This study demonstrated that subjects with higher GA levels had a significantly higher risk of developing DES-ISR than those with lower levels in ACS patients who underwent PCI. After adjustment for confounding factors, GA, either as a continuous or nominal variable, remained an independent risk factor for DES-ISR development. Moreover, adding serum GA value to the baseline risk model could enhance the ability of the baseline risk model to predict the occurrence of DES-ISR and improve the reclassification and discrimination ability. These findings provide new perspectives on applying GA in clinical practice, particularly about early risk stratification for DES-ISR in patients with ACS.
HbA1c is widely recognized as one of the recommended diagnostic criteria for diabetes. It reflects the glycaemic control status in 2–3 months. However, it does not reflect the state of blood glucose control perfectly, and it has the following limitation. Firstly, HbA1c was influenced by the lifespan of the erythrocyte. Therefore, it does not accurately reflect blood glucose status in patients with haemoglobin variants, iron deficiency and anaemia, G6-PD poverty, pregnancy, and advanced chronic kidney disease[21–23]. In contrast, serum GA levels are unaffected by red blood cell lifespan, making it more accurate than HbA1c. Secondly, GA includes multiple glycation sites, whereas, HbA1c has only one glycation site. It has been reported that the rate of glycosylation of GA is approximately 4.5 times faster than that of HbA1c, resulting in GA responding more rapidly than HbA1C when blood glucose changes. Finally, HBA1c only responds to long-term blood glucose control, while GA responds to short-term blood glucose and fluctuations in blood glucose[20, 25]. Accordingly, GA was superior to HbA1c in monitoring the effect before and after drug treatment.
In recent years, many studies have shown that elevated GA levels help identify populations susceptible to cardiovascular disease. The cross-sectional study from the Japanese people has reported that serum GA levels were prominently associated with the development of carotid artery intima-media thickness, which suggests the increased levels of serum GA can predict the progression of atherosclerosis[26, 27]. Meanwhile, several studies further demonstrate that higher serum GA levels are positively associated with CVD developmentand the severity of CAD[29, 30]. Furthermore, a series of evidence also confirmed that Increased GA levels were collected with heart failure, impaired coronary collateralization with CTO patients, and adverse coronary artery remodelling. In addition, serum GA levels were associated with a low response to clopidogrel and a collection with clinical prognosis in ACS patients. A study from Zhang et al.evaluated the prognostic value of GA in patients diagnosed with ACS who were treated with PCI showed that Elevated GA levels in the serum were associated with poor intermediate-term outcomes in low-risk ACS patients who underwent PCI, especially in patients with preexisting diabetes. Another observational study from Liu et al.followed up 2247 NSTE-ACS patients who were treated with PCI during 48 months and found that GA is highly correlated with cardio-cerebral events, including all-cause death, non-fatal myocardial infarction (MI), non-fatal ischemic stroke and ischemia-induced revascularization. Extending the above findings, Our result showed that GA is a positive association with DES-ISR in patients with ACS who underwent PCI. On account of our discovery, More effective management strategies to prevent the occurrence of ISR after coronary stenting is needed for these patients.
Subsequently, the reliability and stability of the study results were confirmed by multivariate and subgroup analysis, both of which indicated that GA was an independent risk factor for DES-ISR. Unexpectedly, the predictive value of GA was higher in the non-diabetic subgroup than in the diabetic subgroup, and there was an interaction between the two subgroups. The exact mechanism is unclear, but it may mean that in non-diabetic patients, elevated GA is closely related to the progression and occurrence of DES-ISR. This is consistent with previous studies suggesting that GA can be used as a predictor of cardiovascular events in non-diabetic patients. Moreover, The Atherosclerosis Risk in Communities Study showed that adding serum GA levels to models with known CVD risk factors can improve the prognostic ability for CVD. In accordance with the previous study, Our findings suggest that the prognostic of serum GA and risk of developing DES-ISR improved by the introduction of GA into the established baseline risk model, and its incremental predictive value for DES-ISR was moderate. This suggests that introducing GA into risk prediction models can better help us identify DES-ISR in clinical practice.
The potential mechanism inducing the association between elevated levels of serum GA with the development and progression of DES-ISR remains uncertain. However, it may be related to the following points: Firstly, High serum GA was associated with a low response to clopidogrel, which contribute to inadequate antiplatelet, promote platelet activation and aggregation, increases thrombosis. Furthermore, serum GA levels reflect glycemic variability, which leads to endothelial dysfunction, and numerous studies suggest that endothelial dysfunction play a crucial role in restenosis after coronary stent implantation[38, 39]. Finally, GA induces inflammatory mediators in vessel walls and promotes proliferation and migrations of VSMCs, which is a significant manifestation in the pathology of ISR.