Triglyceride-glucose index trajectory and arterial stiffness: results from Hanzhong Adolescent Hypertension Cohort Study

In the present study, we observed a significant association between the TyG index and baPWV as a measurement of arterial stiffness in the general population. In cross-sectional settings, the TyG index positively correlated with baPWV in both continuous variables and quartiles form. Furthermore, during a 12-year observation period, 3 heterogeneous patterns of TyG index trajectory were identified, with the high-increasing trajectory carrying the greatest odds of increased arterial stiffness. These findings suggest that high levels of insulin resistance, as well as long-term exposure to high insulin resistance, may play a role in the pathogenesis of arterial stiffness.

Triglyceride-glucose index trajectory and arterial stiffness: results from Hanzhong Adolescent Hypertension Cohort Study

TyG index is a surrogate marker of insulin resistance deemed to provide better predictive performance in cardiovascular disease. Mounting evidence from cohort studies has confirmed the elevated TyG index to be a reliable predictor of adverse cardiovascular events [10,11,12, 27,28,29,30]. As of late, the association between the TyG index and arterial stiffness has gained increasing attention. Lee et al. demonstrated that elevated TyG index independently associated with increased arterial stiffness as measured by baPWV in the Korean general population [13]. Likewise, Guo et al. reported the TyG index to be an independent risk factor for high baPWV among Chinese healthy individuals [15]. Emerging evidence also suggested that the TyG index was positively and independently associated with baPWV in older adults, diabetics, and hypertensive patients [14, 16, 31, 32]. Additionally, Wu et al. reported a longitudinal relationship between the baseline TyG index and arterial stiffness progression in the Kailuan cohort, indicating that a higher TyG index predicted a higher risk and faster progression of arterial stiffness [17]. Despite the abundance of evidence for a cross-sectional association between the TyG index and baPWV, our investigation has a few differences from previous studies. One of the most notable differences is the population composition. Our study consisted of participants from a population-based cohort, with diverse socio-economic characteristics [13, 15, 17]. Another difference is that the individuals included in this study were relatively young, with a mean age of 42 years. Middle adulthood (age 40 to 65 years) is the time where cardiovascular profile rapidly changes, and is also an important life stage for early detection and intervention of cardiovascular risk. With these points in mind, our study based on a general population suggests that the TyG index can also function as a useful early indicator of arterial stiffness and thus reflects cardiovascular risk in early middle age. Previous studies were mainly focused on the TyG index measured at a single time point, which may not capture long-term exposure. Considering the dynamic changes in TG, FBG, and therefore TyG index over time, the impact of longitudinal TyG index trends needs to be evaluated. In a recent study, Gao et al. observed 4 distinct trajectories of the TyG index over 20 years, each associated with a different risk of future peripheral artery disease, with the two-decade trajectory with an elevated TyG index presenting the greatest risk [33]. However, little is known about the longitudinal variation of the TyG index and its association with subsequent arterial stiffness. Consistent with previous studies, our findings confirmed a significant cross-sectional association of the TyG index with baPWV. Importantly, we expanded previous observations by identifying distinct TyG index trajectories from early to middle adulthood. To the best of our knowledge, this is the first report concerning the impact of long-term TyG index trajectory on the progression of arterial stiffness in the general population. We highlighted the fact that the TyG index could fluctuate over time, and a single time point measurement cannot fully reflect the heterogeneous patterns of trends. Long-term trajectories of the TyG index provide additional information about the cumulative burden of risk for arterial stiffness. Our findings further suggested that participants with consistently higher TyG index (mean TyG index > 8.8) from early to middle adulthood were more susceptible to increased arterial stiffness after adjustment for traditional risk factors. In clinical practice, such individuals require early and intensive screening and management of risk factors to prevent arterial stiffness and, consequently, cardiovascular events.

Although the underlying mechanisms accounting for the associations between the TyG index and arterial stiffness have not been fully elucidated, it appears to be related to insulin resistance. The insulin signaling pathway could be disturbed by insulin resistance, leading to oxidative stress and impaired endothelial function at the intima cells level, including endothelial cells, smooth muscle cells, and macrophages. Furthermore, insulin action could also be impaired by insulin resistance, promoting chronic low-grade inflammation and dysregulation of glucose homeostasis [34,35,36]. These processes contribute to the development of arterial stiffness. Our results also confirmed previous findings that participants with high TyG index quartiles showed higher hs-CRP levels, a sensitive marker of inflammation, suggesting inflammation may be involved in the interplay between insulin resistance and arterial stiffness [17]. In 2008, Simental-Mendía et al. firstly introduced the TyG index as a surrogate to identify insulin resistance in apparently healthy subjects [37]. Growing evidence suggests that the TyG index performs better for assessing insulin resistance and is better associated with CVD and arterial stiffness than the homeostasis model assessment for insulin resistance (HOMA-IR), which is a traditional and the most frequently used marker of insulin resistance [13, 31, 38,39,40,41]. The molecular mechanisms of the TyG index as an effective marker of insulin resistance have not been completely understood, but it may be related to impaired metabolic flexibility. Insulin resistance disrupts insulin-mediated suppression of glucose production, and perturbs fatty acid metabolism during accumulation of skeletal muscle triglyceride [42, 43]. Nevertheless, the underlying mechanisms still warrant further investigation at the pathway levels.

Our study also has several limitations that need to be acknowledged. First, the study population was restricted to northern Chinese individuals, limiting the generalizability of the findings. Second, the follow-ups were unequally spaced in time, resulting in a shortage of data from 2005 to 2013. Third, the sample of participants in the longitudinal analysis was relatively small, leading to the less precise estimation of the parameters, which was reflected as wide confidence intervals for ORs. And during the long-term follow-up, there is a loss of participants. However, baseline characteristics in 2005 were similar between the participants and non-participants, and the study cohort seems to be representative of the original study population (see Additional file 3: Table S3, Additional file 4: Table S4). Additionally, participants included in this study were relatively young, with the oldest being 45 years old at the latest follow-up, and the number of participants with high baPWV was rather small. Large-scale prospective population studies are required to further understand and confirm the conclusions. Despite these limitations, this is the first study to demonstrate the association between TyG index trajectories and arterial stiffness. The combination of cross-sectional and longitudinal analyses provides a comprehensive insight into this association.