Previous studies have confirmed a higher incidence of myocardial ischaemia and coronary microvascular dysfunction among patients with NAFLD by combining CT with CT-MPI or SPECT-MPI. The conclusion drawn was that NAFLD is an independent predictor of myocardial ischemia and coronary microvascular dysfunction[25, 26]. In our study, we combined SPECT-MPI with CT imaging to demonstrate for the first time that NAFLD is associated with MIS, rather than IF or PF, and that the L/S of NAFLD on CT was an independent predictor of MIS in patients experiencing primary STEMI. In addition, previous studies have indicated that the levels of sST2, which increase in the early stage of STEMI, inversely correlate with MIS[27]. Our results suggest that sST2 is associated with both STEMI and NAFLD. Furthermore, the expression of sST2 positively correlated with the L/S of NAFLD as observed on CT in patients with STEMI. This finding further confirmed the association between NAFLD detected on CT and MIS on SPECT-MPI in STEMI at the molecular level.
John et al. showed that IF and PF in patients with coronary heart disease may not correlate with the subsequent occurrence of AMI[28]. Conversely, Amir et al. revealed a correlation between PF and long-term cardiovascular events in healthy individuals[29]. Therefore, the impact of IF and PF on MIS among patients with STEMI still requires further investigation. Our results revealed no significant differences in the volume and FAI of the IF and PF between the groups with or without MIS. However, the L/S of NAFLD differed significantly. Regarding AMI, MIS correlated with coronary microvascular dysfunction and prompt reperfusion[30, 31]. Furthermore, NAFLD is an independent predictor of coronary microvascular dysfunction[26]. Therefore, we hypothesise that these findings may be attributed to coronary microvascular dysfunction, which is closely related to NAFLD and aggravates the MIS.
In comparison with one previous study[32], we observed that 19.7% (23 of 117) of patients with STEMI in our study had NAFLD. This variation may be attributed to our utilization of an L/S ratio < 1 to diagnose NAFLD instead of ultrasound. As widely acknowledged, NAFLD is associated with insulin resistance, obesity, dyslipidemia, and diabetes[33]. Our findings revealed elevated triglyceride levels in patients with STEMI and NAFLD. However, this coincides with traditional cardiovascular risk factors, thus failing to verify an association between NAFLD and STEMI. Research indicates that NAFLD can serve as a microvascular dysfunction predictor, which is more powerful than the burden of individual risk factors [26]. Our results suggest that the L/S ratio of NAFLD on CT is an independent predictor of MIS in patients with STEMI.
Through analysis of the NAFLD and FAMI GEO databases, we screened 20 DEGs shared by the two diseases. Following GO analysis, four DEGs were selected and confirmed in patients with FAMI using ELISA. The results indicated a significant decrease in sST2 levels among patients with FAMI in the NAFLD group than in those in the non-NAFLD group. Zhong et al. also identified DEGs associated with these two diseases through GEO database analysis[34]. However, compared to previous research, our study included a larger patient cohort in the database, with the AMI database being the first AMI patient group, potentially explaining the discrepancies observed in our findings.
The IL33/ST2L pathway has a protective effect on the myocardium, and sST2 can compete with ST2L to bind to IL33, thereby inhibiting this pathway[14]. The rapid increase in sST2 levels in the early stages of AMI predicts heart failure and mortality in patients with AMI[15, 16]. Our analysis revealed a reduction in sST2 levels among patients with STEMI with NAFLD than in those without NAFLD (P < 0.05), which suggests that NAFLD may contribute to decreased sST2 levels. Therefore, further investigation on the role of ST2 in NAFLD is warranted. Additionally, the expression of sST2 positively correlated with the L/S of NAFLD as observed on CT in patients with STEMI. The level of sST2, which was negatively correlated with MIS in [27]the early STEMI stage[27], was found to be reduced in the serum of STEMI patients with NAFLD, thus reinforcing the association between NAFLD and MIS at the molecular level. This indicates the need to prioritise this group when using sST2 levels to assess the prognosis of patients with STEMI and NAFLD. However, further investigation is needed to elucidate the underlying mechanism.
Our study has several limitations. Firstly, this was a single-centre retrospective study with a limited number of patients, which may have hampered the robustness of our findings. Additionally, it was unnecessary for patients who met the inclusion criteria to collect serum prospectively to verify the DEGs before receiving SPECT-MPI, resulting in a lack of SPECT-MPI data for these patients. Although an existing study supports our results, direct evidence is still lacking. Finally, the limitations associated with visual evaluation of perfusion and function are well known. However, for an experienced observer, the strong correlation observed between MIS calculated through visual segmental scoring and the reference assessment employing a circumferential profile and an objective threshold method supports the reliability of visual analysis[35].
In summary, our study is the first to demonstrate the association between NAFLD and MIS in patients with STEMI rather than IF or PF. The L/S ratio of NAFLD on CT may serve as an independent predictor of MIS in patients with STEMI. Moreover, the sST2 level, which negatively correlates with MIS in the early STEMI stage and positively correlates with the L/S of NAFLD on CT in patients with STEMI, thus reinforcing the association between NAFLD and MIS at the molecular level.