In this study, we found positive association between TyG index and risk of peripheral arterial stiffness (cdPWV > 10.57 cm/s or crPWV > 11.12 cm/s). However, TyG index were not associated with central arterial stiffness, measured by cfPWV. Moreover, we found significant interactions between TyG index and BMI in relation to crPWV and cdPWV.
Several previous studies have shown that TyG index was associated with CVDs [19–20], and the detrimental effects of high TyG index might occur at early stage of AS [21–22]. In a recent cross-sectional study, it was found that TyG index was independently related to brachial ankle PWV (baPWV) in Korean subjects [23]. However, it is not clear whether TyG index specifically affect central or peripheral arterial stiffness because baPWV may be influenced by both sites [24]. Our results suggest that high TyG index are more likely to affect peripheral arterial stiffness, while its effect on central arterial stiffness is mild. Poon et al. [40] conducted a cross-sectional and cohort follow-up study on 2571 middle-aged and elderly people from the American community, and found that higher TyG index was associated with higher cfPWV in cross-sectional study. However, high aortic stiffness was not caused by faster annual rate of log-Homeostasis model of assessment-insulin resistance (HOMA-IR) or log-TyG in the follow-up study. The discrepancy between the results of their cross-sectional study and ours maybe caused by different study population, ethnic and sample size. In spite of this, our sample size is larger, and their long-term follow-up study verifies our study results. Therefore, the role of TyG index in aortic wall remodeling should be further studied in the future.
Several mechanisms may be underlying the associations of high TyG index and AS. Firstly, we suspect it may have something to do with IR. IR not only consists of a decrease in insulin's ability to process glucose, but also of impaired lipid oxidative utilization [25]. And the decrease of the secretion of insulin by beta cells inevitably leads to a decrease in the amount of functional insulin, which then could cause a decrease of the body's ability to process glucose and blood lipids [26]. The above two aspects will cause the body to show a state of hyperglycemia and hyperlipidemia [26]. The content of free fatty acids in the blood increases, enters non-adipose tissue and further synthesizes triglycerides and deposits, which could result in abnormal lipid metabolism and amplifies the basic metabolic disorders characterized by IR, leading to the occurrence of AS [27]. At present, TyG index is known as a surrogate marker of IR [28–30], and previous studies had proved that IR was closely related to PWV [9]. Therefore, we speculated that IR may play a crucial role in the occurrence of AS, which was mediated by TyG index. Secondly, most previous studies had suggested that AS was only associated with excessive lipid accumulation [27]. However, recent advances suggest that AS is a multifactorial and multigenic inflammatory condition in the arterial wall [31–32]. Some of the major risk factors for the development of AS, including hyperglycemia, dyslipidemia, and hyperinsulinemia, along with hypertension, smoking, and physical inactivity, are classified as metabolic syndrome, persistent presence of various atherogenic molecules instigates a hypoxic environment along with oxidative stress [33]. These changes could contribute towards enhanced ROS production in the cells, which activating and augmenting various inflammatory pathways, leading to the occurrence and development of AS [34]. Therefore, we speculated that TyG index may mediate the occurrence of AS through inflammation and oxidative stress.
The association between TyG index and AS under different BMI levels remained unclear. It is well known the association between BMI and AS [35]. Interestingly, our study found that there was an interaction between TyG index and BMI, which jointly affected AS. With the increase of BMI, the contribution of TyG index to the increase of crPWV and cdPWV decreased gradually. The adverse effect of TyG index on arterial stiffness was more obvious in people of normal weight than in obese population suggesting that TyG index could better reflect the risk of AS in people of normal weight. Further analysis showed that there was a dose-response relationship of TyG index with crPWV and cdPWV at different BMI levels, and the dose-response relationship was more obvious in individuals with BMI < 24 kg /m2. TyG index performed better in lean individuals probably because it was different from HOMA-IR, which mainly reflected muscle IR, while HOMA-IR reflected IR in the liver [25, 36]. A study about the association between TyG index and AS suggested that the TyG index may function in non-diabetic elderly populations through a different pathway from HOMA-IR [40]. Meanwhile, Lamb et al. [21] conducted a cross-sectional study of 473 postmenopausal women in Greek population, and found that TyG index was significantly better than metabolic syndrome in predicting subclinical AS in the population of postmenopausal lean women. More specifically, TyG index in lean postmenopausal women was significantly correlated with carotid intima media thickness, carotid atherosclerotic plaque formation, and aortic hardness as measured by PWV, which was similar to our findings.
To our knowledge, studies about the interactions of BMI and TyG index on AS in general population of Chinese adults are lacking. There are some limitations that should be considered in the cross-sectional study. First, causality between the TyG index and AS cannot be assured with certainty owing to the cross-sectional design. Second, our study was performed among Chinese adults, the result might not be applicable to other ethnicities. Third, the sample size was relatively small. In addition, the participants in our study were enrolled based on a community health examination survey, and thus the generalizability of the results may be limited. Further investigation on larger sample of subjects and longitudinal studies are needed to establish the causality between TyG index and AS.