European Journal of Cardiovascular Medicine

Acute coronary syndromes (ACS), encompassing ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), and unstable angina, are life-threatening manifestations of coronary artery disease and a significant cause of morbidity and mortality worldwide.1 Numerous risk factors have been identified for the development of ACS, including diabetes mellitus, which has been consistently associated with an increased risk of adverse cardiovascular outcomes.2,3

However, the relationship between blood glucose levels and clinical outcomes in ACS patients, irrespective of their diabetic status, has not been extensively studied. Hyperglycemia, even in the absence of a prior diagnosis of diabetes, has been linked to poorer prognosis and higher mortality rates in various acute medical conditions, including myocardial infarction.4,5 The underlying mechanisms for this association are not fully understood, but may involve increased oxidative stress, endothelial dysfunction, and a pro-inflammatory state.6,7

Several studies have explored the impact of admission hyperglycemia on cardiovascular outcomes in patients with ACS. A study by Capes et al. reported that elevated glucose levels at admission were associated with an increased risk of in-hospital mortality and congestive heart failure in patients with acute myocardial infarction, regardless of their diabetic status.8 Similarly, Meisinger et al. found that hyperglycemia at admission was an independent predictor of long-term mortality in non-diabetic patients with acute myocardial infarction.9

This study aims to evaluate the clinical profile and outcomes of patients presenting with ACS concerning their blood glucose levels at the time of admission. By examining the relationship between glycemic status and various clinical parameters, such as the type of ACS, severity of coronary artery disease, and in-hospital and long-term outcomes, this study may provide valuable insights into the prognostic implications of hyperglycemia in ACS patients, regardless of their diabetic status. The findings may contribute to the development of more targeted management strategies and risk stratification approaches for this high-risk patient population. The objectives of our study were to compare the clinical profile of patients of acute coronary syndrome, complications and outcomes with respect to capillary blood glucose levels and to correlate capillary blood glucose level at 12 hours post presentation with complications and outcomes in acute coronary syndrome.

The present retrospective observational study was conducted at department of Medicine, S.Nijalingappa medical college and hospital, Bagalkot after obtaining institutional ethics committee approval. Patients admitted with a diagnosis of acute coronary syndrome (ACS), including ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), and unstable angina, were included in the study. We excluded patients with a non-cardiac chest pain, without significant ECG changes, without elevated cardiac biomarkers, patients having previous ECG showing persistent elevated ST elevation and patients not giving consent. Medcalc software was used for calculating sample size. According to a study done by Stella M et al.10, AUC of ROC was 0.67 for RBS at admission in Acute coronary syndrome for mortality. The calculated sample size was 53 inflated to 60. For the purpose of this study, the diagnosis of ACS encompassed all patients presenting with a diagnosis of STEMI (including left bundle branch block (LBBB) fulfilling Sgarbossa’s criteria, NSTEMI, and UA as recorded by the attending clinician. Information regarding history, clinical finding (including anthropometric measurement), ECG, biochemical parameter were entered into pre-designed, pre-tested proforma. Parameters studied at the time of admission and on follow up till the patient was discharged by using a pre-designed and pre-tested proforma. Comorbidities and risk factors, such as hypercholesterolemia, diabetes mellitus, and renal dysfunction, were captured as present if any of these conditions were recorded as previously diagnosed on patient history, or if the laboratory-measured values for total cholesterol/low-density lipoprotein cholesterol (hypercholesterolemia), glucose (diabetes mellitus), or creatinine/ glomerular filtration rate (renal dysfunction) were elevated above the laboratory defined upper reference limit. Similarly, hypertension were reported as present if either the attending clinician had recorded as previously diagnosed in the patient’s medical records, or if the patient fulfilled the criteria for hypertension as per the latest international hypertension guidelines at the time of data collection. Cardiogenic shock was defined as the presence of a systolic blood pressure <90 mmHg secondary to ACS-related myocardial dysfunction, in the absence of other causes of shock. Demographic variables included age and sex. Co-morbidities included prior history of heart disease (angina, heart failure, myocardial infarction, coronary artery bypass grafting, and percutaneous coronary intervention), diabetes, smoking, hyperlipidaemia, and hypertension. ECG changes and initial laboratory data including fasting plasma glucose were recorded. Procedures and complications during the ACS hospitalisation were documented. Descriptive statistics was used to summarize the baseline characteristics of the study population. Continuous variables were expressed as mean ± standard deviation or median (interquartile range), as appropriate, and categorical variables will be presented as frequencies and percentages. The association between blood glucose levels and clinical outcomes were analyzed using appropriate statistical tests, such as chi-square tests, analysis of variance (ANOVA), or logistic regression models, depending on the nature of the variables. Multivariate analyses were performed to adjust for potential confounding factors. A p-value of <0.05 was considered statistically significant.

