CODEN (USA): IJPRIF, ISSN: 0974-4304, ISSN(Online): 2455-9563 Vol.11, No.02, pp 119-128, 2018
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Abstract : Background: Electrocardiogram (ECG) is a simple, non-invasive modality widely used for diagnostic and prognostic tools in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Early identification of three-vessel disease (3-VD) in ECG findings in NSTE-ACS with diabetes mellitus (DM) patients is important, due to consideration of prognosis and revascularization modalities. Previous studies that compare 3-VD incidence based on ST-segment-depression were not specified for NSTE-ACS with DM patients. Especially with our current national insurance system, it can be a guide for healthcare providers in terms of management strategies so that NSTE-ACS with DM patients get optimal management and revascularization. The objective of this study was to assess the predictive value of ST-segment depression for the incidence of 3-VD in NSTE-ACS with DM patients. Methods: 67 NSTE-ACS with DM patients that hospitalized from January 2015-December 2017 in Haji Adam Malik General Hospital were analyzed retrospectively. Patients were divided into two group based on ST-segment depression on admission ECG. Bivariate and multivariate analysis was performed to study the association between ST-segment depression and 3-VD, p-value < 0.05 was considered statistically significant. Results: Bivariate analysis shows that 3-VD incidence was higher in NSTE-ACS with DM patient accompanied by ST-segment depression compared to without ST-segment depression (80.6% vs 19.4 %, p <0.001). On multiple logistic regression analysis, patients with ST-segment depression had a
27.3 fold increased the risk for 3-VD compared to patients without ST-segment depression [OR 27.3 (6.117 – 121.851), p=0.000]. Conclusion: The presence of ST-segment depression on admission ECG in NSTE-ACS with DM patients was associated with a higher incidence of 3-VD and was the strongest independent predictor of 3-VD. In clinical practice, it may serve as a simple non-invasive tool for predicting 3-VD in NSTE-ACS with DM patients. Keywords : ST-segment Depression, NSTE-ACS, DM, 3-VD.
Acute Coronary Syndrome (ACS) is a main cardiovascular problem due to the high hospital admission and high mortality cases.1 Almost half of the cardiovascular death is caused by the acute myocardial infarction (AMI) (Departemen Kesehatan Republik Indonesia, 2008). IMA is a 30% cause of death in people with Diabetes Mellitus (DM).2 ACS is caused by disturbances of flow to coronary due to the atherosclerosis plaque as well as worsening of thrombus closing the lumen. A progression of plaque formation and a tearing of plaque can trigger a thrombus formation which progressing to the further coronary stenosis. DM is related to both of process, which are the plaque formation and intraluminal thrombus which causing infarction and worsened the cardiovascular condition.3 Some researchers are showing a diabetic pattern of CAD such as a significant number of stenosis, more spreading stenosis, and a multivessel.4,5 Factors on DM patient that can increase ACS risk are atherosclerosis acceleration, prothrombic state, and autonomic disfunction.6 While 20–30% of European patients with NSTE-ACS have known diabetes mellitus, a similar proportion may have undiagnosed diabetes or impaired glucose tolerance.7-10
Coronary angiography has an important role in ACS-NSTE intervention.11 Coronary angiography pattern on ACS-NSTE is various from normal to the worse and diffuse artery disease. Almost 20% of SKANEST patients found no epicardial lesions or non-obstructive epicardial lesions, and about 40-80% with 3VD.11 Multiessel diseases is a predictor of Major Acute Cardiovascular Event (MACE) on CAD patient after a long follow up monitoring.12 All patients with diabetes and complex multivessel disease should be discussed within a Heart Team. Overall, the threshold for CABG should be lower in patients with diabetes than in individuals without diabetes mellitus, and in low surgical risk patients with the multivessel CAD, CABG should
13,14,15
be favored over PCI, especially in the setting of complex disease.
