Introduction

ST-elevation myocardial infarction (STEMI) as a serious type of coronary artery disease (CAD)and stands as a leading cause of mortality and disability. Although percutaneous coronary intervention (PCI) has emerged as a critical intervention for acute myocardial infarction (AMI). Nevertheless, more than 6% of Asian AMI patients still face major adverse cardiovascular events (MACEs) within two years post-PCI1. Studies indicated a close relationship between insulin resistance and the onset and progression of atherosclerotic plaque, substantiating insulin resistance as a significant risk factor for CAD2,3. Insulin resistance disrupts the glucose and lipid metabolism balance, where chronic hyperglycemia from glucose metabolism disorders triggers oxidative stress and inflammation, culminating in cellular damage. Dysregulated lipid metabolism results in abnormal lipid profiles, such as elevated plasma triglycerides, reduced high-density lipoprotein (HDL-C) levels, and the formation of small, dense low-density lipoprotein particles, fostering atherosclerotic plaques’ development2.

Glycosylated hemoglobin A1c (HbA1c) serves as a long-term marker of blood glucose control, minimally affected by acute stress or glucose management, and elevated HbA1c is associated with increased risk of cardiovascular disease4. Irrespective of diabetes status, HbA1c emerges as a pivotal predictor of coronary artery stenosis severity in AMI patient5. Apolipoprotein A1 (ApoA1), the primary apolipoprotein of HDL-C, exerts anti-atherosclerotic effects, with lowered ApoA1 concentrations associated with an escalated risk of atherosclerotic cardiovascular disease6. Glycosylated hemoglobin A1c/Apolipoprotein (A1HbA1c/ApoA-1), an indirect marker of insulin resistance, serves as an accessible atherosclerosis indicator. This ratio also exhibits promise as a cardiovascular risk assessor in acute coronary syndrome (ACS) patients, can independently predict the risk of MACEs in patients with acute ACS. Moreover, an elevated HbA1c/ApoA-1 ratio is associated with a higher risk of MACEs7,8.

Nonetheless, the full extent of HbA1c/ApoA-1’s role in STEMI patient prognosis post-PCI remains unclear. Thus, this study explores the correlation between HbA1c/ApoA-1 and short-term prognosis in STEMI patients following PCI. And to expound on the predictive potential of the HbA1c/ApoA1 ratio for short-term MACEs in STEMI patients post-PCI, offering valuable predictive capabilities for early MACEs identification and mitigation.

Results

Baseline characteristics of the two groups in the study cohort

The baseline characteristics of the two groups enrolled in current study were shown in Table 1. Of the 182 patients studied, there were 152 males and 30 females, with an average age of 60.1 ± 12.1 years. Patients in the MACEs group were older than those in the non-MACEs group. The MACEs group exhibited a higher prevalence of diabetes, Killip grades III to IV, multi-vessel coronary artery disease, left ventricular end-diastolic diameter, left ventricular end-systolic diameter (LVESD), amino terminal brain natriuretic peptide precursor(pro-BNP), γ-glutamyl transferase, fasting plasma glucose, HbA1c, and HbA1c/ApoA-1 compared to the non-MACEs group. Conversely, the MACEs group had lower admission left ventricular ejection fraction (LVEF), hemoglobin, hematocrit, and serum albumin levels than the non-MACEs group. Furthermore, a higher proportion of patients in the MACEs group were using β-blockers, angiotensin receptor-neprilysin inhibitor or renin-angiotensin system inhibitor (ARNI/RASi), and sodium-glucose transporter inhibitors (SGLT2) during hospitalization compared to the non-MACEs group (all P < 0.05, Table 1).

Table 1 Baseline characteristics of the two groups enrolled in current study.
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Univariate and multi-factor logistic regression analysis of maces influencing factors of STEMI patients after PCI

Variables with a significance level of P < 0.05 in Univariate logistic regression were incorporated into the multi-factor logistic regression analysis, The results revealed that HbA1c/ApoA-1 served as an independent risk factor for MACEs in STMEI patients post-PCI. Additionally, other independent predictors encompassed Killip grade III, multivessel coronary artery disease, decreased LVEF, increased of LVESD. The differences exhibited statistical significance (P < 0.05), as shown in Table 2.

