European Journal of Cardiovascular Medicine

Acute Myocardial Infarction (AMI) remains a leading cause of morbidity and mortality worldwide, necessitating the identification of prognostic indicators that can guide early risk stratification and management strategies. Among these indicators, admission hyperglycemia in non-diabetic individuals has garnered significant attention due to its potential role in adverse cardiovascular outcomes. Although hyperglycemia is a well-established risk factor in diabetic patients with AMI, its prognostic implications in non-diabetic individuals remain an area of active investigation.

Admission hyperglycemia in non-diabetic patients with AMI is hypothesized to be a consequence of stress-induced catecholamine and cortisol release, leading to transient insulin resistance and impaired glucose metabolism¹. Studies suggest that stress hyperglycemia may reflect an exaggerated inflammatory and neurohormonal response, contributing to increased myocardial injury, impaired left ventricular function, and higher in-hospital mortality². Additionally, hyperglycemia has been associated with endothelial dysfunction, oxidative stress, and prothrombotic states, further exacerbating myocardial ischemia and reperfusion injury³.

Several observational studies have reported a strong correlation between elevated admission glucose levels and adverse cardiovascular outcomes in non-diabetic AMI patients⁴. However, discrepancies exist in defining hyperglycemia cut-offs, adjusting for confounding variables, and differentiating between transient stress hyperglycemia and prediabetic states. The absence of standardized thresholds for defining admission hyperglycemia complicates its utility as a prognostic biomarker⁵.

Given these considerations, this study aims to systematically analyze the prognostic effects of admission hyperglycemia in non-diabetic individuals with AMI. By evaluating its association with short- and long-term outcomes, we seek to clarify its clinical significance and provide evidence-based insights for risk stratification and therapeutic interventions.

Study Design and Setting

This study is an observational study conducted at a tertiary care hospital over a period of 24 months. The study included non-diabetic patients presenting with acute myocardial infarction (AMI) to the emergency department and cardiology unit.

Study Population

Inclusion Criteria

• Patients aged ≥18 years diagnosed with AMI (ST-elevation myocardial infarction [STEMI] or non-ST elevation myocardial infarction [NSTEMI]) based on clinical symptoms, electrocardiographic findings, and elevated cardiac biomarkers.
• Patients with no prior history of diabetes mellitus, confirmed by medical records and HbA1c <6.5% at admission.
• Patients presenting within 12 hours of symptom onset.

Exclusion Criteria

• Patients with known diabetes mellitus or HbA1c ≥6.5%.
• Patients with sepsis, chronic liver disease, chronic kidney disease, or active malignancy.
• Patients on chronic steroid therapy or other drugs influencing glucose metabolism.
• Patients with incomplete data or those who refused consent.

Sample Size Estimation

The sample size was calculated based on the expected prevalence of admission hyperglycemia in non-diabetic AMI patients and its association with in-hospital mortality. The estimated sample size per group was 118 patients. After adjusting for a 10% dropout rate, the final sample size was determined to be 260 patients (130 per group).

Data Collection and Variables

On admission, demographic and clinical data, including age, sex, comorbidities, and vital parameters, were recorded. Laboratory investigations were performed within the first hour of admission, including:

• Blood Glucose Levels: Fasting and random blood glucose levels measured using standard enzymatic methods. Hyperglycemia was defined as admission blood glucose ≥140 mg/dL.
• HbA1c: Measured to rule out undiagnosed diabetes.
• Cardiac Biomarkers: Troponin I/T and creatine kinase-MB (CK-MB).
• Inflammatory Markers: C-reactive protein (CRP) and white blood cell (WBC) count.
• Echocardiography: Left ventricular ejection fraction (LVEF) assessment within 24 hours of admission.

Outcomes Assessed

Primary and secondary outcomes were analyzed to evaluate the prognostic significance of admission hyperglycemia.

• Primary Outcome: In-hospital mortality.
• Secondary Outcomes:
• Major adverse cardiac events (MACE) including heart failure, arrhythmias, cardiogenic shock, and reinfarction.
• Length of hospital stay.
• 30-day and 6-month mortality rates.

Statistical Analysis

Data were analyzed using SPSS version 25.0 (IBM Corp., Armonk, NY). Continuous variables were expressed as mean ± standard deviation (SD) and compared using the independent t-test or Mann-Whitney U test, as appropriate. Categorical variables were presented as frequencies and percentages and analyzed using the chi-square test or Fisher’s exact test. A logistic regression model was applied to identify independent predictors of mortality and MACE. Statistical significance was set at p < 0.05.

