A study of prognostic implications of admission hyperglycemia in non diabetic acute myocardial infarction patients

 

Sanjay Jagtap¹, Sham Toshniwal², Ankit Panjwani^3*

 

Abstract                                                                                                                                     Background: Elevated admission glucose levels in non diabetic patients with acute myocardial infarction are independently associated with large infarct sizes and a higher mortality rate when compared with patients with normal glucose levels. A strong correlation between glycaemia and shock or development of heart failure has also been reported. Aim and objectives: This study was conducted to assess the prognostic implications of admission hyperglycemia in non diabetic acute myocardial infarction patients. Methodology: The study was conducted on 150 non diabetic STEMI patients admitted in a tertiary hospital during 2018-2019. Patients with acute myocardial infarction proven by ECG, cardiac enzymes (Positive Troponin I or CPK-MB) and symptoms suggestive of acute myocardial infarction who have no previous history of diabetes with HbA1c <6.5 were included in the study. Results:Among patients with admission blood glucose ≤140 mg%, 6 patients (8.10%) developed cardiogenic shock, 4 patients (5.40%) developed arrhythmias, 3 patients (4.05%) developed AV block (≥2^nd degree) and 5 patients (6.75%) died during the hospital stay. Among patients with admission blood glucose >140 mg%,16 patients (21.05%) developed cardiogenic shock, 14 patients (18.42%) developed arrhythmias, 11 patients (14.47%) developed AV block and patients (14%) died during the hospital stay. The complications and mortality were significantly higher in patients with admission blood glucose >140 mg%. Conclusion: Hyperglycemia at admission in non diabetic patients of acute ST elevation myocardial infarction is strongly associated with higher in hospital complications like cardiogenic shock, arrhythmias and AV block and hospital stay mortality.

 

INTRODUCTION

Stress hyperglycemia represents increased blood glucose levels that is result of activation of neurohormonal processes in organism exposed to stress. Increased glucose level during stress is evoked by integrated hormonal, cytokine and nervous counterregulatory signals on glucose metabolic pathways and, therefore, presented in the same time with hyperinsulinemia and insulin resistance. The mortality and morbidity of a diabetic patient is poor as compared to non-diabetic patient.¹ Elevated admission glucose levels in non diabetic patients with acute myocardial infarction are independently associated with large infarct sizes and a higher mortality rate when compared with patients with normal glucose levels.² A strong correlation between glycaemia and shock or development of heart failure has also been reported.^3,4 Acute hyperglycaemia in healthy subjects and in patients with impaired glucose tolerance or overt diabetes produces a rise in inflammatory markers. Following this line of thought, it might be speculated that the detrimental effect of stress hyperglycaemia in acute MI might also stem from its ability to increase inflammation.

 

METHODOLOGY

The study was conducted on 150 non diabetic STEMI patients admitted in a tertiary hospital during 2018-2019.

• Inclusion criteria:
• Patients with acute myocardial infarction proven by
• ECG (ST segment elevation > 0.1mV in at least 2 contiguous leads)
• Cardiac enzymes (Positive Troponin I or CPK-MB)
• Symptoms suggestive of acute myocardial infarction who have no previous history of diabetes.
• Patients with HbA1c <6.5

 

• Exclusion criteria:
• Patients who present with Non-ST Elevation MI (NSTEMI)
• Patients with a previous history of diabetes mellitus.
• Patients receiving drugs that are known to elevate blood sugar levels (eg. Corticosteroids)
• Patients who received dextrose containing intravenous fluids before admission.
• Time from the beginning of symptoms to admission to Critical Care Unit more than 48 hrs.

A complete history of all patients was noted. All patients’ blood sample was collected on admission for estimating plasma glucose level. Complete general and systemic examination of the patients was done. ECG of all the patients were read and recorded. Patients were examined for complications of AMI including arrhythmias, cardiogenic shock, conduction abnormalities.

Patients were grouped in to TWO categories according to their admission blood glucose levels,

Group I: Blood glucose level ≤ 140 mg%,

Group II: If their blood glucose level is > 140 mg%.

The groups were compared to demonstrate correlation between stress hyperglycemia and cardiovascular outcomes of arrhythmias, cardiogenic shock, AV block and death. Normality of data was tested by Kolmogorov-Smirnov test. If the normality was rejected then non parametric test was used. Quantitative variables were compared using Independent t test/Mann-Whitney Test (when the data sets were not normally distributed) between the two groups. Qualitative variables were correlated using Chi-Square test/Fisher’s Exact test. Univariate and multivariate logistic regression was used to assess the significant risk factors of RBS>140. The data was entered in MS EXCEL spreadsheet and analysis was done using Statistical Package for Social Sciences (SPSS) version 21.0.

 

RESULTS

There were 74 patients in group I and 76 patients in group II.

Sex distribution:

There were total 90 males and 60 females in the study. Group I had 30 females and 44 males. Group II had 30 females and 46 males. There was no significant difference between the number of males and females in two groups (p= 0.894).

Age distribution

The mean age of patients in Group I and Group II were 62.45 ± 12.24 and 61.14 ± 11.35 respectively. Median age in group I and group II were 65 and 62 years respectively. There was no significant difference in patients’ mean age in between the groups (p= 0.608).

Personal and past history:

There were total 32 (21.33%) smokers in the study of which 18 were in group I and 14 in group II. History of smoking was present in 24.32% and 18.42% of patients of Group I and Group II respectively. There was no significant difference in number of smokers in between the two groups (p= 0.378). There were total of 46 patients with history of alcohol consumption in the study. Group I and Group II, both had 23 patients and there was no significant difference in number of patients with history of alcohol consumption between the two groups.