Table 2 Multi-factor Logistic regression analysis of MACEs influencing factors of STEMI patients after PCI.
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Different models and subgroup analysis confirmed the HbA1c/ApoA-1 ratio as an independent risk factor for maces

Different models showed a significant correlation between HbA1c/ApoA-1 and MACEs following PCI in Table 3. Model 1 was a crude model without adjusting for confounding variables. Model 2 adjusted for age and gender. Model 3 adjustments covered gender, age, hypertension, diabetes, cerebral infarction, PCI history, smoking, alcohol consumption, statin usage, and cardiac function classification, confirming the HbA1c/ApoA-1 ratio as an independent predictive marker for MACEs in STEMI patients post-PCI (OR:1.40 ;95%CI :1.13–1.73; P = 0.002) (in Table 3). Subgroup analysis revealed no significant interactions concerning gender, diabetes, smoking history, alcohol usage, Killip grade III, multi-vessel disease, and other subgroup variables (P interaction > 0.05), solidified the study’s result reliability (in Table 4).

Table 3 Different models analyzed the HbA1c/ApoA-1 was a predictor for maces.
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Table 4 Subgroup analysis and interaction.
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The predictive value of HbA1c/ApoA-1 for maces

Receiver operating characteristic (ROC) curve analysis illustrated the robust predictive capacity of HbA1c/ApoA-1 for MACEs in STEMI patients post-PCI, with an area under curve (AUC) of 0.752 (95%CI: 0.68–0.86) and corresponding sensitivity and specificity values of 85.7% and 56.8%, respectively. HbA1c/ApoA-1 ratio remained a reliable predictor for MACEs occurrence in STMEI patients post-PCI. As shown in Table 5; Fig. 1.

Table 5 Results of ROC curve analysis.
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Fig. 1
figure 1

ROC curve of HbA1c/ApoA-1 predicting MACEs in STEMI patients after PCI.

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Nonlinear relationship between HbA1c/ApoA-1 and maces

Restricted cubic spline (RCS) curve analysis showed a statistically significant nonlinear association (P nonlinearity = 0.023) between HbA1c/ApoA-1 and the occurrence of MACEs. The inflection point of the RCS curve was identified at HbA1c/ApoA-1 = 6.5. Subsequently, the dataset was stratified based on this inflection point, leading to the conduct of distinct logistic regression analyses for each segment. The results indicated that for HbA1c/ApoA-1 < 6.5, (OR: 3.95; 95%CI: 1.56–9.99, P = 0.004), Conversely, for HbA1c/ApoA-1 ≥ 6.5, (OR: 1.47; 95%CI: 0.96–2.26, P = 0.075). as shown in Fig. 2.

Fig. 2
figure 2

Nonlinear relationship between HbA1c/ApoA-1 and MACEs in STEMI patients after PCI. HbA1c/ApoA-1; glycosylated hemoglobin A1c/apolipoprotein A1.

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Discussion

This study retrospectively examined the influence of HbA1c/ApoA1 on the occurrence of MACEs in STEMI patients following PCI. The results indicated that the level of HbA1c/ APOA-1 in patients with MACEs was higher than that in patients without MACES. Adjusted for gender, age, hypertension, diabetes, cerebral infarction, PCI history, smoking, and other factors, elevated HbA1c/ApoA-1 levels remained an independent risk factor for MACE occurrence in this patient cohort, demonstrating predictive capability. There is statistically significant nonlinear association between HbA1c/ApoA-1 and the occurrence of MACEs.

Primary PCI has been shown to be an effective reperfusion therapy for STEMI to restore coronary artery blood flow and has contributed to reducing mortality rates, Nevertheless, the long-term prognosis of STEMI patients post-PCI remains suboptimal. primarily due to cardiovascular events occurring predominantly within the initial month following PCI11. Our study demonstrated that HbA1c/ApoA-1 can serve as a predictive factor for MACEs in patients with STEMI following PCI. It can be used to early identification and mitigation of the occurrence of MACEs.

