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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 7  |  Issue : 3  |  Page : 207-211

Prevalence of asymptomatic silent myocardial ischemia among type 2 diabetes mellitus patients in Bangalore - A hospital-based cross-sectional study


Department of General Medicine, M. S. Ramaiah Medical College, Bengaluru, Karnataka, India

Date of Submission17-May-2021
Date of Decision12-Aug-2021
Date of Acceptance17-Oct-2021
Date of Web Publication14-Dec-2021

Correspondence Address:
Nagappa H Handargal
M. S. Ramaiah Medical College, Bengaluru - 560 054, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jpcs.jpcs_33_21

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  Abstract 


Background: Earlier diagnosis of asymptomatic coronary artery disease (CAD) in diabetics may prevent catastrophic cardiac events and hence warrants the need for detection of silent myocardial ischemia (SMI). Therefore, the study aimed to assess the role of treadmill test (TMT) in patients who were asymptomatic, to detect and estimate the occurrence of SMI (positive exercise TMT), and to find the association between presence of SMI and duration of diabetes mellitus (DM). Methodology: A cross-sectional study was undertaken among 162 DM cases (type 2) with a mean age of 55.32 ± 11.89 years, who had undergone a TMT without any CAD evidence clinically. All the subjects had normal 12 lead electrocardiography and underwent TMT. Results: Among 162 subjects, TMT was positive in 63 (38.9%) study subjects. TMT positivity for inducible ischemia in type 2 DM patients was associated with increasing age, higher body mass index (BMI), smoking, higher HbA1C, albuminuria, retinopathy, and atherosclerotic cardiovascular disease (ASCVD) risk score. Smoking, diabetic retinopathy, and urine albumin were associated with TMT significantly (P value < 0.005). A significant linear increasing trend in proportion of TMT positive over HbA1c was observed. Mean height of TMT-positive subjects (159.2 ± 7.47 cm) was more than TMT-negative subjects (P < 0.005). The mean BMI (29.69 ± 3.58 kg/m2) and triglycerides (173.87 ± 112.7 mg/dl) of TMT-positive subjects were more than TMT-negative subjects (P < 0.005). Conclusion: CAD prevalence is greater in asymptomatic cases of type 2 DM in this geographic region. A significant linear increasing trend was observed in TMT positive over HbA1c. Hence, TMT can be incorporated in routine screening for SMI in patients suffering from diabetes.

Keywords: Coronary artery disease, diabetes mellitus type 2, electrocardiography, myocardial ischemia


How to cite this article:
Handargal NH, Shetty SJ. Prevalence of asymptomatic silent myocardial ischemia among type 2 diabetes mellitus patients in Bangalore - A hospital-based cross-sectional study. J Pract Cardiovasc Sci 2021;7:207-11

How to cite this URL:
Handargal NH, Shetty SJ. Prevalence of asymptomatic silent myocardial ischemia among type 2 diabetes mellitus patients in Bangalore - A hospital-based cross-sectional study. J Pract Cardiovasc Sci [serial online] 2021 [cited 2022 Jun 28];7:207-11. Available from: https://www.j-pcs.org/text.asp?2021/7/3/207/332488




  Introduction Top


Diabetes is a common chronic noncommunicable disease affecting both the developing and developed countries of the world. Diabetes mellitus (DM) simply refers to a group of common metabolic disorders which shares the phenotype of hyperglycemia.[1] It is caused due to defect in insulin secretion and/or insulin action resulting in hyperglycemia with disturbances of carbohydrate, protein, and fat metabolism.[2] The International Diabetes Federation (IDF) estimates that globally around 415 million suffer from diabetes, and out of these, 91% are the ones having DM type 2 (T2DM).[3],[4] With this, diabetes conquers about 8.8% of the world's population and IDF predicts that diabetes cases will exponentially rise to around 642 million by 2040.[3],[4] India occupies among the “top three” countries (India, China, and U. S.), and has the estimation of highest number of diabetes cases, which is the same as identified for 1995.[5]

A major reason for deaths in 70%–80% of diabetes patients is coronary artery disease (CAD).[6] CAD is progressive in diabetic patients, and usually remains asymptomatic turning out to be the undiagnosed part of a clinical iceberg. DM is an independent and modifiable risk factor in the development of coronary heart disease (CHD). The mortality related to cardiac diseases is doubled in case of diabetic men and quadrupled in case of diabetic women versus their nondiabetic counterparts.[7] CAD risks are greater for those with DM type 2, and with a past medical history of myocardial infarction.[8],[9],[10]

