In our cross-sectional study, we found a significant and positive effect of the TyG index with the incidence of myocardial ischemia in patients with minimal to moderate CAD. Consequently, this study revealed that a higher TyG index was correlated with 19–24% elevated risk of myocardial ischemia detected by CT-FFR in patients with minimal to moderate CAD. This suggested that the TyG index may be help for identify with high risk of myocardial ischemia and then guiding further examinations and treatments in patients with minimal to moderate CAD.
Historically, coronary CTA was widely used to diagnose CAD in patients with low to moderate cardiovascular risk and the vast majority of MI is caused by non-obstructive plaques 10. Furthermore, accumulated evidences of recent coronary CTA trials have reaffirmed that MI observed in follow-up of patients with non-obstructive CAD is as common as in patients with obstructive CAD 11,12. Moreover, recent studies have showed that approximately 50% to two-thirds of patients who underwent coronary CTA are detected with non-obstructive CAD 13,14. In addition, researches of the presence and stenosis degree, as well as the plaque location and plaque burden of coronary atherosclerotic in patients with non-obstructive CAD have been indicated of good association with prediction of future cardiovascular events 4,15–17. Other studies further increased the discrepancy of the results. Hadamitzky et al. reported a observational single-center study contains 1584 suspected CAD patients underwent coronary CTA during 5.6 years of follow-up and revealed that the non-obstructive CAD for predicting composite endpoint (all-cause death and non-fatal MI) was significant compared with no CAD (HR, 2.46; 95% CI: 1.02–5.90), while cardiac event (cardiac death and MI) was not (HR, 6.16; 95% CI: 0.80–47.3) 17. Maddox et al. further investigated a large cohort of 37, 674 patients with 1-year follow-up and found that 1-vessel or 2-vessel of non-obstructive CAD was not associated with mortality, while 3-vessel of non-obstructive CAD showed a significant association with mortality (HR, 1.6; 95% CI: 1.1–2.5) 16. These together indicated the clinical importance of non-obstructive CAD and most importantly need further risk stratification. CT-FFR has gained a reliable role in assessed lesion-specific ischemia beyond stenosis on coronary CTA for predicting clinical outcomes 18. Currently, a CT-FFR ≤ 0.80 was regarded as a positive result of myocardial ischemia and has been proved with valuable for guiding treatment and assessing prognosis. However, few studies focus on myocardial ischemia of non-obstructive CAD. A recent study reported that the current clinical management would have missed nearly 20% of non-obstructive CAD patients with myocardial ischemia 19. The current study showed that 16.9% (286/1697) of non-obstructive patients have myocardial ischemia according to the CT-FFR values, which was similar to previous study.
Accumulated studies have indicated that the TyG index paly a good role in identifying for high risk of atherosclerosis in asymptomatic. A retrospective registered study recruited 888 asymptomatic type 2 diabetes patients without CAD history and showed that the highest tertile of TyG index was significant correlated with high risk of coronary artery stenosis detected by coronary CTA after adjustment for clinical confounders (OR: 3.19; 95% CI, 1.371–7.424) 20. Moreover, consistent clinical studies have revealed that an elevated TyG index was associated with increased incidence of obstructive CAD in patients with type 2 diabetes, non-alcoholic fatty liver diseases, established CAD and hypertension 20–23. Nevertheless, compared to previous results, the current study focus on the functional significant stenosis of minimal to moderate CAD subjects detected by coronary CTA and CT-FFR and show that the highest tertie of TyG index is positive associated with an increased incidence of myocardial ischemia in patients with minimal to moderate CAD, which fills some gaps in the research field of the associations between the TyG index and CAD. In addition, subgroups analysis was further conducted to verify the universality of the conclusions and the results suggested that the higher TyG index can predict the occurrence of myocardial ischemia based on CT-FFR in patients with minimal to moderate CAD, irrespective of gender, hypertension, CT_LeSc and coronary stenosis. Thus, the conclusion in the present study has broad practicality in patients with minimal to moderate CAD.
The current study has some limitations. First, a causal relationship between the TyG index and myocardial ischemia risk could not be determined due to the observational nature of the current study. Thus, further prospective and multi-center studies are needed to confirm these findings. Although the study adjusted the potential clinical risk factors of myocardial ischemia and CAD, there are still some unmeasured or residual confounding existed in the present study. Second, as some treatments, such as antiplatelet, statins and anti-diabetic drugs are not fully considered, this may cause bias in the statistical results. Third, invasive FFR is still the golden standard for determining specific myocardial ischemia rather than CT-FFR although the perfect consistent between these two examinations have been proved. Last, the generalizability of our findings is limited with the single center enrollment.