We showed that the TyG index is independently related to aortic IMT, a marker of subclinical atherosclerosis in healthy individuals without any previous cardiovascular disease or diabetes. Several investigations have linked the TyG index to ASCVD risk factors such as type 2 diabetes [8, 18], hypertension [19], and metabolic syndrome [20]. Other CVD surrogate measures related to the TyG index include coronary artery calcium score [21], IMT of carotid arteries, and arterial stiffness [22, 23]. A few studies have found a link between the TyG index and CVD in high-risk patients with diabetes and chronic renal disease [24-26]. To our knowledge, our study is the first to show an independent relationship between the TyG index and the thoracic aorta IMT. The Triglyceride-glucose index is directly proportional to the blood glucose and triglyceride levels, and both levels appear to be increased in individuals with insulin resistance. The causal relationship between insulin resistance and atherosclerosis is well established in the literature.
Examining the association between blood glucose and triglyceride levels separately with atherosclerosis can reveal the relationship between the TyG index and atherosclerosis. At the beginning of insulin resistance, increased lipolysis of stored triglycerides in adipose tissue and increased production of fatty acids in the liver increase triglyceride levels before elevating plasma glucose levels. Therefore, at the beginning of insulin resistance, fasting glucose remains in the normoglycemic range [27]. Several meta-analyses with many patients have shown that fasting plasma glucose levels, already within the normoglycemic range (<100 mg/dL), are associated with the risk of developing coronary heart disease in subjects without diabetes mellitus. The risk of coronary disease increased linearly with blood glucose levels, independent of other established CVD risk factors, and the increased risk of diabetes [28] did not mediate it. Fasting glucose concentration is associated with coronary artery risk in people without diabetes, with an increased risk of 6% for every 1 mmol/L increment (18 mg/dL) in fasting plasma glucose, according to a meta-analysis of 26 prospective studies involving over 300,000 people [29].
Another finding in insulin resistance is elevated triglyceride levels, whose relationship with cardiovascular risk and mortality is disputed [30]. The difficulty in isolating hypertriglyceridemia's effect on cardiovascular disease is that it is frequently associated with other atherogenic lipid diseases, such as decreased HDL cholesterol and higher LDL cholesterol levels. In our study, we entered all lipid parameters in multivariate analysis to isolate the effect of triglycerides on IMT. However, in some studies, the relationship between triglyceride levels and cardiovascular disease became nonsignificant after adjusting for other lipid disorders and major variables; most studies found a direct association of triglyceride levels with increased risk and worse outcomes. Elevation of plasma free fatty acids activates the proinflammatory NFκB pathway [31], resulting in increased hepatic expression of several proinflammatory cytokines, including TNF-α, IL1-β, IL6, matrix metalloproteinases [32]; these inflammatory changes which play a significant role in the development of atherosclerosis [33]. It has been shown that daily administration of 2 g of icosapent ethyl reduces the frequency of cardiovascular death and ischemic events in patients who have recently used statins for coronary artery disease and still have high triglyceride levels (135-499 mg/dl).
Since plaque thickness rather than morphology is thought to be a more objective and reliable indicator of atherosclerotic disease, most grading systems use the maximum plaque thickness of the most diseased segment. However, there are a few grading systems of aortic atheroma based on IMT; no standard or widely accepted IMT cut-off is available for classification [17]. We used the median value of 1.42 mm as a cut-off to indicate high IMT. In literature, IMT higher than 1.5 mm was associated with an increased risk of coronary artery disease and stroke [34]. Although our definition of having a high IMT may seem arbitrary, the median IMT value of the patients in our study is very close to the value known to increase the risk of coronary artery disease and stroke (1.42 vs. 1.5), provides a rational basis for our definition. Since atherosclerosis begins in the thoracic aorta earlier than in the carotid arteries [4, 35], our study has the advantage of delineating the relationship between TyG and subclinical atherosclerosis better than studies performed on the carotid arteries.
Lifestyle modifications or drug therapies are recommended for primary prevention by calculating the fatal and non-fatal cardiovascular disease risk using scoring systems (SCORE2 and SCORE2-OP) based on age, sex, blood pressure, smoking status, and non-HDL cholesterol levels [3]. In addition, some non-invasive tests like coronary artery calcium score [36, 37] and carotid ultrasound helps to reclassify individuals to a higher or lower risk category. Based on our findings, we may suggest that the TyG index can also be used for adding information on the calculated SCORE risk
Most of the subjects included in our study are young individuals (mean age 40.38 ± 15.29 years) with low cardiovascular risk. They represent a narrow area of the cardiovascular risk spectrum compared to the general population. In addition, the cross-sectional structure of our study makes it difficult to reveal the cause-effect relationship. These are major limitations of our study.