Using a representative national sample of older adults in the United States, we found that a higher TYG index was independently associated with increased odds of SAAC, showing a nearly linear dose-dependent relationship, after adjusting for factors including demographics, cardiovascular risk factors, and multiple other potential covariates. Subgroup analysis showed that the direction of the relationship between the TYG index and the SAAC in different subgroups was consistent with the trend of the study population.
In recent years, the TYG index has been suggested as a surrogate marker of insulin resistance (IR) [15, 16]. IR, a state of reduced sensitivity and responsiveness to insulin action, has been identified as a hallmark of T2DM [17]. There is increasing evidence that IR and its related diseases are associated with the development of CVD in both diabetic and non-diabetic patients [18]. IR patients are known to be prone to multiple metabolic disorders, such as hyperglycemia, dyslipidemia, and hypertension, all of which are strongly associated with adverse CVD outcomes [19]. Therefore, IR is not only considered a pathogenic cause of cardiovascular disease but also a predictor of cardiovascular disease in the general population and in patients with diabetes. Therefore, it is particularly important to develop convenient and reliable screening tools to detect IR and predict cardiovascular risk. Previously, the homeostasis model assessment-estimated insulin resistance index (HOMA-IR) was a widely used measure of -cell function and IR, but it had limited utility in subjects on insulin therapy or without -cell function [20]. To address this limitation, the TYG index was developed, and the TYG index was used to evaluate insulin resistance. And it has been proven to be superior to HOMA-IR in evaluating IR in diabetic and non-diabetic patients. [21] Many diseases, including hypertension, myocardial infarction, peripheral artery disease, and COVID-19, have been shown to be excellent predictors of TYG [22–25].
Vascular calcification (VC) is defined as the deposition of minerals in the form of calcium phosphate complexes in the vasculature. Although VC is thought to be a normal part of the aging process, certain pathological processes, such as diabetes, hypertension, chronic kidney disease (CKD), and/or rare genetic diseases, may also play a role [26].VC and atherosclerotic vascular disease have an inseparable relationship [27]. In addition, arterial stiffness, which represents VC dysfunction, is known to be an independent predictor of cardiovascular mortality [28]. Elastin loss is accompanied by medial calcification, and elastin degradation is thought to further promote the osteogenic process in aortic tissue [29]. Over the years, studies have revealed various mechanisms of vascular calcification, such as induction of bone formation, apoptosis, altered Ca/P balance, and loss of inhibition. [30] From the above, we can infer that the underlying mechanism of the association between the TYG index and AAC may be related to IR, which involves functional and structural damage of the arterial wall, including impaired vasodilation caused by chemical mediators, reduced arterial wall distensibility (arterial stiffness), vascular calcification, and increased arterial wall thickness [31, 32]. Studies have shown that vascular disease associated with insulin resistance begins early in life. Children and adolescents with insulin resistance exhibit impairment of the arterial system compared to adolescents without insulin resistance, suggesting that insulin resistance plays a crucial role in the development of initial vascular damage [33, 34]. In adults with T2D pre-clinical onset, asymptomatic subjects are chronically characterized by insulin resistance. Latent vascular dysfunction begins to develop at this stage, so that patients with T2D are at increased cardiovascular risk before the disease is diagnosed [35].
Stratified analyses showed associations that were generally consistent with the main findings. However, we found that some subgroups, such as men, smokers, and patients with low BMI and CVD, had lower ORS than the corresponding subgroups but did not reach statistical significance. Male, smoking, hypertension, and diabetes are typical risk factors for CVD, and the presence of these factors may change and weaken the effect of IR on AAC [36]. In addition, only 70 SAAC participants were included in the subgroup of diabetic patients after stratification. As the reduction in sample size leads to potential bias, the results need to be validated in a larger population in the future. To our knowledge, this is the first study to examine the association between the TYG index and the SAAC in a large and representative national sample of older adults in the United States. Our study has the strengths of a rigorous protocol and quality control, a large representative sample, standardized measures of vascular calcification, and the integration of data on many important covariates from the NHANES studies. However, this study has several limitations. Firstly, as a cross-sectional observational study, a causal relationship between the TYG index and the SAAC cannot be determined. Secondly, the adjustment is partial, and residual confounders should always be ruled out. Finally, because all participants were US residents, generalization of the results to other populations with different demographics may be limited.