Introduction
Hyperglycemia was reported to deteriorate myocardial function in the setting of ischemia as it causes oxidative stress, stimulates apoptosis, and activates coagulation pathway1.
In clinical practice, glycated hemoglobin (HbA1c) is used as a measure of chronic hyperglycemia2. However, it remains unclear how chronic hyperglycemia affects short-term outcomes in patients with acute myocardial infarction (AMI)2.
Despite the advances in the management of AMI, ST-segment elevation myocardial infarction (STEMI) continues to be a major health problem worldwide and its fatality is in the first initial hours3.
The aim of this study was to evaluate the impact of chronic hyperglycemia on in-hospital and short-term outcome in patients with the first acute anterior myocardial infarction (MI) treated with streptokinase as reperfusion therapy.
Materials and methods
It was a single-center, prospective, cross-sectional study that was conducted at the coronary care unit of Benha University Hospital, Egypt, during the period from December 2017 to September 2018. A total of 100 patients with the first acute anterior STEMI treated with streptokinase were enrolled in the study. They were classified according to the level of admission HbA1c into two groups: chronic hyperglycemic group (HbA1c ≥ 6.5%) and non-chronic hyperglycemic group (Hb1Ac < 6.5%). An informed consent was signed from all patients after its approval from the local ethics committee.
Patients with cardiogenic shock at presentation, contraindications to thrombolytic therapy, prior ischemic heart disease, rhythm other than sinus rhythm, and poor echogenicity were excluded from the study.
Laboratory investigation
Random blood sugar, HbA1c, cardiac enzymes (troponin and CKMB), and creatinine were done to all patients.
Echocardiography
All echocardiographic parameters were done during hospital admission by two experienced cardiologists blinded to patient clinical data. All examinations were done using the commercially available system (Vivid 7, GE Ultrasound, Horten, Norway). The left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and left ventricular ejection fraction (LVEF) were assessed using modified biplane Simpsons method4. After 6-month follow-up, the left ventricular (LV) volumes were reassessed and compared to baseline data to detect LV remodeling; defined by significant LV volume dilatation (> 20%) compared to baseline measurements5. Tissue Doppler imaging was used to assess systolic (S) wave and diastolic waves (é and a`)6. Speckle tracking echocardiography (STE) and three consecutive cardiac cycles with frame rate of 60-90 frames/s in the apical three, four, and two chamber views were used. The LV endocardial border was traced at end systole after identification of 3 points (basal septal, basal lateral, and apical), and the automatically created region of interest was manually adjusted to the thickness of the myocardium. Segments were discarded if tracking was of persistent poor quality following readjustment of the region of interest. Subsequently, numeric and graphical bulls eye displays of deformation parameters were automatically generated for all LV segments to obtain global longitudinal strain (GLS). Aortic valve closure was defined in the apical long-axis view, and the interval between the R wave and this time point was then automatically measured to serve as a reference for identification of end systole7.
Outcome
Patients were followed up in-hospital and for 6 months post-discharge, for the development of any major adverse cardiac events (MACEs) including; death, heart failure, reinfarction, arrhythmias, stroke, bleeding, and LV remodeling.
Statistical analysis
Data management was performed using Statistical Package for the Social Sciences (SPSS) program version 20 (SPSS, Chicago, IL, USA). Continuous variables were expressed as mean and standard deviation, while categorical variables were expressed as numbers and percentages. Comparison of continuous variables among groups was made using the Students t-test. Associations between two categorical variables were tested using the Likelihood ratio χ2 test, as appropriate. All tests of significance were two-tailed and p < 0.05 was considered statistically significant. Receiver operating characteristic (ROC) curve analysis was used to identify optimal cutoff value for GLS with maximum sensitivity and specificity for prediction of LV remodeling.
Results
A total of 100 patients with anterior STEMI were included in the study. They were classified according to admission plasma HbA1c level into two groups, chronic hyperglycemic group (patients with HbA1c ≥ 6.5%) (36 patients) and non-chronic hyperglycemic group (patients with HbA1c < 6.5%) (64 patients). Baseline demographics and clinical characteristics of study groups are shown in table 1.
Variables | Chronic hyperglycemia, (n = 36) | Non-chronic hyperglycemia, (n = 64) | p value |
---|---|---|---|
Age (mean ± SD) | 57.86 ± 8.05 | 53.82 ± 6.41 | 0.007 |
Gender | |||
Male | 32 (88.9%) | 40 (62.5%) | 0.03 |
Female | 4 (11.1%) | 24 (37.5%) | |
Hypertension | 32 (88.9%) | 36 (56.2%) | < 0.001 |
Diabetes | 32 (88.9%) | 2 (3.1%) | < 0.001 |
Dyslipidemia | 30 (83.3%) | 26 (40.6%) | < 0.001 |
Smoking | 25 (69.4%) | 8 (12.5%) | < 0.001 |
BMI (mean ± SD) | 29.08 ± 2.43 | 29.43 ± 2.93 | 0.12 |
SBP (mmHg) | 147.58 ± 14.3 | 118.68 ± 17.9 | < 0.001 |
DBP (mmHg) | 93.08 ± 10.21 | 75.82 ± 9.51 | < 0.001 |
Heart rate | 85.16 ± 6.94 | 89.12 ± 11.93 | 0.07 |
Killip class | |||
I | 23 (63.8%) | 42 (65.6%) | 0.17 |
II | 10 (27.7%) | 16 (25%) | 0.16 |
III | 3 (8%) | 6 (9%) | 0.11 |
All values are in mean ± SD, number, and percent %. BMI: body mass index, SBP: systolic blood pressure, DBP: diastolic blood pressure.
