Coronary Artery Disease
Silent myocardial ischemia and microalbuminuria in asymptomatic subjects with non–insulin-dependent diabetes mellitus☆

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Abstract

Microalbuminuria is an increase in urinary albumin not detected by conventional dipstick testing and is present in 20% of patients with non–insulin-dependent diabetes mellitus (NIDDM). Mortality in NIDDM patients with microalbuminuria is 60% at 8 years and is mainly due to cardiovascular disease. Because many deaths occur without warning symptoms, we have compared the prevalence and severity of silent myocardial ischemia in asymptomatic NIDDM patients with and without microalbuminuria. We have performed a cross-sectional, case-control study of asymptomatic NIDDM patients attending hospital diabetes clinics. Forty-three patients with microalbuminuria were matched for age, gender, diabetes duration, and smoking status with 43 normoalbuminuric patients. A symptom-limited exercise stress test was performed and reported blind to patient status. The degree of electrocardiographic ST-segment depression, exercise time, work performed, and maximum heart rate with exercise were recorded. Patients with microalbuminuria had a higher prevalence of ischemic response (>1 mm ST depression) (65% vs 40%, p = 0.016), reduced total exercise time (5 vs 7 minutes, p <0.001), reduced work (6 vs 8 METs, p<0.001), and reduced age-predicted maximum heart rate (94% vs 101%, p = 0.004). In multiple logistic regression, albumin excretion rate was shown to be the strongest independent predictor of ischemic response (p = 0.03). Silent myocardial ischemia is common in asymptomatic NIDDM patients but is more common in those with microalbuminuria. In these subjects, the higher prevalence of ischemic response at low workloads suggests a higher probability of future coronary events, and possibly a higher probability of potentially treatable coronary artery disease.

Section snippets

Patient selection

NIDDM patients (according to World Health Organization criteria), aged 45 to 75 years, were recruited from hospital diabetic clinics in Newcastle upon Tyne, United Kingdom. Exclusion criteria were: NIDDM for <1 year, history of myocardial infarction, history of angina, as defined by the Rose questionnaire,12 heart failure, uncontrolled hypertension (blood pressure >180/100 mm Hg), significant aortic stenosis, cardiomyopathy, known serious arrhythmias, left bundle branch block, previous coronary

Clinical and biochemical characteristics

The success of the matching was demonstrated by no significant differences in age, gender, known diabetes duration, or smoking status between groups (Table I). Clinical assessment showed that patients with microalbuminuria were more likely to have symptoms of intermittent claudication, peripheral neuropathy, and a history of higher alcohol intake than those with normoalbuminuria. Those with microalbuminuria also had increased body mass index, waist hip ratio, systolic blood pressure, and

Discussion

We have shown that silent myocardial ischemia is common in asymptomatic NIDDM patients both with (65%) and without microalbuminuria (40%), but in those with microalbuminuria, it is more common and occurs at lower workloads. We have demonstrated that in asymptomatic NIDDM patients, the presence of microalbuminuria is the strongest independent predictor of ischemic response on treadmill exercise testing.

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    ☆

    This study was supported by grants from The Northern Region Small Grants Committee, The Freeman Hospital Board of Trustees, Newcastle upon Tyne, United Kingdom; Novo Nordisk, Crawley, West Sussex; Bayer plc, Newbury, Berkshire; and Eli Lilly and Co. Ltd., Basingstoke, Hampshire, United Kingdom.

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