Thus, the hidden cardiovascular disease (CVD) risk in diabetes can only be deliberated by a routine screening program or the silent myocardial damage can engulf major mortality proportions in diabetes considering the transition in lifestyle and diet.[11] Routine screening of DM type 2 for asymptomatic CAD with electrocardiography (ECG) remains controversial, as majority of them present with normal ECG.[12] The American Diabetes Association (ADA) recommends that a treadmill exercise test (TMT) or a coronary artery angiography to be performed in DM patients if they have additional CVD risk factors.[13] This is because silent myocardial infarction is well known in case of asymptomatic T2DM patients with normal ECG. Thus, TMT has been used as a screening test to detect asymptomatic CAD which may cause sudden MI and death if undetected. TMT is thus used as one of the best detection methods which is done before subjecting patients to highly invasive coronary angiography (CAG). The significance of exercise electrocardiograph can be understood from the fact that it can identify the majority of patients likely to have ischemia during their day-to-day activities, and is the most important screening test for detection of CAD.[14]

Silent myocardial ischemia (SMI) is common in cases of diabetes and may delay or mask the CAD diagnosis, particularly in its early stages.[15] CAD is a microvascular complication accounting for as many as 80% of deaths in diabetic patients; furthermore, the SMI prevalence among the individuals with DM is high ranging from 20% to >50%.[16] The screening for early myocardial ischemia helps in preventing worsening of the cardiac disease, especially in high-risk groups who had a family history of CVDs. The study aimed to assess the role of TMT in asymptomatic cases of diabetes to detect SMI, to evaluate the prevalence of SMI in diabetics, and evaluate the association between the diabetes duration and TMT results, in turn emphasizing the need for TMT in asymptomatic cases suffering from diabetes from long time. The study also proposed to recognize the relation of other risk factors in developing SMI among the populace of Bangalore.


  Methodology Top


A cross-sectional study was undertaken among adult study subjects who attended Medicine and Cardiology outpatient department in a tertiary care center in Bengaluru, Karnataka. The ethical approval was obtained from the institutional research and ethics committee. Written informed consent was obtained from the study subjects prior to the commencement of the study.

Based on a previous study, it was found that SMI prevalence was 37.3% in T2DM patients.[4] Expecting similar findings in the study, considering relative precision of 20% and desired confidence of 97%, the required sample size is estimated to be 162 study subjects.

The study subjects with type 2 DM patients diagnosed by American Diabetes Association criteria (fasting blood sugar [FBS] ≥126 mg/dL, postprandial blood sugar (PPBS) ≥200 mg/dL, and glycated hemoglobin A1c ≥6.5%) who have undergone an exercise TMT were included in the study.[17] The study subjects with manifestations such as pregnancy, angina pectoris, acute coronary syndrome, left bundle branch block, unstable rhythm, severe valvular heart disease, any cardiomyopathy, uncontrolled heart failure, severe hypertension (>200/110 mmHg), and history of myocardial infarction, CVD, or coronary revascularization were excluded from the study.

The study subjects were interviewed through a structured proforma comprising demographic details such as name, age, sex, personal, occupational, and medical history. The history of presenting complaints on cardiac symptom analysis and history on details about T2DM duration with treatment history were recorded. Physical examination with a cardiovascular evaluation and assessment of peripheral pulses was also performed. Blood pressure was noted in both the postures (i.e., supine and standing postures). Body mass index (BMI) was measured, and was calculated by Quetelet's formula, and patients were accordingly categorized. Resting echocardiography, FBS and PPBS, glycosylated hemoglobin, lipid profile, blood urea, serum creatinine, urine albumin, and fundoscopy were carried out for all the study subjects. Other relevant investigations which were assessed on a case-by-case basis as recommended by the treating physician were also conducted.

All the patients had normal 12-lead electrocardiogram and underwent a treadmill exercise test. Following a standard 12 lead electrocardiogram, a torso ECG was obtained in the supine position and in the sitting or standing position. Blood pressure was noted in both the positions and the patient was instructed on how to perform the test. TMT was conducted among the patients by refraining food and caffeinated beverages 3 h prior to testing. The subjects were also advised to wear comfortable shoes and loose-fitting clothes. Standard multistage maximal exercise test was done on a motorized treadmill according to Bruce protocol.[18] The heart rate, electrocardiograms, and blood pressure were recorded on completion of each exercise stage, immediately before and after stopping the exercise and for each minute for at least 5–10 min in the recovery phase. Exercise test was stopped in patients on following the achievement of target heart rate or on any abnormal ischemic response or on fatigue, or dyspnea. This was defined as development of 0. 10 mV (1 mm) of J point depression which is measured from the PQ junction, along with an almost flat ST segment slope (< l mV/s), and also with a depression after the J point (≥0.10 mV 60–80 ms), in three consecutive beats along with a stable baseline.

