Day‐to‐day fasting plasma glucose variability on the short‐term prognosis of ST‐segment elevation myocardial infarction: A retrospective cohort study

Abstract Background and Hypothesis Glycemic variability in one fact that explain the differences in cardiovascular outcomes. The short‐term fasting plasma glucose (FPG) variability may have an on major adverse cardiovascular events (MACE) in type 2 diabetes mellitus (T2DM) patients with ST‐segment elevation myocardial infarction (STEMI). Methods This study retrospectively analyzed T2DM patients who underwent emergent percutaneous coronary intervention (PCI) due to STEMI in Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, between January 2016 and March 2020. All patients underwent at least 5 FPG measurements during the perioperative period. FPG variability score (FPG‐VS) was defined as the percentage of the number of FPG variations > 1 mmol/L between two adjacent FPG measurements. The Cox proportional‐hazards model was used to estimate the relationship between FPG‐VS and MACE. A validation set was utilized to further evaluate the prognostic value of FPG‐VS in a standardized STEMI diabetic diet cohort following PCI intervention. Results A total of 612 patients were included in the retrospective cohort study. In comparison to the minimum quintile, FPG‐VS > 60% was associated with an increased risk of 30‐day MACE. Moreover, compared to FPG‐VS ≤ 20%, the FPG‐VS > 80% group had a higher risk of MACE (odd ratio [OR] = 4.87, 95% confidence interval [CI]: 2.55−5.28), recurrent angina pectoris (OR = 5.43, 95% CI: 2.27−8.27), nonfatal myocardial infarction (OR = 5.00, 95% CI: 2.47−7.69), heart failure (OR = 3.70, 95% CI: 1.92−5.54), malignant arrhythmia (OR = 4.63, 95% CI: 1.12−6.25) and cardiac death (OR = 1.41, 95% CI: 0.17−1.97). Consistent results were obtained after adjustment for HbA1c, demonstrating the robustness of FPGFPG‐VS. Moreover, the standard diet intervention group had a lower FPG‐VS index as well as a lower incidence of MACE. Conclusion Higher FPG variability is associated with an increased risk of MACE within 30 days in diabetes patients receiving PCI for STEMI. A standardized diet may improve the prognosis of STEMI patients by reducing the FPG‐VS.


| INTRODUCTION
Type 2 diabetes mellitus (T2DM) is a significant risk factor for cardiovascular disease (CVD), and glycemic control level has been shown to be positively associated with the risk of acute and chronic CVD complications in T2DM patients. A substantial body of evidence suggests that good glycemic control could significantly decrease the incidence of CVD complications in T2DM patients. 1,2 However, a report by the Action to Control Cardiovascular Risk in Diabetes trial revealed that glycemic control to near normalization could also increase the incidence of cardiovascular events. 3,4 Growing evidence suggests that lowering glycemic variability is an important factor influencing diabetes-related cardiovascular risk. 5,6 Glycemic variability is a component of glycemic control that can be detected using various methods. Indexes for evaluating glycemic variability during hospitalization, including the standard deviation (SD), mean (M) and coefficient of variation (CV) of fasting plasma glucose (FPG), were found to be independent predictors of cardiovascular risk in T2DM patients. 7,8 A prospective observational study at Ruijin Hospital in Shanghai found that the variability index independent of FPG mean (VIM) was an independent prognostic factor for adverse left ventricular remodeling in T2DM patients with ST-segment elevation myocardial infarction (STEMI). 9 Increasing evidence suggests that glycemic variability is an independent risk factor for diabetes complications, 5,10 since not only can it reflect the effect of glycemic control over the course of the disease, but also predict the risk of hyperglycemia or hypoglycemia. By definition, glycemic variability is quantified based on the glycemic measurements within 2 days or based on HbA1c, or over a longer period. 5,11 By reviewing the studies domestically and abroad, we found that the prognostic significance of FPG level during hospitalization, the glycemic level at admission, and maximum glycemic level during acute coronary syndrome, 12,13 as well as the significance of FPG-CV, FPG-SD, and VIM in the long-term prognosis of CVD, 9,10

| Data collection
Patient basic information included demographic data, medical history, history of diabetes medication, coronary artery angiography manifestation, and type of PCI intervention. MACE included recurrent angina pectoris (AP), nonfatal myocardial infarction (MI) (including PCI-related MI), malignant arrhythmia, heart failure (HF), and cardiac death. PCI-related MI was diagnosed using cTn increase >fivefold. Malignant arrhythmias included sinus arrest, type 2 second-degree atrioventricular (AV) block, third-degree AV block, > LOWN4 ventricular premature, ventricular tachycardia, and ventricular fibrillation.

| Ethical issues
The study conformed to the principles outlined in the Declaration of Helsinki, 17 (Figure 3).

| Testing set analysis
Consistent with the above findings, analysis of the testing cohort revealed a close association between hyperglycemia variability and the short-term prognosis of STEMI patients, indicating that FPG-VS is a robust indicator for evaluating glycemic variability.
Notably, the glycemic variability in the diet intervention group was lower, and the FPG-VS index was significantly lower compared to the control group (0.60 vs. 0.34, p < .0001), as shown in Supporting Information: Figure 6A. Additionally, it was accompanied by a shorter hospital stay (7.89 vs. 6.44, p < .001), as detailed in Supporting Information: Figure 6B/C. Furthermore, the incidence of MACE during hospitalization in the intervention group was significantly lower than in the control group (p < .001), as shown in Supporting Information: Figure 6D. risk of MACE. 10,18 On the other hand, good perioperative glycemic control (HbA1c ≤ 7.0%) is associated with a significant reduction in the incidence of in-stent restenosis. 9 In addition, several previous studies revealed that good glycemic control during the perioperative period in patients undergoing PCI is vital for preventing adverse cardiovascular events postoperatively. However, the effect of perioperative glycemic control remains controversial since the glycemic control in these studies was achieved based on the HbA1c level at a certain time point, without further considering glycemic variability. Indeed, glycemic variability has been reported to be effective in interpreting the incidence of adverse cardiovascular events. 6 In the present study, we proved that FPG-VS was an independent risk factor for CVD, consistent with the existing literature. 7,9,13,18 Most related studies focused on the long-term impact of glycemic variability on adverse cardiovascular events in diabetes patients, 7,9,14

| Limitation
Nevertheless, the findings of our study should be interpreted within the context of the following limitations: this was a single-center retrospective study that analyzed the significance of FPG-VS for short-term prognosis in diabetes patients receiving PCI. Therefore, more in-depth investigations are warranted to further validate our results.

| CONCLUSION
High levels of FPG-VS were independently associated with the increased risk of MACE in T2DM patients that underwent emergent PCI for STEMI.