Ethical Considerations

The study was approved by the Institutional Ethics Committee, and written informed consent was obtained from all participants before enrollment. Patient confidentiality was maintained in compliance with the Declaration of Helsinki.

Table 1: Baseline Characteristics of the Study Population

The hyperglycemia group had a significantly higher mean age compared to the normoglycemia group (p = 0.034). Admission glucose levels were significantly higher in the hyperglycemia group (p < 0.001). No significant differences were observed in sex distribution, hypertension, hyperlipidemia, smoking status, BMI, and HbA1c levels between the two groups.

Table 2: Cardiac and Laboratory Findings

The hyperglycemia group had significantly higher Troponin I levels, CK-MB, CRP, and WBC count, suggesting greater myocardial injury and inflammatory response (p < 0.05 for all). The mean LVEF (%) was significantly lower in the hyperglycemia group (p < 0.001), indicating poorer cardiac function.

Table 3: Clinical Outcomes

In-hospital mortality was significantly higher in the hyperglycemia group (16.9% vs. 6.2%, p = 0.009). The hyperglycemia group had a higher incidence of heart failure (23.1% vs. 10.8%), arrhythmias (18.5% vs. 9.2%), cardiogenic shock (13.8% vs. 5.4%), and reinfarction (10.8% vs. 3.8%), all statistically significant (p < 0.05). The mean length of hospital stay was significantly longer in the hyperglycemia group (7.3 ± 3.2 days vs. 5.7 ± 2.1 days, p = 0.004), indicating a more complicated clinical course.

The present study highlights the significant impact of hyperglycemia on myocardial injury, inflammatory response, and clinical outcomes in patients with acute coronary syndrome (ACS).

Our study population was well-matched in terms of demographic and clinical characteristics, with no significant differences in sex distribution, hypertension, hyperlipidemia, smoking status, BMI, or HbA1c levels between the normoglycemia and hyperglycemia groups. However, the hyperglycemia group was slightly older (p = 0.034), which may have influenced the severity of outcomes. Importantly, admission glucose levels were significantly higher in the hyperglycemia group (p < 0.001), reinforcing the study's focus on the impact of acute hyperglycemia.

Elevated cardiac biomarkers, including Troponin I and CK-MB, were observed in the hyperglycemia group (p = 0.012 and p = 0.008, respectively), indicating greater myocardial damage. Additionally, CRP and WBC counts were significantly higher (p = 0.002 and p = 0.015, respectively), suggesting a more pronounced inflammatory response. These findings align with previous studies indicating that hyperglycemia exacerbates oxidative stress, endothelial dysfunction, and inflammatory pathways, leading to increased myocardial injury and poorer cardiac function.^1,2

LVEF was significantly lower in the hyperglycemia group (45.8% vs. 51.4%, p < 0.001), reflecting a compromised left ventricular systolic function. This decline in cardiac function could contribute to the observed higher rates of heart failure and cardiogenic shock.⁶

The study demonstrated that hyperglycemia is a strong predictor of adverse clinical outcomes in ACS patients. In-hospital mortality was significantly higher in the hyperglycemia group (16.9% vs. 6.2%, p = 0.009), which is consistent with previous literature linking hyperglycemia to increased mortality in myocardial infarction.⁷ The rates of heart failure (p = 0.005), arrhythmias (p = 0.021), cardiogenic shock (p = 0.032), and reinfarction (p = 0.027) were also significantly higher in the hyperglycemia group, emphasizing the detrimental effects of elevated glucose levels during acute cardiac events.^8,5

Furthermore, the length of hospital stay was significantly prolonged in hyperglycemic patients (7.3 ± 3.2 vs. 5.7 ± 2.1 days, p = 0.004), indicating a more complicated clinical course and increased healthcare burden. These findings highlight the need for improved glycemic control strategies to mitigate adverse outcomes.⁹

Given the strong association between hyperglycemia and poor outcomes, early identification and management of hyperglycemia in ACS patients are critical. Intensive glucose control protocols and targeted interventions may help reduce myocardial damage and improve clinical outcomes.¹⁰ Future studies should explore optimal glucose management strategies, considering the potential risks of hypoglycemia with aggressive glucose-lowering therapies.^11,12

In summary, our study underscores the detrimental impact of hyperglycemia on myocardial injury, inflammatory response, and clinical outcomes in ACS patients. Hyperglycemia was associated with increased in-hospital mortality, higher rates of complications, and longer hospital stays. These findings highlight the importance of stringent glycemic control in ACS patients to improve prognosis and reduce adverse events

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