European Journal of Cardiovascular Medicine

Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, with coronary artery disease (CAD) accounting for a significant proportion of these deaths. Among acute coronary syndromes, ST-elevation myocardial infarction (STEMI) represents one of the most severe and life-threatening manifestations, necessitating urgent revascularization to reduce infarct size and improve survival.^1,2 Despite substantial improvements in early percutaneous coronary intervention (PCI), antithrombotic therapies, and intensive cardiac care over recent decades, STEMI continues to be associated with considerable in-hospital complications such as acute heart failure and death, posing challenges to patient management and prognosis.^3,4 Hyperglycemia at admission is a common finding among STEMI patients, occurring in both diabetic and non-diabetic populations, and has been consistently associated with adverse clinical outcomes including increased risk of heart failure, arrhythmias, cardiogenic shock, and in-hospital mortality.^5,6 This phenomenon, termed stress hyperglycemia, reflects an acute elevation in blood glucose levels triggered by a surge in counter-regulatory hormones such as catecholamines, cortisol, and glucagon during periods of physiological stress, such as acute myocardial infarction.^7,8 The resulting hyperglycemic state may exacerbate myocardial injury through oxidative stress, endothelial dysfunction, and pro-inflammatory pathways, compounding the underlying ischemic insult and worsening patient outcomes.⁹ However, reliance on a single admission glucose value as a prognostic marker is limited by its inability to differentiate between acute stress-induced hyperglycemia and chronic poor glycemic control, potentially misclassifying risk and leading to suboptimal therapeutic decisions.^7,10 To address this, the concept of the glycemic gap has emerged as a more refined biomarker, defined as the difference between the admission plasma glucose and the estimated average glucose derived from glycated hemoglobin (HbA1c) measurements.¹¹ By adjusting for baseline glycemic status, glycemic gap captures the acute deviation from an individual's chronic glucose levels, thus providing a clearer reflection of stress hyperglycemia severity in acute illnesses. The prognostic value of glycemic gap has been explored in various critical conditions. In sepsis and intensive care settings, elevated glycemic gap has been linked to increased mortality, reflecting systemic inflammatory response and critical illness severity.¹² In acute cerebrovascular events, studies have demonstrated that higher glycemic gap values predict poor functional outcomes and in-hospital mortality among patients with ischemic stroke and intracerebral hemorrhage.^13,14 Within the cardiovascular domain, multiple studies have reported significant associations between elevated glycemic gap and adverse outcomes in acute coronary syndromes, including STEMI. Wu et al.¹⁵ found that higher glycemic gap values were independently linked to increased 30-day major adverse cardiovascular events and mortality among STEMI patients, regardless of diabetic status. Similarly, Liao et al.¹⁶ demonstrated that in diabetic patients with acute myocardial infarction, elevated glycemic gap was associated with higher rates of cardiogenic shock, heart failure, and in-hospital death. Despite these observations, evidence regarding the utility of glycemic gap as a predictor of in-hospital heart failure and mortality among first STEMI presentations remains limited and heterogeneous, particularly in South Asian populations where the burden of STEMI and its complications is high.¹⁷ Early identification of patients at risk of developing acute heart failure is critical for guiding intensive monitoring, timely initiation of heart failure therapies, and optimizing in-hospital outcomes. Therefore, this study aims to evaluate the association between glycemic gap and the development of in-hospital heart failure and mortality among patients presenting with their first ST-elevation myocardial infarction.

OBJECTIVES

To evaluate the association between glycemic gap and the development of in-hospital heart failure and mortality among patients presenting with their first STEMI.

This cross-sectional comparative type of observational study was conducted in Department of Cardiology, Mymensingh Medical College Hospital, Mymensingh, Bangladesh, during the period from October, 2019 to March, 2021. Total 287 patients aged 18 years and above presenting with their first episode of acute ST-elevation myocardial infarction (STEMI), admitted within 12 hours of chest pain onset, and availability of HbA1c and admission plasma glucose measurements within first 6 hours of admission were included in this study. Patients were excluded if they had a prior history of myocardial infarction, PCI, or coronary artery bypass grafting; known heart failure or cardiomyopathy; significant valvular or congenital heart disease; chronic kidney disease with an estimated glomerular filtration rate below 30 ml/min/1.73m²; severe systemic illness or sepsis; or if they refused to provide informed consent. Patients were managed by thrombolysis by streptokinase. All patients were divided into two groups: Group-I included patients with glycemic gap level >40 mg/dl and Group-II included patients with glycemic gap level ≤40 mg/dl. All patients underwent a detailed history and physical examination. Electrocardiography was performed immediately upon admission and patients were continuously monitored for arrhythmias throughout their hospital stay. Serum troponin-I was measured at admission or after four hours if the initial test was negative in cases of chest pain duration under four hours. Patients were followed during hospitalization for the development of adverse outcomes including acute heart failure, cardiogenic shock, major arrhythmias such as ventricular tachycardia, ventricular fibrillation, atrial fibrillation, or high-degree atrioventricular block, and in-hospital mortality. Ethical approval was obtained from the Institutional Review Board and informed written consent was secured from all participants prior to enrollment. Statistical analysis was performed using SPSS version 25.0. P value of less than 0.05 was considered statistically significant.