Electrocardiogram (ECG) on admission can be an early marker of risk.16 Besides of a diagnostic need, ECG can also be used for assessing prognosis on patients with ischemic symptoms. ECG on admission can give
16,17,18
an important information and risk stratification on ACS.ECG findings of ST-segment depression can be a
16,18,19,20,21
strong predictor for a worse outcome.On substudy of FRISC II ECG can be found that an ST-segment depression on unstable angina pectoris patient is related to the increase of 100% 3-VD/Left main disease and this also can explain an increased risk of MACE.20 Other modalities such as echocardiography, nuclear scintigraphy, or computed tomographic coronary angiography may provide additional diagnostic and prognostic information, but it may not necessarily be available in health services and may take a long time.21
Predicting 3-VD is an important thing in relation to the care or referral of ACS-NSTE because not all center, especially on a referral hospital in Indonesia, have an angiography coronary facility or a Heart Team which consisted of the interventionist cardiologist, noninvasive cardiologist, cardiothoracic surgeon, and other multidisciplinary teams to make a decision. An especially on National Healthcare System by this day, this procedure can be made as a protocol and guideline so the ACS-NSTE with DM can have an optimal intervention or revascularization.
This was a single-center, retrospective cohort study on ACS-NSTE with DM patients on Haji Adam Malik General Hospital (HAM Hospital) Medan. The sampling method for this research is a nonprobability sampling, which is consecutive sampling. Observers were taking all the subjects with ACS-NSTE with DM until the minimal sample is reached. This study was held by data taking from the medical record from January 2015 to December 2017. Inclusion criteria are ACS-NSTE with DM who were hospitalized on HAM Hospital and undergone coronary angiography on admission without the history of valvular heart disease, congenital heart disease, cardiomyopathy or other cardiac disease and without history of taking digitalis medicine. Exclusion criteria are the ACS-NSTE with DM patients with bundle branch block, left ventricular hypertrophy, pacemaker rhythm and hypokalemia.
An observer was checking a medical record of the ACS-NSTE patient to see anamneses, physical examination, ECG, thorax x-ray and cardiac enzyme and other laboratory findings, and also coronary angiography. All these data would be collected systematically. From this data, the ECG findings will be divided into the two group. The first group is the ACS-NSTE with DM with ST-segment depression and the other group is the ACS-NSTE with DM without ST-segment depression on admission. From each group, the coronary angiography data were collected to assess the 3-VD. All data were analyzed the significancies by statistical
analysis to compare the 3-VD occurrence by ECG on ACS-NSTE with DM. CAD 3-VD would also be assessed as a predictor by a multivariate analysis.
Descriptive statistics was used to represent characteristics at the entry of the study. The data were assessed for normality of distribution and transformed as appropriate. Results were expressed as frequencies and percentages for categorical variables, mean, standard deviation (SD) for normally distributed variables and median for non-normally distributed variables. The normality test of numerical variables on all subjects using Shapiro Wilk. Chi-Square test were used to determine the categorical variable on ST-segment depression. Fisher exact dan Mann Whitney test was used to assessed bivariate and comparing means of the ST-segment depression based on 3-VD and non 3-VD. Significant variables on univariate analysis were further analyzed on multivariate analysis by logistic regression on the categorical variable and linear regression on numerical variable. Interobserver variability test was assessed using Kappa test. The clinical outcome was presented as frequency, percentage, odds ratio, and 95% confidence interval. The significant p-value was below 0.05
Total subjects of this study were 67 samples by the first group with ST-segment depression of 30 samples, and with the second group without ST-segment depression. Characteristics of research subjects can be seen in Table 1. From Table 1 can be seen the group with ST-segment depression has more cardiovascular risk factors such as hypertension, dyslipidemia, and CAD family history. Hypertension history was found in 27 samples (90%) in ST-segment depression group and 19 samples (51.4%) in without ST-segment depression group with a significant p-value of 0.001. Dyslipidmeia history was also higher in ST-segment depression group which was 12 samples (40%) and 6 samples (16.2%) in the group without ST-segment depression with a significant p-value of 0.029. CAD family history was also higher in ST-segment depression group which was 15 samples (50%) and 4 samples (10.8%) in the without ST-segment depression group, with a significant p-value of <0.001. No significant differences were found for smoking history in both groups. But it can be seen that more than half of both groups are smokers. On the physical examination were found that blood pressure and heart rate on admission were not significantly different.