Laboratory investigation
Patients with chronic hyperglycemia had significantly higher levels of serum creatinine level (1.38 ± 0.37 vs. 0.83 ± 0.19 mg/dl, p < 0.001), random blood sugar (298.5 ± 82.5 vs. 138.5 ± 65.5 mg/dl, p < 0.001), and HbA1c (10.61 ± 1.89 vs. 5.58 ± 0.24%, p < 0.001). There was no significant difference between both groups as regard CKMB (157.36 ± 53.15 vs. 150.48 ± 33.69 u/l, p = 0.21) and troponin levels (6.19 ± 1.46 vs. 6.10 ± 1.62 ng/ml, p = 0.91).
Management of hyperglycemia
During hospital stay, all patients received rapid acting insulin subcutaneous injection. After discharge, patients with HbA1c ≤ 7.5% continue on oral hypoglycemic drugs and patients with HbA1c > 7.5% continue on long-acting insulin.
Echocardiographic parameters
There was no significant statistical difference between the two groups regarding baseline LVEDV (105.69 ± 9.16 vs. 99.92 ± 9.35 ml, p = 0.09), LVESV (56.31 ± 7.83 vs. 53.67 ± 6.59 ml, p = 0.07), and LVEF (43.47 ± 3.14 vs. 46.93 ± 4.62%, p = 0.08). GLS was significantly lower in patients with the chronic hyperglycemic group compared to the non-chronic hyperglycemic group (−13.52 ± 4.83 vs. −15.27 ± 1.87%, p = 0.009).
After 6 months, EDV and ESV were significantly increased in patients with chronic hyperglycemia (119.63 ± 14.24 vs. 105.69 ± 9.16 ml and 68.91 ± 13.59 vs. 56.31 ± 7.83 ml, p = 0.04 and 0.003, respectively). EF was significantly decreased in patients with chronic hyperglycemia (38.16 ± 4.94 vs. 43.47 ± 3.14%, p = 0.004). All echocardiographic parameters illustrated in table 2.
Variables | Chronic hyperglycemia (n = 36) | Non-chronic hyperglycemia (n = 64) | p-value | |
---|---|---|---|---|
EDV (ml) (baseline) | Mean ± SD | 105.69 ± 9.16 | 99.92 ± 9.35 | 0.09 |
EDV (ml) (follow-up) | Mean ± SD | 119.63 ± 14.24 | 105.14 ± 9.19 | 0.02 |
ESV (ml) (baseline) | Mean ± SD | 56.31 ± 7.83 | 53.67 ± 6.59 | 0.07 |
ESV (ml) (follow-up) | Mean ± SD | 68.91 ± 13.59 | 56.42 ± 6.95 | 0.003 |
EF (%) (baseline) | Mean ± SD | 43.47 ± 3.14 | 46.93 ± 4.62 | 0.08 |
EF (%) (follow-up) | Mean ± SD | 38.16 ± 4.94 | 47.18 ± 4.28 | < 0.001 |
E wave (cm/s) | Mean ± SD | 67.96 ± 21.45 | 43.20 ± 6.83 | < 0.001 |
A wave (cm/s) | Mean ± SD | 65.99 ± 29.44 | 95.15 ± 14.82 | < 0.001 |
E/A ratio | Mean ± SD | 1.31 ± 0.72 | 0.52 ± 0.21 | < 0.001 |
WMSI | Mean ± SD | 1.92 ± 0.56 | 1.29 ± 0.42 | 0.03 |
é wave (cm/s) | Mean ± SD | 5.85 ± 0.57 | 6.45 ± 0.75 | < 0.001 |
a` wave (cm/s) | Mean ± SD | 3.25 ± 0.57 | 3.85 ± 0.57 | < 0.001 |
E/é ratio | Mean ± SD | 11.66 ± 4.22 | 6.76 ± 1.61 | < 0.001 |
S wave (cm/s) | Mean ± SD | 7.29 ± 0.6 | 8.4 ± 0.91 | < 0.001 |
GLS (%) | Mean ± SD | −13.52 ± 4.83 | −15.27 ± 1.87 | 0.009 |
EDV: end-diastolic volume, ESV: end-systolic volume, EF: ejection fraction, WMSI: wall motion score index, GLS: global longitudinal strain.