This cross-sectional comparative type of observational study was conducted in Department of Cardiology, Mymensingh Medical College Hospital, Mymensingh, Bangladesh, during the period from October, 2019 to March, 2021. Total 287 patients aged 18 years and above presenting with their first episode of acute ST-elevation myocardial infarction (STEMI), admitted within 12 hours of chest pain onset, and availability of HbA1c and admission plasma glucose measurements within first 6 hours of admission were included in this study. Patients were excluded if they had a prior history of myocardial infarction, PCI, or coronary artery bypass grafting; known heart failure or cardiomyopathy; significant valvular or congenital heart disease; chronic kidney disease with an estimated glomerular filtration rate below 30 ml/min/1.73m²; severe systemic illness or sepsis; or if they refused to provide informed consent. Patients were managed by thrombolysis by streptokinase. All patients were divided into two groups: Group-I included patients with glycemic gap level >40 mg/dl and Group-II included patients with glycemic gap level ≤40 mg/dl. All patients underwent a detailed history and physical examination. Electrocardiography was performed immediately upon admission and patients were continuously monitored for arrhythmias throughout their hospital stay. Serum troponin-I was measured at admission or after four hours if the initial test was negative in cases of chest pain duration under four hours. Patients were followed during hospitalization for the development of adverse outcomes including acute heart failure, cardiogenic shock, major arrhythmias such as ventricular tachycardia, ventricular fibrillation, atrial fibrillation, or high-degree atrioventricular block, and in-hospital mortality. Ethical approval was obtained from the Institutional Review Board and informed written consent was secured from all participants prior to enrollment. Statistical analysis was performed using SPSS version 25.0. P value of less than 0.05 was considered statistically significant.

RESULT

The baseline characteristics of the study population, comprising 287 patients with STEMI, are summarized in Table I. The mean age of patients in Group I (glycemic gap >40 mg/dl) was slightly higher at 55.36 ± 13.28 years compared to 53.06 ± 11.64 years in Group II (glycemic gap ≤40 mg/dl), though this difference was not statistically significant (p=0.07). Age distribution showed that most patients in both groups were within the 40–70 years range, with a small proportion over 70 years (9.4% in Group I vs. 1.9% in Group II). Males predominated in both groups, accounting for 86.7% in Group I and 84.3% in Group II, without significant difference (p=0.568). Regarding comorbidities, diabetes mellitus was more prevalent in Group I (38.28%) compared to Group II (13.2%), and systemic hypertension was observed in 53.9% of Group I and 32.1% of Group II patients. Dyslipidemia prevalence was comparable between the groups (27.3% in Group I and 32.7% in Group II). However, none of these differences reached statistical significance. Clinical parameter comparisons between groups are shown in Table II. Admission blood glucose was also significantly elevated in Group I (10.44 ± 4.35 mmol/L) relative to Group II (6.59 ± 1.46 mmol/L), p<0.001. HbA1c levels were higher in Group I (6.51 ± 5.6%) than Group II (5.35 ± 1.09%), although this was not statistically significant (p=0.34). Estimated average glucose was similar in both groups (105.99 ± 39.81 mg/dl in Group I vs. 105.27 ± 31.13 mg/dl in Group II, p=0.867). Group I had a significantly higher mean glycemic gap (85.86 ± 54.10 mg/dl) compared to Group II (13.49 ± 23.25 mg/dl) with p<0.001. Regarding the types of Acute Myocardial Infarction (AMI) observed among the study population (Figure 1), the distribution of infarct sites did not differ significantly between groups (p=0.867). Anterior STEMI was the most common presentation in both groups, observed in 32% of Group I and 26.4% of Group II patients. Inferior STEMI accounted for 22.7% in Group I and 28.3% in Group II, while anteroseptal, lateral, and infero-right ventricular infarctions showed comparable distributions across groups. Table III presents the comparison of in-hospital adverse outcomes between groups. The incidence of acute heart failure was significantly higher in Group I (60.2%) compared to Group II (28.3%) with p<0.001. Cardiogenic shock was also notably more frequent in Group I (35.16%) than Group II (17.75%), p<0.001. Conduction defects were observed in 11.72% of Group I and 6.92% of Group II patients (p=0.159). Arrhythmias, including ventricular tachycardia, ventricular fibrillation, or atrial fibrillation, occurred in 6.25% of Group I versus 2.36% of Group II (p=0.116). In-hospital mortality was significantly higher in Group I (13.28%) compared to Group II (5.66%) with a p-value of 0.025. Figure 2 demonstrates Pearson correlation coefficient test between heart failure and glycemic gap which showed positive relationship between heart failure and glycemic gap. Figure 3 showed Pearson correlation coefficient between in-hospital mortality and glycemic gap which presented positive relationship between in-hospital mortality and glycemic gap.

