Silent Myocardial Ischemia ( SMI ) and its Association with Microalbuminuria in Type 2 Diabetes Mellitus ( DM )

Background: As silent myocardial ischemia (SMI) is more common in diabetic population leading to the development of future coronary artery disease (CAD), so its early diagnosis is important. SMI can be diagnosed by conventional cardiac stress testing. Presence of SMI can also be suspected by microalbuminuria (MAU) because recently it is claimed that MAU is one of the important predictor for cardiovascular disease. Objective: The study was designed to explore the association between SMI & MAU in type 2 DM. Methods: It was a cross sectional study carried out in the Department of Biochemistry, BSMMU during the period of July 2006 to June 2008. One hundred diagnosed type 2 DM patients were selected from out patient department of BIRDEM. Enrolled study subjects were advised to do ETT and then categorized as ETT +ve & ETT-ve on the basis of ETT findings. Urinary micro albumin was measured in all study subjects. Unpaired t test, , chi square test, odds ratio were used to see the level of significance Results: Among the 100 type 2 diabetic subjects of both sexes 50 (male -24, female26) were ETT +ve designated as type 2 DM with silent MI and rest 50 ( male25 , female-25) were ETT –ve designated as type 2 DM without silent MI. 21 patients (42%) out of 50 type 2 DM with silent MI & 16 patients (32%) out of 50 type 2 DM without silent MI found to have microalbuminuria. Calculated odds ratio was 1.5. Conclusion: Microalbuminuria is a possible risk factor for SMI in type 2 DM. Urinary micro albumin can be used particularly as a screening test for early detection of SMI. Key word: SMI (Silent myocardial ischemia), MAU (Microalbuminuria), Type 2 DM. [BSMMU J 2012; 5(1):42-45] (chest pain) events. Silent myocardial ischemia (SMI) is characterized by lack of final clinical event.3 Silent myocardial ischemia is particularly concerned in diabetic patients. It is suspected that partial or complete autonomic denervation in diabetic causes impaired symptom perception e.g. lack of recognition of chest pain leading to SMI.4 Silent myocardial ischemia (SMI) can be detected by using cardiac stress testing. SMI has been defined as exercise induced ST depression of >1mm in the absence of CAD symptoms5. Patients with a resting ECG suggestive of ischemia or infarction should undergo stress testing independent of previous or ongoing symptoms. In addition, asymptomatic patients with diabetes and two or more cardiovascular risk factors should also undergo stress testing. These risk factors include: total cholesterol >240mg/dl, LDL>160mg/dl, HDL<35mg/dl, BP>140/90mm Hg, smoking, family history of premature CAD and microalbuminuria or proteinuria.4 Microalbminuria in type 2 DM reflects an underlying predisposition to developing progressive kidney diseases as well as serving as a marker of predilection for generalized Address for Correspondence: Dr. Shahana Zabeen, Assistant Professor, Department of Biochemistry, Anwer Khan Modern Medical College, Dhaka, Bangladesh. cardiovascular disease.6 Persistent microalbuminuria has also been associated with an increase risk of atherosclerosis and cardiovascular mortality. Therefore, patients with diabetes should be screened regularly for microalbuminuria.7 Silent myocardial ischemia leading to development of future CAD is common in Type 2 DM but more common in Type 2 DM with microalbuminuria. Therefore, microalbuminuria can be used as an early marker as well as for risk stratification of cardiovascular disease.8 Microalbuminuria is defined as low level of urinary albumin excretion of 30 to 300 mg/day or 20-200 μg/min in which it gives the urinary concentration of albumin 20-200mg/dl.9,11 The possible pathophysiologic link between microalbuminuria and atherosclerosis is the increased generalized transvascular leakage of albumin. It is hypothesized that the systemic transvascular leakiness may also include lipoproteins, thus allowing for increased lipid penetration into the vessel wall. The leakiness might be due to hemodynamic factors or structural or functional perturbations of the endothelium or the intracellular matrix beneath.10 Coronary artery disease (CAD) is the most common form of heart disease and the single most important cause of premature death in all regions of the world. Since the silent myocardial ischemia (SMI) is more common in diabetic population therefore identification of SMI in many asymptomatic type 2 diabetic patients are important for the prevention of future myocardial infarction. SMI is diagnosed by conventional cardiac stress testing. Presence of SMI can also be suspected by microalbuminuria (MAU) because recently it is claimed that as an early marker microalbumin, may be a useful indicator for early detection of SMI particularly for screening purpose.