In-hospital outcome
Heart failure and reinfarction were significantly higher in patients with chronic hyperglycemia (15 patients “45.5%” vs. 10 patients “16.7%” and six patients “18.2%” vs. two patients “3.3%,” respectively, p < 0.05). There was no statistical difference regarding arrhythmia, bleeding, and mortality (Table 3).
Six months outcome
Patients with chronic hyperglycemia had higher incidence of complications. Heart failure, LV remodeling, arrhythmias, and bleeding rates were significantly increased in patients with chronic hyperglycemia (13 patients “41.9%” vs. seven patients “12.1%”, 16 patients “51.6%” vs. eight patients “13.8%,” two patients “6.5%” vs. one patient “1.7%,” and two patients “6.5%” vs. one patient “1.7%,” respectively, p < 0.05) (Table 4).
Variables | Chronic hyperglycemia (n = 36) | Non-chronic hyperglycemia (n = 64) | p-value |
---|---|---|---|
Mortality | 2 (6.1%) | 2 (3.3%) | 0.09 |
Heart failure | 13 (41.9%) | 7 (12.1%) | 0.006 |
Reinfarction | 2 (6.5%) | 3 (5.2%) | 0.26 |
Arrhythmias | 2 (6.5%) | 1 (1.7%) | 0.02 |
Stroke | 1 (3.2%) | 0 (0%) | 0.08 |
Bleeding | 2 (6.5%0 | 1 (1.7%) | 0.02 |
LV remodeling | 16 (51.6%) | 8 (13.8%) | 0.005 |
ROC curve was used to assess the overall accuracy of GLS in predicting LV remodeling. Optimal cutoff value of GLS that predicts LV remodeling was ≥−13.5 – sensitivity: 100%, specificity: 93%, positive predictive value: 94%, negative predictive value: 100%, accuracy: 97%, and area under curve: 0.99.
Discussion
Hyperglycemia is associated with increased morbidity and mortality in patients with AMI. In the thrombolysis era, it has been reported that diabetes and chronic hyperglycemia as assessed by HbA1c level are prognostic factors for in-hospital mortality in patients with AMI8.
The purpose of the study was to evaluate the impact of chronic hyperglycemia on in-hospital and short-term outcome in patients with the first acute anterior MI treated with streptokinase as thrombolytic therapy.
The present study showed that hypertension, diabetes mellitus, smoking, and dyslipidemia were significantly more prevalent in the chronic hyperglycemic group.
These results are discordant with those reported by Fujino et al.9 who reported that there was no significant difference between patients with chronic hyperglycemia and patients without as regard hypertension and history of smoking (p = 0.065 and 0.736, respectively), while there was a significant difference between both patients groups as regard dyslipidemia (p = 0.031). This discrepancy might be attributed to larger sample volume included in their study.
The present study showed that serum creatinine was higher in patients with chronic hyperglycemia. This could be explained by the fact that diabetes mellitus is recognized as a leading cause of chronic kidney disease and end-stage renal failure.
In the present study, there was no significant difference regarding in-hospital mortality between the two groups (p = 0.14). Furthermore, Fujino et al.9 found no significant difference between chronic hyperglycemia and non-chronic hyperglycemia patients regarding in-hospital mortality (p = 0.79). Similarly, Chan et al.10 reported that elevated HbA1c levels were not associated with short-term cardiovascular outcome (all-cause mortality, cardiovascular mortality, rehospitalization for angina, and hospitalization for heart failure).
On the other hand, Timmer et al.11 observed that increasing levels of HbA1c were associated with increased mortality rates over an average 3.3 years of follow-up in 4176 consecutive STEMI patients submitted to PCI. This finding was partially related to the fact that increasing HbA1c levels were associated with adverse baseline characteristics such as a high cardiovascular risk profile.
After 6 months, there was no significant difference in mortality between both groups (p = 0.09). This was in agreement with Zaghla et al.12 who reported that HbA1c level was not found to be correlated with 6 months mortality.
Heart failure and LV remodeling were significantly increased in patients with chronic hyperglycemia. LV remodeling occurred in 51.6% versus 13.8% in the non-chronic hyperglycemia group, which was statistically significant. In the present study, patients with chronic hyperglycemia had lower level of GLS which can be used as a predictor of adverse myocardial changes, especially LV remodeling.
These findings consistent with the results by Mele et al.13 who found that patients with LV remodeling following AMI had lower GLS (−11.2 ± 2.5 vs. −14.8 ± 3.2, p = 0.003).
Conclusion
Chronic hyperglycemia patients had higher incidence of heart failure and LV remodeling following AMI. Speckle tracking can be used as a predictor of LV remodeling in this group of patients.
Study limitation
It was a single center study with relatively small number of patients and limited follow up period. Our study was applied on the first acute anterior MI patients only, excluding those with other types of acute coronary syndrome and previous MI. The reperfusion strategy was fibrinolytic therapy (streptokinase) and percutaneous coronary intervention (PCI) was not included.