Significance of Silent Ischemia and
Microalbuminuria in Predicting Coronary
Events in Asymptomatic Patients With Type 2 Diabetes
Martin K. Rutter, MB CHB, MRCP,* Shahid T. Wahid, MB BS, MRCP,*
Janet M. McComb, MD, FRCP,† Sally M. Marshall, MD, FRCP*
Newcastle upon Tyne, United Kingdom
The aim of this study was to investigate the relationships between future coronary heart
disease (CHD) events and baseline silent myocardial ischemia (SMI) and microalbuminuria
(MA) in subjects with type 2 diabetes (T2D) free from known CHD.
Coronary heart disease is often asymptomatic in subjects with diabetes. There is limited
information on the prognostic value of SMI and MA in this group.
Eighty-six patients with T2D and no history of CHD were studied (43 with MA individually
matched with 43 normoalbuminuric patients; mean [SD] age 62 [?7] years, 62 men).
Metabolic assessment, three timed overnight urine collections for albumin excretion rate, a
treadmill exercise test and ankle brachial index (ABI) were performed at baseline. Patients
were followed for 2.8 years.
Forty-five (52%) patients had SMI during treadmill testing. At review, there had been 23
coronary (CHD) events in 15 patients. Univariate Cox regression analysis showed that CHD
events were significantly related to baseline ABI (p ? 0.014), SMI (p ? 0.020), MA (p ?
0.046), 10-year Framingham CHD risk ?30% (p ? 0.035) and fibrinogen (p ? 0.026). In
multivariate analysis, SMI was the strongest independent predictor of CHD events (p ?
0.008); risk ratio (95% confidence interval) for SMI: 21 (2 to 204). In the prediction of CHD
events, SMI showed higher sensitivity and positive predictive value than MA or Framingham
calculated CHD risk.
CONCLUSIONS The presence of baseline SMI and MA are associated with future CHD events in
asymptomatic patients with T2D and may be of practical use in risk stratification.
Coll Cardiol 2002;40:56–61) © 2002 by the American College of Cardiology Foundation
Coronary heart disease (CHD) is the leading cause of death
in patients with type 2 diabetes (T2D), is often asymptom-
atic (1) and may present without warning as acute myocar-
dial infarction (AMI), heart failure, arrhythmia or sudden
death. In AMI (2) and heart failure (3), mortality is
increased in the presence of T2D, thus emphasizing the
potential value of identifying high-risk asymptomatic indi-
viduals with diabetes.
Microalbuminuria (MA) is present in approximately 25%
of patients with T2D (4) and is associated with a doubling
of the risk of early death, mainly from CHD (5). Mi-
croalbuminuria has been defined by consensus, based on risk
of renal disease, as a urinary albumin excretion rate between
20 and 200 ?g/min, though rates of ?10.6 ?g/min have
been linked to increased macrovascular events in T2D (6).
Silent myocardial ischemia (SMI) can be detected by
various methods (7,8). Using treadmill exercise testing, SMI
has been defined as exercise-induced ST-segment depres-
sion in the absence of CHD symptoms (9), and, in men free
from known CHD, this finding has been associated with
increased mortality (10,11). There is very little data on the
prognostic value of SMI, detected by any method, in
asymptomatic patients with T2D (7,12–14).
We have previously shown that T2D is associated with a
high prevalence of SMI, especially in those with MA (15).
This cohort, free from symptoms of CHD at baseline, has
been followed to determine the influence of SMI and MA
Patient population. Baseline clinical characteristics and
methods have been described previously (15). Briefly, 86
patients with T2D and no history of cardiac disease were
studied: 43 with MA (albumin excretion rate [AER] ? 10.5
to 200 ?g/min) individually matched with 43 normoalbu-
minuric patients (AER ? 10.5 ?g/min) for age (?2 years),
gender, diabetes duration (?3 years) and smoking status
Methods. All patients performed three timed overnight
urine collections to assess AER and treadmill exercise
testing for SMI. Ankle brachial index (ABI), echocardiog-
raphy, ambulatory blood pressure (BP) monitoring, auto-
From the *Department of Medicine, University of Newcastle upon Tyne, and the
†Regional Cardiothoracic Centre, Freeman Hospital, Newcastle upon Tyne, United
Kingdom. Supported by fellowships and grants from the Northern Regional Health
Authority, the Freeman Hospital Board of Trustees, Novo Nordisk Ltd., Eli Lilly,
Bayer and GlaxoSmithKlein.
Manuscript received September 11, 2001; revised manuscript received March 28,
2002, accepted April 5, 2002.
Journal of the American College of Cardiology
© 2002 by the American College of Cardiology Foundation
Published by Elsevier Science Inc.
Vol. 40, No. 1, 2002
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Rutter et al.
Silent Ischemia, MA and Diabetes