Silent myocardial ischemia is particularly concerned in diabetic patients.It is suspected that partial or complete autonomic denervation in diabetic causes impaired symptom perception e.g.lack of recognition of chest pain leading to SMI. 4 Silent myocardial ischemia (SMI) can be detected by using cardiac stress testing.SMI has been defined as exercise induced ST depression of >1mm in the absence of CAD symptoms 5 .Patients with a resting ECG suggestive of ischemia or infarction should undergo stress testing independent of previous or ongoing symptoms.In addition, asymptomatic patients with diabetes and two or more cardiovascular risk factors should also undergo stress testing.These risk factors include: total cholesterol >240mg/dl, LDL>160mg/dl, HDL<35mg/dl, BP>140/90mm Hg, smoking, family history of premature CAD and microalbuminuria or proteinuria. 4croalbminuria in type 2 DM reflects an underlying predisposition to developing progressive kidney diseases as well as serving as a marker of predilection for generalized cardiovascular disease. 6Persistent microalbuminuria has also been associated with an increase risk of atherosclerosis and cardiovascular mortality.Therefore, patients with diabetes should be screened regularly for microalbuminuria. 7Silent myocardial ischemia leading to development of future CAD is common in Type 2 DM but more common in Type 2 DM with microalbuminuria.Therefore, microalbuminuria can be used as an early marker as well as for risk stratification of cardiovascular disease. 8croalbuminuria is defined as low level of urinary albumin excretion of 30 to 300 mg/day or 20-200 µg/min in which it gives the urinary concentration of albumin 20-200mg/dl. 9,11he possible pathophysiologic link between microalbuminuria and atherosclerosis is the increased generalized transvascular leakage of albumin.It is hypothesized that the systemic transvascular leakiness may also include lipoproteins, thus allowing for increased lipid penetration into the vessel wall.The leakiness might be due to hemodynamic factors or structural or functional perturbations of the endothelium or the intracellular matrix beneath. 10ronary artery disease (CAD) is the most common form of heart disease and the single most important cause of premature death in all regions of the world.Since the silent myocardial ischemia (SMI) is more common in diabetic population therefore identification of SMI in many asymptomatic type 2 diabetic patients are important for the prevention of future myocardial infarction.SMI is diagnosed by conventional cardiac stress testing.Presence of SMI can also be suspected by microalbuminuria (MAU) because recently it is claimed that as an early marker microalbumin, may be a useful indicator for early detection of SMI particularly for screening purpose.

Methods:
It was a cross sectional study carried out in the Department of Biochemistry, BSMMU during the period of July 2006 to June 2008.Diagnosed type 2 DM patients were selected from out patient department of BIRDEM.
Enrolled study subjects were advised to do ETT and fifty subjects were selected randomly as ETT +ve (with silent myocardial ischemia) & fifty as ETT -ve (without silent myocardial ischemia) on the basis of ETT findings.Exercise ECG (ECG during ETT) was performed by using 12 standard leads on a treadmill according to Bruce protocol.The protocol had seven stages, each lasting 3 min resulting in 21 minute exercise for a complete test 12 .
The exercise test was considered positive if there was a horizontal and down slopping ST segment depression of at least 1 mm occurring at least 0.08s after the J point.The test was considered negative when the heart reached the maximal predicted exercise heart rate (calculated without a change in ST segment with the ASTRAND formula, 220age) without a change in ST segment 12 .
For micro albumin desired amount of urine was collected from ETT +ve & ETT-ve patients.Urinary micro albumin concentration was measured by immunometric assay 9 .Microalbuminuria is defined as urinary albumin excretion of 30 to 300 mg/day or 20-200 µg/min.Chi square test, unpaired t test and odds ratio were used to see the level of significance.

Results:
Table I

Discussion:
Cardiovascular disease is the leading cause of death among people with diabetes mellitus.Silent myocardial ischemia (SMI) is particularly concerned in diabetic patients.Recently many studies have identified microalbuminuria (MAU) as a possible risk factor for cardiovascular morbidity and mortality in people with diabetes besides other conventional risk factors such as hypertension ,dyslipidaemia and smoking. 5,13Diabetic patients with MAU have 8-15 times higher cardiac mortality than diabetic patients without MAU.A recent meta-analysis revealed that, in people with diabetes, MAU is associated with an odds ratio of an 2.1 for cardiovascular mortality 14 .
Patients with SMI have more frequent adverse cardiac events than patients without SMI.
In this cross sectional study our attempt was to demonstrate an association between SMI & MAU.Our study has revealed MAU as a possible risk factor for SMI in type 2 DM with OR of 1.
shows grouping of the study subjects with age & sex distribution.Unpaired t test & Chi square test done but no significant differences found between two groups with respect to age & sex.In table III microalbuminuria was evaluated as a risk factor to develop SMI in type 2 DM .Twenty one (42%) patients out of 50 type 2 DM with silent MI & sixteen (32%) patients out of 50 type 2 DM without silent MI found to show microalbuminuria .Calculated odds ratio was 1.5.
19 Almost similar findings were observed in the study ofCorona et al. 200515(OR 1.90),Muthu et al. 200816(OR 1.38), Yuyun et al. 2004 10 (OR 1.40), Lowry, 2007 17 (OR 1.96), & Weir, 2007 18 (OR 1.43).This appears to be permissive to our findings that MAU is associated with SMI .In EPIC -NORFOLK study(1993- 2002)researchers investigated the prognostic significance of albuminuria with baseline CHD events.They found MAU to be associated with total mortality with OR 1.61.Another study demonstrated a significant association between MAU & SMI in a cohort of 1576 Native Americans with diabetes.Later the LIFE study confirmed that the CAD risk associated with other conventional risk factors becomes more than doubled in the presence of MAU18.However it is also becoming increasingly recognized as an independent risk factor for cardiovascular disease in patients with or without diabetes.The recent stenostudy has demonstrated that multifactorial interventions can significantly reduce cardiovascular events in microalbuminuric patients with type 2 diabetes.19Conclusions:SMI can be suspected by the presence of MAU in type 2 DM.Therefore MAU can be used particularly as a screening test for early detection of SMI.Early detection of SMI in type 2 DM can prevent future CAD which is the most frequent cause of death in type 2 diabetic patients.