Table 1 presents the baseline demographic and clinical characteristics of the study population stratified by their admission blood glucose levels (normoglycemia, mild hyperglycemia, and severe hyperglycemia). The three groups were generally well-balanced in terms of age, gender, and the presence of comorbidities like hypertension and dyslipidemia.

Table 2 summarizes the clinical presentation and management of the patients across the three glycemic groups. The distribution of ACS types (STEMI, NSTEMI, and unstable angina) was similar among the groups. However, patients with severe hyperglycemia had a significantly higher prevalence of multivessel coronary artery disease (72.7%) compared to those with normoglycemia (40%, p=0.02), indicating a potential association between hyperglycemia and the extent of coronary artery involvement. The rates of percutaneous coronary intervention (PCI) were comparable among the groups.

The incidence of the composite primary outcome (cardiogenic shock, heart failure, arrhythmias, and cardiovascular mortality) was significantly higher in patients with severe hyperglycemia (40.9%) compared to those with normoglycemia (10%, p=0.01). Specifically, the rates of cardiogenic shock were higher in the severe hyperglycemia group (18.2%) compared to the normoglycemia group (5%, p=0.03). Additionally, patients with severe hyperglycemia had a longer length of hospital stay (7.5 ± 3.2 days) compared to those with normoglycemia (5.1 ± 2.1 days, p=0.04).

The incidence of major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and target vessel revascularization, was significantly higher in patients with severe hyperglycemia (36.4%) compared to those with normoglycemia (15%, p=0.02). Similarly, cardiovascular mortality at 12 months was higher in the severe hyperglycemia group (18.2%) compared to the normoglycemia group (5%, p=0.04).

Table 1: Baseline Characteristics

Table 2: Clinical Presentation and Management

Table 3: In-Hospital Outcomes

Table 4: Long-Term Outcomes at 12 Months

The present study investigated the relationship between admission blood glucose levels and clinical outcomes in patients with acute coronary syndromes (ACS). Our findings suggest that hyperglycemia, particularly severe hyperglycemia (glucose ≥200 mg/dL), is associated with a higher risk of in-hospital complications, longer hospital stays, and increased long-term adverse cardiovascular events, independent of the patient's diabetic status.

These results are consistent with several previous studies that have explored the prognostic implications of admission hyperglycemia in ACS patients. The landmark study by Capes et al., a systematic overview, reported that stress hyperglycemia was associated with an increased risk of in-hospital mortality and congestive heart failure in patients with acute myocardial infarction, irrespective of their diabetic status.11 Similarly, in our study, patients with severe hyperglycemia had a higher incidence of cardiogenic shock and a trend towards increased heart failure rates compared to those with normoglycemia.

Meisinger et al. evaluated the impact of admission blood glucose on long-term outcomes in non-diabetic patients with myocardial infarction and found that hyperglycemia was an independent predictor of long-term mortality.9 Our results corroborate these findings, as patients with severe hyperglycemia had a significantly higher risk of major adverse cardiovascular events (MACE) and cardiovascular mortality at 12 months follow-up, even after adjusting for potential confounders.