Dysregulated glucose and lipid metabolism alongside insulin resistance are prominent factors heightening atherosclerosis risks, and diabetes can lead to myocardial ischemia and even myocardial infarction, contributing to cardiac structural changes and heart failure development12. Research indicates that Elevated HbA1c levels are associated with heightened cardiovascular disease risks in diabetic individuals and even non-diabetic individuals, correlating with increased overall mortality and cardiovascular ailments13,14. Furthermore, in non-diabetic individuals, HbA1c levels are positively correlated with the extent of coronary artery stenosis in AMI patients15,16. Thus, irrespective of diabetes status, HbA1c is strongly linked to poor prognosis of patients5,17. Yi Lao et al. examined 173 postmenopausal patients with ACS and diabetes, elevated HbA1c levels are associated with a higher incidence of MACEs post-PCI18. Kang Yi et al. analyzed 461 ACS patients and observed a relationship between HbA1c levels and the occurrence of in-hospital MACEs in myocardial infarction patients19. The reasons may be as follows, that high blood sugar levels can negatively impact endothelial function by reducing nitric oxide release and increasing superoxide production in the blood vessel wall20. And can promote the proliferation and migration of vascular smooth muscle cells, ultimately leading to vascular neointimal proliferation and in-stent restenosis after stent implantation21,22,23,24. Additionally, hyperglycemia, reflecting impaired insulin secretion, can trigger lipolysis and elevate circulating free fatty acids. Excessive free fatty acids may increase myocardial oxygen consumption, exert toxic effects on the myocardium, and result in ventricular arrhythmias and reduced myocardial contractility 25,26,27.

Both ApoA-1 and HDL-C exhibit protective effects against atherosclerosis. HDL-C, serving as a carrier of plasma cholesterol, possesses inherent anti-atherosclerotic and anti-inflammatory properties, yet may become dysfunctional in the presence of systemic and vascular inflammation, thereby promoting proatherogenic and proinflammatory responses28,29. ApoA-1 is one of the earliest discovered apolipoproteins and primary protein constituent of HDL-C30,31. ApoA-1 plays a crucial role in regulating cholesterol transport and metabolism by facilitating intracellular cholesterol efflux and transferring cholesterol from peripheral tissues to the liver for eventual excretion into the intestine via bile. It exhibits anti-atherosclerosis and cardiovascular disease properties32,33. The promotion of HDL-C synthesis by ApoA-1 is inversely correlated with vascular atherosclerosis and stenosis, making it a significant factor in atherosclerosis resistance. Moreover, ApoA-1 exhibits anti-inflammatory, anti-apoptotic, anti-thrombotic, and cardioprotective properties, reducing the possibility of cardiovascular diseases, including myocardial infarction34,35. Furthermore, a large cohort study indicated that apoA-1 can serve as indicators of coronary heart disease risk and targets for lipid-lowering therapy36. Glucose metabolism disorders can lead to more complex lipid metabolism abnormalities. A high-glucose environment, oxidative stress, and inflammation causing structural and functional impairments in mature ApoA-1, diminishing its regulatory effect on cholesterol metabolism and exacerbating atherosclerosis37,38,39. A comprehensive study revealed that Lower ApoA-1 levels have been linked to insulin resistance in individuals with impaired glucose tolerance40. Contrarily, ApoA-1 can enhance glycemic control in type 2 diabetes patients41, primarily through elevation of plasma insulin levels, improving pancreatic β-cell function, and enhancing insulin sensitivity for optimized glucose uptake in muscle and cardiac tissues 42,43,44,45.

A study involving 467 patients with ACS has identified the ratio of HbA1c/ApoA-1 as an independent predictor of all-cause mortality and MACEs in ACS patients, demonstrating significant prognostic value8,8. Nevertheless, the utility of HbA1c/ApoA-1 as an independent prognostic indicator in STEMI patients following PCI remains uncertain. Our investigation revealed higher HbA1c/ApoA-1 levels were observed in the MACEs group compared to non-MACEs individuals in STEMI patients post-PCI, thereby validating its role as a predictive risk factor for short-term MACEs. These findings align with previous studies; however, contrary to prior research, we observed a non-linear relationship between HbA1c/ApoA-1 and short-term MACEs in STEMI patients post-PCI. This discrepancy may be attributed to variations in population distribution, living environment, genetic characteristics, baseline attributes, and model calibration. The diverse factors influencing the progression towards clinical endpoints across different models warrant attention. Nonetheless, these observations hold significant implications for early identification of individuals at risk of experiencing MACEs.Although this study presents valuable insights, several limitations should be acknowledged. Residual confounders may impact observational study outcomes, and limitations in conducting time-dependent analyses due to dynamic HbA1c and ApoA-1 levels are evident as only baseline values were obtained. Additionally, the single-center design, small sample size, and short follow-up period call for caution in generalizing the findings. Further validation through larger multi-center studies is therefore recommended to strengthen the study conclusions.

