipidemia, type 2 diabetes, and hypertension explained 45.8%, 27.0%, and 15.0% of TyG index’s association with CVD, respectively, and 40.0%, 11.8%, and 13.3% of TG/HDL-C ratio’s association with CVD, respectively.
Conclusions
Elevated baseline TyG index and TG/HDL-C ratio were associated with a higher risk of CVD after adjustment for the well-established CVD risk factors. These associations were largely mediated by greater prevalence of dyslipidemia, type 2 diabetes, and hypertension.
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Introduction
Cardiovascular disease (CVD), including ischemic heart disease and stroke, constitute the leading cause of premature death worldwide [1]. In 2017, CVD caused an estimated 17.8 million deaths and was responsible for 330 million years of life lost globally [1]. This highlights the importance of identifying risk factors that could predict the risk of CVD and thereby facilitate its prevention at an early stage.
Insulin resistance, a pathophysiological condition characterized by the decreased insulin sensitivity of peripheral tissues, plays a key role in the development of metabolic syndrome and atherosclerosis [2, 3]. The euglycemic-hyperinsulinemic clamp is served as the gold standard to identify insulin resistance, but the technique is laborious, costly, and therefore impractical in the clinical setting [4]. The triglyceride-glucose (TyG) index and triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio have been proposed as simple and credible surrogate indicators of insulin resistance because they show strong correlations with the euglycemic-hyperinsulinemic clamp and they are suitable for clinical practice and large epidemiological studies [5, 6]. Several cross-sectional and retrospective studies have reported significant associations of the TyG index and TG/HDL-C ratio with incident CVD [14]. Furthermore, another 8-year prospective study of 796 participants showed that an elevated TG/HDL-C ratio predicted the incident risk of CVD events [21]. Consistent with prior studies, our study of a larger sample size confirmed that higher TyG index and TG/HDL-C ratio were significantly associated with increased risks of total CVD and CHD in the UK Biobank population. Neither the TyG index nor TG/HDL-C ratio was associated with stroke in our population after full covariate adjustment, in contrast with some earlier studies [39].
In conclusion, our analysis of data from the UK Biobank showed that elevated baseline TyG index and TG/HDL-C ratio, two surrogate markers of insulin resistance, were associated with a higher risk of CVD after adjustment for the well-established CVD risk factors. These associations were largely mediated by the greater prevalence of dyslipidemia, diabetes, and hypertension.
Availability of data and materials
The dataset supporting the conclusions of this article is available in the public UK Biobank Resource (www.ukbiobank.ac.uk/).
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Acknowledgements
We thank UK Biobank participants. This research has been conducted using the UK Biobank Resource (Application No 52632).
Funding
The study is supported by grants from by the National Natural Science Foundation of China (Grant 82173648), the Innovative Talent Support Plan of the Medical and Health Technology Project in Zhejiang province (2021422878), the Zhejiang Provincial Public Service and Application Research Foundation (LGF20H250001 and GC22H264267), Ningbo Health Branding Subject Fund (PPXK2018-01), the Internal Fund of Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences (2020YJY0212), Ningbo Clinical Research Center for Digestive System Tumors (2019A21003), Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo, China (2019E10020), the Public Welfare Foudation of Ningbo (2021S108), and Ningbo Science and Technology Innovation 2025 Specific Project (2020Z096).
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Conceptualization: BC and LH; Methodology: BC and CZ; Formal analysis and investigation: BC and CZ; Writing—original draft preparation: BC; Writing—review and editing: LH and YZ; Funding acquisition: LH; Resources: RZ, LP, and TZ; Supervision: YZ and LH All authors contributed to subsequent revisions and approved the final version. All authors read and approved the final manuscript.
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UK Biobank was constructed under ethical approval obtained by the North West Multi-Centre Research Ethics Committee (REC reference: 11/NW/03820) and all participants provided written informed consent prior to participation. The current analyses were carried out under Application Number 52632.
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Supplementary Information
Additional file 1: Table S1.
Characteristics of the study population according to the TG/HDL-C ratio quartiles. TG/HDL-C, triglyceride to high-density lipoprotein cholesterol; eGFR, estimated glomerular filtration rate. aContinuous variables are expressed as mean (SD). Categorical variables are expressed as frequency (percentage). Table S2. Correlations of the TyG index and TG/HDL-C ratio with participant characteristicsa. TyG, triglyceride-glucose; TG/HDL-C, triglyceride to high-density lipoprotein cholesterol; eGFR, estimated glomerular filtration rate. aPoint-biserial correlation for dichotomized variables and Pearson’s correlation for continuous variables. Table S3. Characteristics and cardiovascular outcomes of the study population in England, Scotland, and Wales. TyG, triglyceride-glucose; TG/HDL-C, triglyceride to high-density lipoprotein cholesterol; eGFR, estimated glomerular filtration rate. aContinuous variables are expressed as mean (SD). Categorical variables are expressed as frequency (percentage). Table S4. Sensitivity analysis: Multivariable-adjusted hazard ratios of cardiovascular disease associated with the TyG index and TG/HDL-C ratio, additionally adjusted for prevalent dyslipidemia, type 2 diabetes, and hypertension. TyG, triglyceride-glucose; TG/HDL-C, triglyceride to high-density lipoprotein cholesterol; HR, hazard ratio. aHazard ratios were adjusted for the variables included in model 3 in Table 2 in addition to prevalent type 2 diabetes, hypertension, and dyslipidemia. Table S5. Sensitivity analysis: Associations of the TyG index and TG/HDL-C ratio with risk of cardiovascular disease, excluding 6080 incident cases with less than 3 years of follow-up (N = 397,255). TyG, triglyceride-glucose; TG/HDL-C, triglyceride to high-density lipoprotein cholesterol; HR, hazard ratio. Hazard ratios were adjusted for the same variables included in model 3 in Table 2. Appendix S1. ICD-10 codes used to ascertain comorbidities and cardiovascular outcomes.
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Che, B., Zhong, C., Zhang, R. et al. Triglyceride-glucose index and triglyceride to high-density lipoprotein cholesterol ratio as potential cardiovascular disease risk factors: an analysis of UK biobank data. Cardiovasc Diabetol 22, 34 (2023). https://doi.org/10.1186/s12933-023-01762-2
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DOI: https://doi.org/10.1186/s12933-023-01762-2