Based on laboratory findings, there were significant differences on an increasing of troponin on both groups. On group with ST-segment depression, were found that higher troponin with mean 1.78 ± 3.93 as compare of 0.77 ± 1.64 on the group without ST-segment depression with the significant p-value of 0.018. Random blood glucose, fasting blood glucose and 2-hour postprandial were seen to be higher than normal but not significantly different on both groups. On both group were seen that HbA1C was higher from the standard for DM. HbA1C was seen higher on the group with ST-segment depression but not statistically significant. On the group with ST-segment depression, HbA1C was 8.6 ± 1.6, while 8.14 ± 1.93 on the group without ST-segment depression with the significant p-value of 0.313. Lipid profile finding was seen higher on the group with ST-segment depression but not statistically significant. There were no statistical significances on the lipid profile. On the group with ST-segment depression, creatinine was higher 1.37 ± 0.39 and 0.98 ± 0.28 on the group without ST-segment depression with the significant p-value < 0.001.
On echocardiography examination were seen the significant difference in the decreased left ventricular ejection fraction (LVEF). In group with ST-segment depression, LVEF <50% were 22 samples (73.3%) and LVEF >50% were 8 samples (26.7%). In Group without ST-segment depression, LVEF <50% were 12 (32.4%) samples and LVEF >50% were 25 (67.6%) with the significant p-value of 0.001. In ST-segment depression group were seen that ACS-NSTE with DM had a worse TIMI and GRACE score which describe more risk factors or other comorbidities in ST-segment depression group.
On Table 2 were seen that ECG was having a relationship with 3-VD on coronary angiography. 3-VD was found in 25 samples (80.6%) in ST-segment depression group and 6 samples (19.4%) in without ST-segment depression group. Meanwhile, non 3-VD was found over 5 (13.9%) samples in ST-segment depression group and 31 (86.1%) samples in without ST-segment depression group with OR (odds ratio) of 25.8 with the significant p-value <0.001.
Table 1. Sample Baseline Characteristic
Parameter | ST-segment Depression | Without ST- | |
---|---|---|---|
segment Depression | P | ||
(n=30) | (n=37) |
Sex (%) Male 20 (66.7) 29 (78.4) 0.282 10 (33.3) 8 (21.6)
Female
Age (years ± SD) 56.6 ± 6.3 57.57 ± 9. 0.662 Systolic BP (mmHg ± SD) 137 ± 20 130 ± 21 0.202 Heart rate 85.3 ± 21.37 84.3 ± 22 0.574
Hypertension (%) 27 (90) 19 (51.4) 0.001
Dyslipidemia (%) 12 (40) 6 (16.2) 0.029
Family history of CAD (%) 15 (50) 4 (10.8) < 0.001
Smoking (%) 18 (60) 21 (51.68) 0.789
Troponin 1.78 ± 3.93 0.74 ± 1.64 0.018 Random Blood Glucose 223 ± 100 263 ± 155 0.348 Fasting Blood Glucose 157.9 ± 59.7 143 ± 53.9 0.325 Two hour after meal Blood Glucose 212.8 ± 77.9 200.8 ± 67 0.504 HbA1C 8.6 ± 1.8 8.14 ± 1.93 0.313 Total Cholesterol 209.1 ± 73.69 194.6 ± 61.84 0.528 LDL 169 ± 43 132 ± 53 0.001 HDL 37.43 ± 11.73 43.5 ± 29.9 0.865 Trigliseride 151.8 ± 87.3 130.92 ± 50.28 0.504 Ureum 37.8 ± 18.2 44.77 ± 32.83 1 Creatinine 1.39 ± 0.4 1.08 ± 0.28 < 0.001 Hemoglobin 12.89 ± 1.9 13.02 ± 3.8 0.151
LVEF(%) ≥50 8 (26.7) 25 (67.6) 0.001 < 50 22 (73.3) 12 (42.4)
TIMI Score Moderate + High 26 (86.7) 22 (59.6) 0.014 Low 4 (13.3) 15 (40.5) GRACE Score Moderate + High 25 (83.3) 20 (54.1) 0.011 Low 5 (16.7) 17 (45.9)
Table 2. Association between ECG (With ST-segment Depression and Without ST-segment Depression) and The Incidence of 3-VD
Coronary Angiography OR p
ECG
Non
3-VD
