Abstract
Background
This study aimed to investigate the associations between the triglyceride-glucose (TyG) index in young adulthood with incident cardiovascular disease (CVD) and mortality.
Methods
We included 4,754 participants from the Coronary Artery Risk Development in Young Adults study at baseline. The TyG index was calculated as ln (fasting TG [mg/dl] × fasting glucose [mg/dl]/2), and the TyG index trajectories were identified by using the latent class growth mixture model. We evaluated the association between the baseline and trajectories of the TyG index with incident CVD events and all-cause mortality using Cox proportional hazards regression analysis. The added value of the TyG index included in pooled cohort equations for CVD prediction was also analyzed.
Results
Among 4754 participants (mean age 24.72 years, 45.8% male, 51.2% black), there were 158 incident CVD events and 246 all-cause mortality during a median 25 years follow-up. After adjusting for multiple confounding variables, each one-unit increase in the TyG index was associated with a 96% higher CVD risk (hazard ratio [HR] 1.96, 95% confidence interval [CI] 1.44–2.66) and a 85% higher all-cause mortality risk (HR 1.85, 95% CI 1.45–2.36). Three distinct trajectories of the TyG index along the follow-up duration were identified: low (44.0%), moderate (45.5%), and high (10.5%). Compared with those participants in the low TyG index trajectory group, those in the high TyG index trajectory group had a greater risk of CVD events (HR 2.35, 95% CI 1.34–4.12) and all-cause mortality (HR 3.04, 95% CI 1.83–5.07). The addition of baseline TyG index to pooled cohort equations for CVD improved the C-statistics (P < 0.001), integrated discrimination improvement value (P < 0.001), and category-free net reclassification improvement value (P = 0.003).
Conclusions
Higher baseline TyG index levels and higher long-term trajectory of TyG index during young adulthood were significantly associated with an increased risk of incident CVD events and all-cause mortality in later life.
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Introduction
Cardiovascular disease (CVD) is the leading cause of global mortality and a major contributor to disability [1]. Over the past several decades, the incidence of CVD events has increased rapidly around the world [1] and tends to increase among younger individuals [2]. Therefore, early identifying those individuals at high risk of CVD and making effective preventive strategies for CVD starting at a young age is critically important. Insulin resistance is defined as a decrease in tissue response normally to insulin stimulation, which has been known to be one of the most critical risk factors for CVD [3, 4]. Recently, the triglyceride-glucose (TyG) index, measured by the fasting plasma glucose and triglyceride, has been proposed as a reliable surrogate marker of IR and shown to highly correlate with IR [5, 6]. Growing evidence has been demonstrated that the TyG index is related to adverse cardiovascular outcomes in the general population [7,8,9], as well as among certain high-risk patients, such as diabetes [26], their results showed no association between the TyG index and mortality or all-cause mortality. In fact, among the four studies they included, two found a statistically significant association between the TyG index and all-cause mortality [30, 31], while the other two did not [28, 32]. In studies of different populations, most articles found a positive association between the TyG index and cardiovascular mortality/all-cause mortality [14, 33, 34]. Another recent study of the Kangbuk Samsung Health Study cohort [35], including 255,508 relatively healthy populations, supported that the TyG index is associated with an elevated risk of all-cause and cardiovascular mortality. Overall, in this present study, among the general population of young adults, the TyG index is significantly associated with a high risk of all-cause mortality, and the long-term TyG index trajectory analysis also obtained consistent results.
The potential mechanism underlying the association of IR assessed by the TyG index with incident CVD events and mortality is still uncertain; several speculations have been summarized as follows. Firstly, as a reliable surrogate index for IR, the TyG index is well reflected and closely related to IR, which can induce an imbalance in glucose and lipid metabolism, leading to chronic hyperglycemia and dyslipidemia. These metabolic changes have been reported as the causes of cardiovascular disease and all-cause mortality by epidemiological or genetic evidence [36, 37]. In addition, there is a close relationship between the TyG index and traditional risk factors for cardiovascular diseases such as obesity [38], diabetes [39], hypertension [40], and renal insufficiency [38, 47]. Therefore, preservation of an appropriate level of TG and FBG within the desirable range and taking better control of long-term TyG index into late adolescence or young adulthood are critically important for reducing adverse health outcomes in the future.