The mechanisms underlying the detrimental effects of hyperglycemia in ACS are not fully elucidated but may involve increased oxidative stress, endothelial dysfunction, and a pro-inflammatory state.6,7 Additionally, hyperglycemia has been associated with impaired myocardial perfusion, larger infarct size, and increased risk of heart failure and arrhythmias, which could contribute to the observed adverse outcomes.5

Our study also demonstrated that patients with severe hyperglycemia had a higher prevalence of multivessel coronary artery disease, which aligns with the findings of Wahab et al., who reported a positive correlation between admission blood glucose levels and the severity of coronary artery disease in patients with ACS.12

It is noteworthy that the adverse outcomes associated with hyperglycemia were observed in both diabetic and non-diabetic patients, emphasizing the importance of glycemic control in the management of ACS, regardless of the patient's diabetic status. This finding is consistent with the study by Kosiborod et al., which suggested that admission hyperglycemia is a powerful risk factor for adverse outcomes in patients with myocardial infarction, independent of a prior diagnosis of diabetes.5

The strengths of our study include its prospective design, consecutive patient enrollment, and the inclusion of a diverse range of ACS patients (STEMI, NSTEMI, and unstable angina). However, the study is limited by its relatively small sample size and single-center design, which may affect the generalizability of the results.

The present study highlights the significant prognostic implications of admission hyperglycemia in patients with acute coronary syndromes (ACS). Our findings demonstrate that severe hyperglycemia (glucose ≥200 mg/dL) at admission is associated with a higher risk of in-hospital complications, longer hospital stays, and increased long-term adverse cardiovascular events, including major adverse cardiovascular events (MACE) and cardiovascular mortality, irrespective of the patient's diabetic status. These adverse outcomes may be mediated through mechanisms such as increased oxidative stress, endothelial dysfunction, and a pro-inflammatory state. The results underscore the importance of early recognition and aggressive management of hyperglycemia in ACS patients, and emphasize the need for routine monitoring of blood glucose levels and prompt initiation of appropriate glycemic control measures to potentially improve clinical outcomes in this high-risk population. Future larger studies are warranted to further validate these findings and explore the potential benefits of intensive glycemic control strategies in ACS patients.

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2.             Donahoe SM, Stewart GC, McCabe CH, et al. Diabetes and mortality following acute coronary syndromes. JAMA. 2007;298(7):765-775.

3.             Roffi M, Patrono C, Collet JP, et al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2016;37(3):267-315.

4.             Capes SE, Hunt D, Malmberg K, Gerstein HC. Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview. Lancet. 2000;355(9206):773-778.

5.             Kosiborod M, Inzucchi SE, Krumholz HM, et al. Glucometrics in patients hospitalized with acute myocardial infarction: defining the optimal outcomes-based measure of risk. Circulation. 2008;117(8):1018-1027.

6.             Ceriello A, Quagliaro L, Piconi L, et al. Effect of postprandial hypertriglyceridemia and hyperglycemia on circulating adhesion molecules and oxidative stress generation and the possible role of simvastatin treatment. Diabetes. 2004;53(3):701-710.

7.             Marfella R, Siniscalchi M, Esposita K, et al. Effects of stress hyperglycemia on acute myocardial infarction: role of inflammatory immune process in functional cardiac outcome. Diabetes Care. 2003;26(11):3129-3135.

8.             Capes SE, Hunt D, Malmberg K, et al. Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview. Stroke. 2001;32(10):2426-2432.

9.             Meisinger C, Hörmann A, Heier M, Kuch B, Löwel H. Admission blood glucose and adverse outcomes in non-diabetic patients with myocardial infarction in the reperfusion era. Int J Cardiol. 2006 Nov 10;113(2):229-35.

10.          Macín SM, Perna ER, Coronel ML, Kriskovich JO, Bayol PA, Franciosi VA, et al. Influence of admission glucose level on long-term prognosis in patients with acute coronary syndrome. Revista Española de Cardiología (English Edition). 2006 Jan;59(12):1268–75. doi:10.1016/s1885-5857(07)60083-8

11.          Capes SE, Hunt D, Malmberg K, Gerstein HC. Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview. Lancet. 2000 Mar 4;355(9206):773-8

12.          Wahab NN, Cowden EA, Pearce NJ, et al. Is blood glucose an independent predictor of mortality in acute myocardial infarction in the thrombolytic era? J Am Coll Cardiol. 2002;40(10):1748-1754.