With ST-segment Depression
Without ST-segment Depression
25.8 < 0.001
N25 5 (%) (80.6) (13.9)
N6 31 (%) (19.4) ( 86.1)
N 30 37 (%) (100) (100)
From the bivariate analysis based on 3-VD grouping from Table 3 were found that besides ST-segment depression, family history, troponin value, creatinine value, LVEF, TIMI score, GRACE score was having a relationship with the 3-VD incidence. On 3-VD group, CAD family history risk factor was found in 13 samples (41.9%) and on non 3-VD was 6 (16.7%) samples with p-value 0.022. Troponin value was also higher in the 3VD group which was 1.74 + 3.9 while on the non 3-VD group 0.27 + 1.7 with p-value 0.017. Creatinine value was also higher on 3-VD group with value was 1.27 + 3.6 mg/dL compare to non 3-VD group with value of
1.05 + 0.38 mg/dL with p-value 0.01. LVEF on the 3-VD group was seen to be lower. On 3-VD group were found that 22 (73.3%) sample had LVEF <50% while on non 3-VD with 12 (32.4%) samples with p-value
0.001. GRACE score and TIMI score were also higher on 3-VD. These described that other risk factors were also higher on 3-VD. Multivariate analysis on table 4 was also shown that ST-segment depression was the strongest predictor of 3-VD [OR 27.3 (6.117 – 121.851), p=0.000].
Table 3. Univariate Analysis of Factors Related to The 3-VD
3-VD | NON 3-VD | P | |
Parameter | |||
n = 31 | n = 36 |
Sex (%) Male 23 (74.2) 26 (72.2) 0.856 8 (25.8) 10 (27.8)
Female
Age (years ±SD) 57 ±6 57 ±9 0.874 Systolic BP (mmHg ± SD) 134 ± 19 132 ± 22 0.636 Heart rate 84 ± 21 85 ± 21 0.860
Hypertension (%) 24 (77.4) 22 (61.1) 0.151
Dyslipidemia (%) 10 (32.7) 8 (22.2) 0.355
Family history of CAD (%) 13 (41.9) 6 (16.7) 0.022
Smoking (%) 21 (67.7) 18 (50) 0.142 ECG
ST-segment Depression 25 (80.6) 5 (13.9) <0.001
Troponin 1.74 ± 3.85 0.74 ± 1.71 0.017
Random Blood Glucose 220 ± 98 266 ± 157 0.324
Fasting Blood Glucose 158 ± 60 143 ± 53 0.454
Two hour after meal Blood Glucose 200 ± 64 211 ± 78 0.674
HbA1C 8 ± 1.76 8.4 ± 1.9 0.485
Total Cholesterol 195 ± 72 205 ± 62 0.346
LDL 140 ± 54 137 ± 59 0.646
HDL 37 ±10 44 ±30 0.743
Trigliseride 140 ± 73 139 ± 67 0.706
Ureum 41.6 ± 24 41.8 ± 30.2 0.521
Creatinine 1.27 ± 0.36 1.05 ± 0.4 0.01
Hemoglobin 12.8 ± 1.4 13.5 ± 2.42 0.097
LVEF(%) ≥50 8 (26.7) 25 (67.6) 0.001 < 50 22 (73.3) 12 (32.4)
TIMI Score 26 (83.9) 22 (61.1) 0.039
Moderate + High 5 ( 16.1) 14 (38.9)
Low
GRACE Score Moderate + High 27 (87.1) 18 (50) 0.001 Low 4 (12.9) 18 (50)
Tabel 4. Multivariate Analysis on 3-VD on ACS-NSTE with DM
VARIABLES | P | OR | 95% C.I.for EXP(B) Lower Upper | ||
---|---|---|---|---|---|
STEP 1 | Hypertension CAD Family History Smoking ST-segment Depression Troponin Creatinin GRACE Score TIMI Score LVEF Constant | ,211 ,592 ,128 ,000 ,643 ,628 ,089 ,826 ,923 ,966 | ,291 ,587 3,479 71,621 1,092 ,552 5,324 1,233 ,922 ,857 | ,042 ,084 ,699 7,037 ,752 ,050 ,773 ,191 ,178 | 2,008 4,105 17,318 728,896 1,585 6,099 36,663 7,951 4,763 |
STEP 2 | Hypertension CAD Family History Smoking ST-segment Depression Troponin Creatinin GRACE Score TIMI Score Constant | ,212 ,563 ,122 ,000 ,645 ,622 ,082 ,809 ,963 | ,293 ,574 3,518 74,100 1,090 ,548 5,413 1,254 ,848 | ,043 ,087 ,716 8,032 ,754 ,050 ,809 ,201 | 2,012 3,781 17,292 683,659 1,577 5,984 36,210 7,834 |
STEP 3 | Hypertension CAD Family History Smoking ST-segment Depression Troponin Creatinin GRACE Score Constant | ,220 ,591 ,119 ,000 ,664 ,595 ,069 ,981 | ,304 ,605 3,547 75,610 1,083 ,526 5,663 ,919 | ,045 ,097 ,721 8,236 ,757 ,049 ,877 | 2,037 3,786 17,463 694,132 1,548 5,606 36,590 |