The history of hypertension was present in 45 patients of which 20 patients were in Group I and 25 patients in Group II. There was no statistically significant difference in number of hypertensives between the two groups.

 

Figure 1:

 

HbA1c levels

Mean HbA1c level in group I and group II were 5.46 and 5.5 respectively. The difference between them was insignificant (p= 0.475) indicating that patients in both the groups had similar glycemic status prior to myocardial infarction and the hyperglycemic response was secondary to stress.

General physical examination

 

Table 1:

 

This table shows mean heart rate, systolic blood pressure and diastolic blood pressure between the two groups. There was a statistically significant difference in heart rate, SBP and DBP between the two groups.

 

Development of complications:

Total 14.66% of patients developed cardiogenic shock. 6 patients (8.10%) in group I and 16 patients (21.05%) in group II developed cardiogenic shock. There was statistically significant (p= 0.025) increase in number of patients developing cardiogenic shock in group II. A total of 18 patients developed arrhythmias of which 4 patients (5.40%) were in group I and 14 patients (18.42%) in group II. There was a statistically significant increase in number of patients with arrhythmias in group II (p= 0.022). Total 14 patients (9.33%) in the study developed an AV block of ≥2^nd degree. 3 patients (4.05%) in group I developed AV block (≥2^nd degree) and 11 patients (14.47%) in group II developed AV block. There was a statistically significant (p=0.046) increase in patients developing AV block in group II.

 

Figure 2:

Total 21 patients (14%) died during the hospital stay. 5 patients (6.75%) from group I died during hospital stay while 16 (21%) patients from group II died during hospital stay. There was a statistically significant (p= 0.012) increase in hospital stay mortality in group II patients. Univariate logistic regression analysis was carried out to adjust the effect of confounding factors. It was found that hyperglycemia was associated with heart rate, SBP, DBP, cardiogenic shock, arrhythmias, AV block and death.

 

DISCUSSION

Mean age of patients in the present study was 61.79 ± 11.78 years. Mean age of patients in the study by Rafael et al..² on 834 patients was 64 ± 13 years. Mean age in the present study was close to the literature There were 32 smokers, 45 hypertensives and 46 patients with history of alcoholism. There was no significant difference in the number of smokers, hypertensives and alcoholics in between the two groups. Hence, both the groups were similar regarding distribution of risk factors. The mean heart rate in the present study was 79.39 ± 13.34 bpm. The mean heart rate in the study by Rafael et al.² was 79 ± 22 bpm which is close to the present study. The mean heart rate in group I was 76.88 ± 12.75 bpm and in group II was 81.83 ± 13.52 bpm in the present study. There was a statistically significant increase in heart rate in group II i.e. patients with hyperglycemia. This is in concordance with the previous studies by Kadri et al.. and Suleiman et al.. and Modenesi et al..^5-7 The probable explanation for this might be increased sympathetic tone in patients with stress hyperglycemia. There was a statistically significant fall in both SBP (p=0.004) and DBP (p<0.001) in group II patients as compared to group I patients. Probable explanation for this might be due to the reason that studies have reported that patients with stress hyperglycemia have poor LV function and lower ejection fraction.⁵ Previous studies have reported similar results with respect to mean SBP and DBP.^5,6 Incidence of cardiogenic shock, arrhythmias and AV block (≥2^nd degree) was found to be significantly greater among stress hyperglycemic patients. Kadri et al.⁵, Modenesi et al.⁸, Zhou Na et al..⁷, Rafael et al.² and Aggarwal et al..⁹ also found significantly higher incidence of these complications in hyperglycemic patients which was consistent with our study. The hospital stay mortality was 6.75% in group I and 21.05% in group II patients which was statistically significant indicating stress hyperglycemia to be an indicator of hospital stay mortality. The mortality in the studies by Suleiman et al..⁶ and Timmer et al..¹⁰ were 29% and 36% in the hyperglycemic group which were relatively higher as compared to other studies due to the fact that they refer to 30-day mortality and 8-year mortality respectively. Rest of the studies indicate in hospital mortality which was significantly higher in hyperglycemic group being consistent with the findings of the present study. The exact mechanism through which hyperglycemia worsens the prognosis of ischemic patients has not been well established. Its pathophysiology is believed to be based on endothelial and microvascular dysfunction, causing a prothrombotic state produced by vascular inflammation. The endothelial dysfunction inactivates nitric oxide and increases oxidative stress, responsible for the production of oxygen reactive species¹¹. The production of those radicals activates transcription and growth factors and secondary mediators. Through direct tissue lesion or activation of those secondary mediators, hyperglycemia-induced oxidative stress causes additional lesion to myocytes.^11,12 There is evidence that the prothrombotic state generated by hyperglycemia originates from reduced plasma fibrinolytic activity and action of tissue plasminogen activator.¹³

 

CONCLUSION

Hyperglycemia at admission in non diabetic patients of acute ST elevation myocardial infarction is strongly associated with higher in hospital complications like cardiogenic shock, arrhythmias and AV block. Hyperglycemia at admission is a strong predictor of early mortality during hospital stay. Though hyperglycemia at admission is a strong predictor of in hospital complications and mortality, it is not an independent predictor of either of them. Stress hyperglycemia is also associated with significantly lower systolic and diastolic blood pressure and higher heart rate at admission.

 

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