The predictive value of eGDR for unfortunate prognosis in those with NSTE-ACS but no diabetes following PCI is being assessed for the first time in this study. Studies have shown an increment in the incidence frequency of MACCEs in those with low eGDR levels. The decline in eGDR is still a relevant independent forecaster of poor prognosis in the evaluated subjects even after adjusting confounding variables. The ability of baseline models comprising traditional risk factors to forecast the possibility of unfortunate prognosis was greatly enhanced by eGDR.
Defects in the insulin signaling pathway leading to impaired glucose metabolism in insulin-resistant individuals were strongly related to the atherosclerosis development, and compensatory hyperinsulinemia exacerbates the progression of AS through a variety of pathways when pancreatic β cells attempt to compensate for the defect in insulin action by increasing insulin secretion [25–28]. The development of atherosclerosis in non-diabetic patients was highly correlated with IR evaluated by the gold standard for diagnosing IR, the HIEG clamp [29, 30]. As evidenced from the aforementioned research, HIEG has only analyzed a relatively small number of patients on IR due to its inability to be extensively employed. Therefore, studies on the relationship between IR and CVD progression and prognosis mostly use HOMA-IR to evaluate IR.
The Botnia study showed that, following an average follow-up of 6.9 years, IR as weighed by HOMA-IR represented an independent forecaster of increased risk of CVD in non-diabetic patients [9]. Another study with an 8-year follow-up also confirmed the important predictive value of HOMA-IR for cardiovascular disease risk in non-diabetic patients [10]. HOMA-IR assessment of IR requires the detection of fasting insulin levels in patients. Even diabetic patients who were hospitalized for PCI in the cardiovascular department do not routinely have their fasting insulin levels checked in clinical practice. Moreover, the accuracy of insulin measurement methods is difficult to ensure consistently across laboratories, especially when insulin levels are low. However, several investigations have found a slight correlation between HOMA-IR and the level of IR in healthy individuals [31, 32]. As a result, clinical practice is more likely to adopt more operable alternative assessment indicators to assess each patient's level of IR in non-diabetic patients. Studies revealed that IR is frequently characterized by elevated fasting glucose, elevated TG, and obesity in addition to elevated fasting insulin levels (especially increased visceral fat) [33]. Based on these factors, a selection of less complex alternative indicators of IR have been proposed by researchers, such as TG/HDL-C, triglyceride-glucose (TyG) index, visceral adiposity index (VAI), etc., and have been confirmed to be significantly correlated with HIEG clamp [34–36]. Subsequent studies have established that the occurrence and progression of diabetes and cardiovascular disease are closely associated to these simple surrogate assessment indicators of IR [37–39]. In patients with pre-existing cardiovascular disease, these simple surrogate measures of IR have also proved their significant connection with unfortunate cardiovascular endings and the risk of recurrent major adverse cardiovascular events [40–43]. Studies have indicated that excessive TG/HDL-C levels and the TyG index are independently related to a greater risk of coronary heart disease in non-diabetic patients, while this correlation is not significant in diabetic patients [44].
When using as a simple surrogate for assessing IR, eGDR proved a significant correlation with an increased possibility of CVD in T1DM patients [45, 46]. Minor eGDR is associated with an increased possibility of stroke and death in T2DM patients, indicating that eGDR may behave as a predictive marker for these outcomes [47]. According to a countrywide observational research that included 3256 T2DM patients receiving CABG (median follow-up = 3.1 years), minor eGDR was tightly linked to an elevated possibility of death due to any reason and was not associated with other cardiovascular and metabolic risk variables [14]. Therefore, eGDR is speculated to have good performance in predicting long-standing poor forecast after PCI. Additionally, considering the application scenarios of eGDR as a simple surrogate for assessing IR, we attempted to conduct studies in non-diabetic populations.
Our study shows that low eGDR is a strong and stable predictor of poor prognosis after PCI in NSTE-ACS and non-diabetic populations. The findings in this study are consistent with previous related studies. Notably, in the subgroup analysis, eGDR presented greater predictive worth in the high BMI subcategory (BMI ≥ 28kg/m2) versus the low BMI subgroup (BMI < 28kg/m2). Earlier studies have shown that obesity can cause and exacerbate IR [48, 49]. At the same time, obesity is also a recognized traditional risk factor for CVD. We conjecture that elevated BMI enhances the predictive power of eGDR for long-term outcomes in the study population, but further research is needed to verify this. eGDR holds three elements: HbA1c, hypertension, and WC. As a recognized traditional risk factor for CVD, hypertension is the most essential constituent of eGDR [12]. In CVD patients with or without diabetes, HbA1c is thought as an independent forecaster of poor outcomes following PCI [50, 51]. Obesity is not only highly correlated with IR [33], but also with maladies such dyslipidemia, CVD, hypertension, and stroke [52]. In patients undergoing PCI, WC is connected with an augmented possibility of cardiac death and non-lethal MI [53].
There are several limitations to this study as well, which cannot be overlooked. Firstly, it should be considered that this is a single-center, observational study. Therefore, a larger-scale multi-center clinical trial involving more ethnic groups is needed to further validate the conclusions of this study. Secondly, this study did not perform a cross-sectional comparison of eGDR with other simple surrogate metrics for assessing IR. Therefore, future studies need to further clarify the role of eGDR as a predictor of CVD prognosis. Thirdly, since most of the NSTE-ACS patients in this investigation had UA, the predictive value of eGDR in NSTEMI patients may not be accurately reflected by these data.