STEP 4 | Hypertension CAD Family History Smoking ST-segment Depression Creatinin GRACE Score Constant | ,221 ,667 ,113 ,000 ,566 ,061 ,986 | ,305 ,678 3,606 77,300 ,502 5,755 ,941 | ,046 ,115 ,740 8,254 ,048 ,920 | 2,039 3,995 17,582 723,928 5,297 35,995 |
STEP 5 | Hypertension Smoking ST-segment Depression Creatinin GRACE Score Constant | ,215 ,117 ,000 ,548 ,063 ,947 | ,302 3,540 68,247 ,483 5,624 ,790 | ,046 ,730 8,025 ,045 ,912 | 2,001 17,167 580,388 5,188 34,697 |
STEP 6 | Hypertension Smoking ST-segment Depression GRACE Score Constant | ,167 ,101 ,000 ,057 ,620 | ,270 3,710 51,065 5,726 ,235 | ,042 ,774 7,937 ,948 | 1,730 17,779 328,531 34,598 |
STEP 7 | Smoking ST-segment Depression GRACE Score Constant | ,070 ,000 ,030 ,000 | 3,978 27,301 5,597 ,026 | ,893 6,117 1,181 | 17,715 121,851 26,517 |
On this study, there were two groups of samples which were samples on the group with ST-segment depression and without ST-segment depression. ST-segment depression group had more risk factors such as CAD family history, hypertension, dyslipidemia, and higher creatinine. The previous study was also shown the similar results. Jin et al described that ST-segment depression group had more comorbidities and older than without ST-segment depression.22 FRISC II ECG study was as well shown that unstable angina pectoris on ECG with ST-segment depression was having more risk factors such as hypertension, older age, history of angina and infarction when compared to without ST-segment depression. On baseline characteristic table was shown that
ST-segment depression.22 FRISC II ECG study was as well shown that unstable angina pectoris on ECG with ST-segment depression was having more risk factors such as hypertension, older age, history of angina and infarction when compared to without ST-segment depression. On baseline characteristic table was shown that random blood glucose, fasting blood glucose and 2-hour post meal glucose and HbA1C were higher ST-segment depression group although it was not significantly differenced statistically. On those sample group, all those values were higher than normal limit value, showing that this population was suitable for uncontrolled DM. In ST-segment depression group, the HbA1C value was 8.6 ± 1.6 while in the group without ST-segment depression was 8.14 ± 1.93. This was similar to the previous study that on DM patients, plaque tearing was common. 23 DM was related to the worsening of plaque formation and intraluminal thrombosis that could cause infarction and cardiovascular deprivation.3 Troponin value was also seen to be higher in ST-segment depression group. troponin value was higher in with ST-segment depression group. On group with ST-segment depression were seen the increasing of troponin higher with the mean value of 1.78 ± 3.93 compared to the group without ST-segment depression which had mean value 0.74 ± 1.64 with significant p-value 0.018. This similar explanation was shown previous literature. The presence of ST-segment depression was needed worse ischaemic condition than normal ECG or inversion of T wave.24 If the ischaemic were worse, the myocardial necrosis would have happened (myocardial infarction).25 These findings were similar to the study held
22,26