Method

Study population

The research study received approval from the ethics committee of The Second Affiliated Hospital of Xi’an Jiao Tong University (2023083), and informed consent was obtained from all patients. A total of 182 consecutive STEMI patients undergoing PCI at the hospital between January 2022 and December 2023 were included in the analysis. The inclusion criteria were: (1) aged at least 18 years old, (2) diagnosed with STEMI and were undergoing PCI, in accordance with the diagnostic criteria of the 2019 Guidelines for the Diagnosis and Treatment of acute STEMI Infarction of the Chinese Society of Cardiology9, (3) all PCI procedures and medications administrations adhered to relevant guidelines, and complete clinical data were required for inclusion10. The exclusion criteria were: (1) patients with severe hepatic and renal insufficiency; (2) patients with malignant tumors and severe infectious diseases; (3) patients who underwent plain balloon angioplasty or coronary angiography without stent placement, and those lost to follow-up post-discharge were excluded. Cardiologists confirmed the medical histories and diagnoses of all patients, and perioperative and postoperative treatments were administered based on the attending cardiologist’s discretion.

Data collection and divide into groups

Data on the demographic characteristics, clinical, and laboratory information of all patients were extracted from the hospital information system, comprising details such as demographic profiles, laboratory results, and PCI-related specifics. Collected patient clinical data included gender, age, medical history (hypertension, diabetes, cerebral infarction, and prior PCI, smoking and drinking ), Killip cardiac function grade, preoperative TIMI blood flow grade, number of coronary artery lesions, systolic/diastolic blood pressure, left ventricular ejection fraction, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, and comprehensive venous blood analyses upon hospital admission covering blood tests, amino terminal brain natriuretic peptide precursor, and hypersensitive troponin T. Laboratory assessments, including liver and kidney function evaluations, lipid profiles, fasting glucose levels, HbA1c, and other parameters, were conducted on the second day of admission, alongside in-hospital medication administration. 2) Short-term prognosis: The occurrence of MACEs within six months post-discharge were recorded, MACEs comprising cardiac death, recurrent myocardial infarction, target vessel revascularization, recurrent angina pectoris, heart failure, and non-fatal stroke. Patients were categorized based on MACE occurrence into a good prognosis group (n = 132, no MACEs) and a poor prognosis group (n = 50, MACEs present).

Statistical analysis

Statistical analyses were conducted using SPSS version 27.0. Normally distributed measurement data were presented as mean ± standard deviation (SD), with group comparisons analyzed using the t-test. Non-normally distributed data were expressed as the median (interquartile range), and intergroup comparisons were performed using the rank-sum test. Categorical variables were assessed using chi-square or Fisher’s exact tests and presented as frequencies and percentages. whereas comparisons of categorical variables were conducted by using chi-square or Fisher’s exact test presented as frequencies and percentages. Variables with a significance level of P < 0.05 in single-factor logistic regression were incorporated into the multi-factor logistic regression analysis, adjusting for age, gender, smoking, alcohol consumption, hypertension, diabetes, previous cerebral infarction, Killip cardiac function grade, and statin usage. Subgroup analyses were conducted to validate the findings. Moreover, the ROC curve and AUC value were utilized to assess the predictive capacity of HbA1c/ApoA-1 for MACEs occurrence. The RCS model illustrated a non-linear correlation between HbA1c/ApoA-1 ratio and MACE incidence, analyzed using R version 4.2.2 software. A significance level of P < 0.05 was considered statistically significant.

Conclusions

In conclusion, HbA1c/ApoA-1, which can be readily obtained without additional cost, serves as an independent risk factor for short-term MACEs in patients with STEMI following PCI. It offers significant predictive value, enabling the early identification of high-risk groups and anticipation of MACE occurrences.