In the current study, we demonstrated a significant association between CAC progression and TyG index in a group with a low to borderline 10-years ASCVD risk. Even after adjusting for cardiovascular risk factors, there were an independent association and incremental prognostic value of TyG index with CAC progression. These results are consistent with previous studies which showed association between increased TyG index level and traditional CVD risk factors. [7,18-20]
Although the mechanism underlying the association between TyG and CAC is still unclear, the TyG index is a surrogate marker of IR, which may be important. In clinical practice, TG and glycemia are among the classic markers of cardiometabolic risk. Alteration in the levels of these markers is directly associated with IR, progression of atherosclerosis and genesis of CVD. IR is defined as a clinical or experimental condition in which glucose absorption and use are impaired. [21]. Previous studies have shown that IR induces an imbalance in glucose and lipid metabolism, which is associated with cardiovascular risk in various population groups. [21-23] HOMA-IR is a comparatively extensive method for IR assessment. [24] The TyG index is strongly correlated with HOMA-IR and hyperinsulinemia-normal blood glucose clamp (HIEC) and even outperforms HOMA-IR. [5,25].
In recent years, many clinical studies have shown that the TyG index correlates with the risk of developing cardiovascular disease. Sánchez Iñigo et al. and Li et al. showed that healthy participants with elevated TyG index are at higher risk of cardiovascular events in each retrospective cohort studies. [19,26] Thai et al. reported that elevated TyG index is correlated with the incidence and severity of coronary stenosis in patients with DM. [27] Park et al. reported that the TyG index is an independent predictor of the coronary artery calcification progression. [28] Liu et al also reported that the high TyG index increases the risk of asymptomatic myocardial damage. [29] Various studies have shown that patients with high TyG index are more likely to develop hypertension and diabetes, [20,30] which was also confirmed in the present research. In addition, several studies proposed that the TyG index can be also prognostic factor of major adverse cardiac events in patients with acute coronary syndrome and/or percutaneous coronary intervention (PCI) and DM. [31-33] Based on these studies, some suggested using the TyG index as an indicator for determining the secondary prevention policy. [34]
In several previous studies, it is well known that TyG index is a prognostic factor related to cardiovascular risk in several situations, but its meaning is relatively unknown in asymptomatic and low risk patients. The use of the CAC score in asymptomatic subjects at intermediate risk, as determined by traditional clinical stratification methods, such as the Framingham risk score, is considered appropriate/recommended with a class IIb level of evidence by 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease. The use of the CAC score is not indicated in high-risk patients, because aggressive preventive measures would already be indicated in such patients. Within the group of patients classified as being at low risk, we have attempted to identify a subgroup with a significant long-term risk of a cardiovascular event, for which preventive measures should be adopted. [13]
In this study, we demonstrate that baseline CACS is also a meaningful factor for CACS progression to predict cardiovascular events in the low to borderline risk group, and the TyG index is also an independent factor for CACS progression in this group. We also found that TyG index is an incremental value that predicts CACS progression in addition to the clinical factor and baseline CAC. Therefore, considering the rationale for the prospective factor of the cardiovascular disorder of TyG in several previous studies, it is expected that it will be beneficial to consider both CACS and TyG in addition to the existing well-known clinical factor when determining the use of statins for primary prevention in a group below borderline risk
Limitation
There are some limitations to the present study. The present study only included subjects who experienced at least two CAC scan examinations with available data on the TyG index and diabetic status from the KOICA registry. So, potential selection bias might be present. Second, this was a retrospective observational study, which may be affected by unidentified confounders such as effect of medication for hypertension diabetes, and hyperlipidemia. Third, we only evaluated the association between the baseline TyG index and CAC progression. Fourth, the homeostatic model assessment of IR was not analyzed because insulin levels were not measured in the KOICA registry. Finally, the present study included only the Korean population.