previously by Kaul et al on 2003 and Jin et al on 2016.Creatinine was also seen to be higher in ST-segment depression group. This probably was caused by the other risk factors on the group with ST-segment depression such as hypertension and the more reduced LVEF. More samples on ST-segment depression group were also seen to had LVEF <50% which was on 22 samples (73.3%) while on the group without ST-segment depression of 12 samples (32.4%) with significant p-value 0.001. These findings were also supported by the previous study held by Ghaffari in 2010 that described that ACS-NSTE with ST-segment depression had a more decreased LVEF. On group with ST-segment depression, LVEF found were 42.35 ± 9.47% while in without ST-segment depression group had a mean value of 50.42 ± 8% with the significant p-value of 0.001.21 A lower LVEF in ST-segment depression group could be caused by an ischemic condition which worsens and also the involvement more coronary artery. Hypertension and decreasing LVEF were also explained in the previous
27,28
study which can cause a deprivation of renal function.The assessment of risk stratification such as TIMI and GRACE score was higher in ST-segment depression group. This probably was caused by the more risk factor in ST-segment depression group besides the ST-segment depression which already added a score on this stratification.
This study was shown the significant incidence 3-VD between ST-segment depression group and without ST-segment depression group with OR 25.8 with the significant p-value 0.001. This study was also supported by the previous study. The 3-VD incidence on STEMI was significant (>50%) and could be up to
29 30,31,32
80%.Similar prevalence also happened on ACS-NSTE.Almost half of the patients were proved to had a significant multivessel stenosis.33 On study held by Diderholm showed that the ST-segment depression on unstable angina pectoris patients was related to the increasing 100% on 3-VD incidence.20 The study held by Jin et all on 2016 was shown the higher occurrence of 3-VD in ST-segment depression group which was 53.5%.22 Ghaffari et all in 2010 were shown that ACS-NSTE with ST-segment depression had 58.3% 3-VD occurrence if compare to without ST-segment depression group.21 In this study, 3-VD on group with ST-segment depression was 24 samples (80.6%) while on the group without ST-segment depression was 6 samples (19.54%). This value was relatively higher than the previous study by Morgan 2004 than shown the diabetic pattern of the CAD with the significant stenosis, more spreading disease and the multivessel involvement.4 Some studies were
34,35,36,37,38
shown that DM patient had multivessel incidence which was higher.On angiography result or
39,40
autopsy, a patient with diabetes had 2-VD or 3-VD incidence higher than the non-DM patient.On one big autopsy study were found that adult diabetecian had 83% chances of 2-VD or 3-VD.41
This result was shown that on ACS-NSTE with DM who had ST-segment depression on ECG had a 3VD incidence higher than without ST-segment depression. Multivariate analysis was shown that ST-segment depression was the strongest predictor of 3-VD (OR 27.3 (6.117 – 121.851), p=0.000]. This also was supported by the previous study by Misumida, et al in 2015. ST-segment depression was found to be the strongest predictor of LM and or 3-VD on an ACS-NSTE patient with relative risk of 2.98 with the significant p-value of
0.001.42
Based on the results of data analysis obtained in this study can be concluded that the presence of ST-segment depression on admission ECG in NSTE-ACS with DM patients was associated with a higher incidence of 3-VD and was the strongest independent predictor of 3-VD.
Conflict of interest: None declared. Richard M.Jacoby , Richard W.Nesto ,
359 : 2140–2144
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