(Circulation. 1995;91:831-837.)
© 1995 American Heart Association, Inc.
Articles |
Hyperinsulinemic Microalbuminuria
A New Risk Indicator for Coronary Heart Disease
From the Department of Medicine, Kuopio University Hospital, Kuopio, Finland.
Correspondence to Markku Laakso, MD, Department of Medicine, University of Kuopio, 70210 Kuopio, Finland.
Background Both hyperinsulinemia and microalbuminuria have been shown to increase coronary heart disease (CHD) risk, but the interaction among hyperinsulinemia, microalbuminuria, and the risk for CHD has not been investigated in previous studies.
Methods and Results The risk of CHD in relation to
hyperinsulinemia and microalbuminuria was examined in a cohort of 1069
elderly nondiabetic subjects from Kuopio, east Finland, during 3.5
years of follow-up. The overall incidence of CHD death was 2.8%, and
6.9% of study subjects died of CHD or had a nonfatal myocardial
infarction (later referred to as all CHD events). In the highest
fasting-insulin quintile (fasting insulin 
114.0 pmol/L), there was a
slightly but insignificantly higher incidence rate of both CHD
mortality and all CHD events compared with lower quintiles. The
incidence rates of CHD mortality and all CHD events were significantly
higher in the highest urinary albumin/creatinine ratio (ACR) quintile
(ACR 3.22 mg/mmol) compared with lower quintiles (P<.05
and P<.01, respectively). Hyperinsulinemic microalbuminuria
(simultaneous presence of fasting insulin 114.0 pmol/L and ACR 3.22
mg/mmol) markedly increased the risk of CHD mortality (12.5%,
P<.001) and all CHD events (18.8%, P<.001)
compared with normoinsulinemic subjects without microalbuminuria (2.2%
and 5.8%, respectively). In univariate logistic regression analyses,
hyperinsulinemic microalbuminuria was a strong predictor of both CHD
death (odds ratio [OR], 5.93; P<.001) and all CHD events
(OR, 3.39; P=.002). Multivariate logistic regression
analyses were also performed, including sex, current smoking, waist-hip
ratio, systolic blood pressure, and HDL cholesterol, with insulin, ACR,
or both as independent variables. Even after adjustment for these
variables, hyperinsulinemic microalbuminuria remained a strong
predictor of CHD death (OR, 7.91; P<.001) and all CHD
events (OR, 2.95; P=.014). The group with hyperinsulinemic
microalbuminuria was characterized by the most adversely affected risk
factor pattern (high triglycerides 2.3 mmol/L, low HDL cholesterol
0.9 mmol/L in men and 1.20 mmol/L in women, and hypertension).
Conclusions Simultaneous occurrence of hyperinsulinemia and microalbuminuria identifies a group of subjects with a highly increased risk for CHD in elderly nondiabetic subjects.
Key Words: insulin • microalbuminuria • coronary disease
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|
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|
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|
|
|
|
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|
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|
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|
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|
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