Statistical analysis

Descriptive analysis of the data was assessed using R i386 3.6.3. Continuous variables were represented by mean ± standard deviation form. Categorical variables were represented as frequency tables. Categorical variables were compared using Chi-square test. Trend analysis was assessed using Cochran–Armitage trend test, continuous data were compared using t-test/welch t-test/Mann–Whitney U-test. P <0.05 was considered as significant.


  Results Top


Overall, 162 subjects of mean age 55.32 ± 11.89 (in years) were considered. [Table 1] depicts that the mean age of TMT-positive subjects was more than TMT-negative subjects (P = 0.0041). Using Cochran–Armitage trend test, a significant linear increasing trend in the TMT positive proportion was noted, over timespan of diabetes. A significant association (P < 0.05) was noted for TMT scores with smoking history, incidence of diabetic retinopathy and levels of urine albumin. A linear increasing trend was observed for TMT positive cases with sero-positivity of HbA1c. The mean height of TMT-positive subjects (159.2 ± 7.47 cm) was greater than TMT-negative subjects (156.97 ± 5.84) with P value < 0.005. The mean BMI (BMI, 29.69 ± 3.58 kg/m2) and triglycerides (173.87 ± 112.7 kg/m2) of TMT-positive subjects were greater than TMT-negative subjects with P value 0.0060. The mean FBS (194.54 ± 79.58 mg/dl), PPBS (243.02 ± 89.17 mg/dl), and atherosclerotic CVD risk score (0.2 ± 0.16) were greater in TMT-positive subjects with P value < 0.001. Using one-tailed Welch t-test, it was concluded that mean of creatinine (1.05 ± 0.36 mg/dl) was greater in TMT-positive subjects with P = 0.0045.
Table 1: Comparison of different factors between treadmill test-positive and negative subjects

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[Figure 1] depicts that 63 TMT-positive patients had undergone CAG and 58 had CAD significantly. In 27 of them, triple-vessel disease was found, while 21 had double-vessel disease. Forty-eight patients were successfully treated by graft technique (i.e., coronary artery bypass grafting). Out of 162 patients, TMT was positive in 63 (38.9%) and was negative in 99 patients (61.1%). Hence, the SMI prevalence was 38.9%.
Figure 1: The distribution of study population based on TMT positivity

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[Table 2] depicts that among 63 patients who underwent TMT, CAG showed significant atherosclerosis among 58 patients and 5 patients were not having any significant CVD. CAG has been done to know the extent of coronary vessels involved as well as the site of obstruction so that it will help in better management of CAD due to early detection. TMT was false positive in 5 patients. The positive predictive value (PPV) of TMT was 96.02% and the negative predictive value (NPV) was 100%. Sensitivity was 100% and specificity was 95.19%. Higher sensitivity and specificity signify that proportion of patients with which TMT was useful in early detection of CAD in T2DM patients as compared to coronary angiogram which is the gold standard are very high.
Table 2: Sensitivity analysis of treadmill test

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  Discussion Top


CAD is multifactorial in etiology and has several important risk factors, and one of the important modifiable risk factors is diabetes. Early detection of asymptomatic CAD in T2DM may prevent catastrophic cardiac events. Therefore, sophisticated cardiovascular noninvasive tests should be proposed for earlier recognition of CAD in diabetes patients. Exercise electrocardiograph can identify the patients likely to have significant ischemia during their daily activities and remain the main screening test for significant CAD. The study aimed to evaluate SMI in diabetic patients (without any symptoms of ischemia) by exercise treadmill test.

Among 162 diabetic patients without any prior indication of CAD, TMT was positive in 63 (38.9%) and was negative in 99 patients (61.1%). The results were in line with the prevalence recorded by Swaminathan and Gayathri and Hussain which showed that TMT was positive in 30% and 36.5% of the type 2 DM cases, respectively.[19],[11]

A statistically significant difference was found between mean diabetes duration and TMT documented SMI (P < 0.001). Another research by Langer A et al. showed that as a diabetes duration increased, chances of TMT documented silent MI increased.[20] Another study by Kyoung Kim et al. recommended CAD screening by TMT among the elderly geriatric population in whom diabetes duration was >10 years.[21] They found that the major distinction between the patients without symptoms having coronary stenosis and those with negative ETT is the diabetes duration and age. PPV of ETT was 48% in predicting CHD, and the value was higher in the elderly patients (≥60 years), long duration of diabetes (≥10 years) and in those having cardiac symptoms. To reduce cost toward health care, screening for CAD in whom symptoms were not present could be restricted to elderly patients with diabetes 10 years or more.[21]

