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.