The key strengths of the current study include the use of its community-based prospective cohort design, a high proportion of Black participants, and a long follow-up of a unique age group. However, there are also several limitations in this study. First, due to the young baseline age of the population, this study has only captured the premature events in later life thus far. Second, only biracial black and white population were included in this study; results may differ in other ethnicities of this age range. Third, given the observational study design of the CARDIA study, the causal relationship between TyG index with CVD events and mortality could not be fully evaluated. Fourth, although multivariable has been adjusted in the Cox regression model, residual confounders were still possible, including the medical therapy throughout the follow-up, environmental and behavioral factors, etc. Fifth, the hyperinsulinemic-euglycemic clamp test was unavailable in this study, so we cannot assess the correlation between the TyG index with the gold standard of IR by the hyperinsulinemic-euglycemic clamp test.
Conclusion
In summary, the current study shows that elevated levels of baseline TyG index and higher long-term trajectory of TyG index during young adulthood is strongly associated with high risk of incident CVD events and mortality in mid-life, independent of other traditional cardiovascular risk factors. Moreover, adding the TyG index to the PCEs model has an incremental effect on the predicted value of the CVD event. These findings support the contribution of a higher TyG index to the development of CVD events and mortality and indicate the importance of maintaining an appropriate level of TG and FBG within the desirable range beginning in late adolescence or young adulthood.
Availability of data and materials
All CARDIA data are obtained from the CARDIA Coordinating Center (https://www.cardia.dopm.uab.edu/contact-cardia). Details of the National Heart, Lung, and Blood Institute policies governing the data and how to access these data are available at (https://www.cardia.dopm.uab.edu/study-information/nhlbi-data-repository-data).
Abbreviations
- CARDIA:
-
Coronary artery risk development in young adults
- TyG:
-
Triglyceride-glucose
- CVD:
-
Cardiovascular disease
- SBP:
-
Systolic blood pressure
- DBP:
-
Diastolic blood pressure
- BMI:
-
Body mass index
- WC:
-
Waist circumference
- TC:
-
Total cholesterol
- TG:
-
Triglyceride
- LDL-c:
-
Low-density lipoprotein cholesterol
- HDL-c:
-
High-density lipoprotein cholesterol
- FBG:
-
Fasting blood glucose
- PCEs:
-
Pooled cohort equations
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Acknowledgements
We thank the staffs and participants of the CARDIA study for their contributions.
Funding
This study was supported by the National Natural Science Foundation of China (81870195, 82070384 to X.Liao; 81900329 to Y.Guo), Guangdong Basic and Applied Basic Research Foundation (2019A1515011582, 2021A1515011668 to X.Liao; 2019A1515011098, 2022A1515010416 to Y.Guo; 2021A1515110266 to Z. **ong) and the China Postdoctoral Science special Foundation funded project (2021TQ0386, 2021M703738 to Z. **ong).
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LXX, ZXD and XXH contributed to the conception or design of the work. All authors were responsible for the acquisition, analysis and interpretation of data. XXH, HRH and LYF drafted the manuscript. Critical revision of the manuscript for important intellectual content were performed by all authors. All author agreed with the content of the article to be submitted. All authors read and approved the final manuscript.
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The study was approved by the institutional review boards at all field centers of CARDIA study, and informed consent was obtained from all participants.
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The consent to publish was obtained from all participants in this study.
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All the authors declared no conflicting interests with respect to the research, authorship, or publication of this article.
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Supplementary Information
Additional file 1: Figure S1.
Flow chart for selecting the Coronary Artery Risk Development in Young Adults study participants for analysis. Figure S2. Subgroup analysis of the association between the baseline TyG index and all-cause mortality. Figure S3. The receiver operating characteristic (ROC) curves and diagnostic characteristics of the TyG index as a marker to predict CVD events (A) and all-cause mortality (B) in the CARDIA study. Table S1. E-value for the association between baseline TyG index with cardiovascular diseases and all-cause mortality (and its upper limit of 95% CI) in fully adjusted Cox models in CARDIA study. Table S2. Group-based trajectory model fit summary (N=4,138). Table S3. TyG index at examination years by trajectory groups of TyG index.
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Xu, X., Huang, R., Lin, Y. et al. High triglyceride-glucose index in young adulthood is associated with incident cardiovascular disease and mortality in later life: insight from the CARDIA study. Cardiovasc Diabetol 21, 155 (2022). https://doi.org/10.1186/s12933-022-01593-7
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DOI: https://doi.org/10.1186/s12933-022-01593-7