Table-I: Baseline characteristics of the study groups (N=287)

Table-II: Comparison of clinical parameters between the study groups (N=287)

Table-III: Comparison of in-hospital adverse outcomes between the study groups (N=287)

This prospective observational study evaluated the association between glycemic gap and in-hospital outcomes among patients presenting with first ST-elevation myocardial infarction (STEMI). The mean age of patients in the high glycemic gap group was slightly higher at 55.36 ± 13.28 years compared to 53.06 ± 11.64 years in the low glycemic gap group, although this difference was not statistically significant. Similar age distributions were reported by Wu et al.¹⁵ and Wei et al.¹⁸, who found mean ages ranging from 55 to 60 years in STEMI cohorts stratified by glycemic gap. Males predominated in both groups in this current study, accounting for over 85%, which aligns with previous findings demonstrating male predominance in STEMI patients.^15,19 Diabetes mellitus was more prevalent in the high glycemic gap group (38.28%) compared to the low glycemic gap group (13.2%), a trend consistent with studies by Garcia et al.⁷ and Ghanem et al.¹¹ that reported higher diabetes prevalence among patients with elevated glycemic gap. Hypertension and dyslipidemia frequencies in both groups were comparable to global STEMI registries, as shown by Wei et al.¹⁸. Clinical parameter comparisons showed that patients in the high glycemic gap group had a significantly higher mean glycemic gap (85.86 ± 54.10 mg/dl) compared to the low glycemic gap group (13.49 ± 23.25 mg/dl, p<0.001), with admission blood glucose also significantly elevated in the high glycemic gap group. These findings are in concordance with Wu et al.¹⁵, who reported mean glycemic gaps of 73.2 ± 56.4 mg/dl in the high group versus 11.8 ± 19.6 mg/dl in the low group, and significantly higher admission glucose among the high glycemic gap subgroup. HbA1c levels were slightly higher in the high glycemic gap group in this current study, though not statistically significant, consistent with findings by Wei et al.¹⁸, while estimated average glucose was similar across groups, further reinforcing the concept that glycemic gap captures acute hyperglycemia severity independent of chronic glycemic status.¹⁰ Regarding infarct site distribution, anterior STEMI was the most common presentation in both groups, observed in 32% of the high glycemic gap group and 26.4% of the low group, while inferior STEMI accounted for 22.7% and 28.3% respectively. Similar distributions were reported by Kwok et al.²⁰ and Liang et al.²¹, who identified anterior STEMI as the predominant presentation in global cohorts, with inferior infarctions as the second most frequent type. In terms of in-hospital adverse outcomes, this current study found that heart failure incidence was significantly higher in the high glycemic gap group (60.2%) compared to the low group (28.3%, p<0.001). Cardiogenic shock was also notably more frequent in the high glycemic gap group (35.16% vs. 17.75%, p<0.001). These findings are consistent with Wu et al.¹⁵, who demonstrated that higher glycemic gap was associated with increased rates of cardiogenic shock and heart failure in STEMI patients, and with Xu et al.²², who reported glycemic gap as an independent predictor of cardiogenic shock outcomes. Conduction defects and arrhythmias were more common in the high glycemic gap group in this current study, although not statistically significant, paralleling findings by Ghanem et al.¹¹ who reported increased but non-significant arrhythmia incidence in patients with elevated glycemic gap. Importantly, in-hospital mortality was significantly higher in the high glycemic gap group (13.28%) compared to the low glycemic gap group (5.66%, p=0.025), aligning with the results of Liao et al.¹⁶ and Wu et al.¹⁵, who demonstrated strong associations between elevated glycemic gap and increased in-hospital mortality risk. Furthermore, the Pearson correlation analysis showed a positive relationship between glycemic gap and heart failure as well as between glycemic gap and in-hospital mortality, underscoring its role as a prognostic marker. Similar positive correlations were reported by Zhu et al.²³, who demonstrated that higher glycemic gap values were significantly correlated with reduced left ventricular ejection fraction and increased heart failure incidence post-STEMI. Likewise, Ghanem et al.¹¹ and Garcia et al.⁷ found significant positive correlations between glycemic gap and both heart failure and mortality outcomes in ACS and STEMI patients. Overall, our findings support existing literature indicating that glycemic gap is a reliable marker reflecting acute hyperglycemia severity and is associated with adverse in-hospital outcomes including heart failure, cardiogenic shock, and mortality.

This study demonstrates that an elevated glycemic gap is significantly associated with higher rates of in-hospital heart failure, cardiogenic shock, and mortality among first ST-elevation myocardial infarction (STEMI) patients. Glycemic gap, reflecting acute stress hyperglycemia beyond chronic glycemic control, emerges as a simple, reliable prognostic marker to guide early risk stratification and optimize management strategies in acute STEMI care. The precise mechanisms for the association of acute hyperglycemia with increase in-hospital adverse outcome and the best management strategies are yet unclear and require further analysis. The association between glycemic gap, chronic blood glucose controls and the outcomes should be further explored in prospective longitudinal studies. Further prospective cohort study with larger sample size and longer follow up period is recommended to establish findings of our study.

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