The increased levels of glycosylated hemoglobin indicate poor control of sugar and can have an impact on heart diseases. Therefore, a statistically significant difference (P = 0.0028) was found in HbA1C (%) levels and the treadmill exercise results groups which is similar to a study done by Swaminathan and Gayathri (P < 0.001).[19] Valensi et al. stated that an increase in HbA1c levels was associated with a proportional growth in the coronary vessels' involvement associated with arterial disease (P<0.0001).[22]

In TMT-positive group versus the TMT-negative group, serum triglyceride, VLDL, and HDL levels were greater in the TMT-positive group (P = 0.0045). Similar results were documented by Swaminathan and Gayathri in their study where serum triglyceride levels were 176.6 mm/dL and cholesterol was 174.4 mm/dL.[19] This was also in line with the study done by DeLuca et al. which found that dyslipidemia was common among the individuals with T2DM, and majority of the abnormality was elevated serum triglyceride levels (73.3%).[23] Lehto et al. found among 1059 subjects had a twice-fold increase in the risk of CHD, in whom a high level of cholesterol level (serum) was seen.[24] Another case–control study was conducted by Panagiotakos et al. on 272 patients and found that the LDL/HDL ratio was an important factor of heart diseases in DM patients. The study also quoted that LDL-to-HDL cholesterol ratio was more than 8 and was related to a 66% rise in the risk of developing CAD.[25]

The PPV of TMT was 96.02% and the NPV was 100%. Sensitivity was found to be 100% and specificity was found to be 95.19%. This contrasts with a study of 147 subjects where the mean specificity and sensitivity of exercise testing were reported as 77% and 68%, respectively.[26]

Among the 63 participants who undergone TMT, CAG showed significant CVD among 58 patients and 5 patients were not having any significant CVD. Goraya et al. showed that three-fourth of individuals with DM had ischemic heart disease, and IHD >50% of asymptomatic subjects had multivessel disease. Hence, DM can be a “CHD equivalent”.[27] Undoubtedly, CAG is a reliable and accurate tool in ischemia detection. However, TMT is also an equally effective screening method for the diagnosis of CAD in asymptomatic T2DM patients in region where angiography is unavailable. However, a lot more research is expected in this regard.

The study has a major positive impact since it focused on various risk factors of CVDs such as alcohol, family history of premature CAD or retinopathy, or any smoking history which were available. The study was limited since it used a retrospective design which is a driving factor for selection bias, and focused on a small population; hence, further studies are recommended on a large scale study population in the near future.


  Conclusion Top


The SMI was highly prevalent in T2DM patients. It depicts longer the diabetes duration, greater chances of having SMI. Therefore, as a health-care professional, a step toward early screening of T2DM patients can prevent many untoward cardiac events.

Ethics clearance

The ethical approval was obtained from the institutional research and ethics committee, Ramaiah Medical College, [Reference number: SS-1/EC/02/2017] Bangalore, India.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J. Harrison's Principles of Internal Medicine. 19th ed. New York. NY, USA: McGraw Hill Education; 2015. p. 2399.  Back to cited text no. 1
    
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Yoo WS, Kim HJ, Kim D, Lee MY, Chung HK. Early detection of asymptomatic coronary artery disease in patients with type 2 diabetes mellitus. Korean J Intern Med 2009;24:183-9.  Back to cited text no. 5
    
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Khanapure SP, Parmar D, Bajaj G, Mural RH. Prevalence of silent coronary artery disease (CAD) in asymptomatic T2DM – A prospective study. Int J Contemp Med Res 2017;4:2341-5.  Back to cited text no. 10
    
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Valensi P, Sachs RN, Harfouche B, Lormeau B, Paries J, Cosson E, et al. Predictive value of cardiac autonomic neuropathy in diabetic patients with or without silent myocardial ischemia. Diabetes Care 2001;24:339-43.  Back to cited text no. 22
    
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Deluca AJ, Saulle LN, Aronow WS, Ravipathi G, Weis MB. Association of hemoglobin A1c with prevalence of silent myocardial ischaemia. Am J Cardiol 2005;95:1472-4.  Back to cited text no. 23
    
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Gianrossi R, Detrano R, Mulvihill D, Lehmann K, Dubach P, Colombo A, et al. Exercise-induced ST depression in the diagnosis of coronary artery disease. A meta-analysis. Circulation 1989;80:87-98.  Back to cited text no. 26
    
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Goraya TY, Leibson CL, Palumbo PJ, Weston SA, Killian JM, Pfeifer EA, et al. Coronary atherosclerosis in diabetes mellitus: A population-based autopsy study. J Am Coll Cardiol 2002;40:946-53.  Back to cited text no. 27
    


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