Angiotensin-converting enzyme inhibition with enalapril slows progressive intima-media thickening of the common carotid artery in patients with non-insulin-dependent diabetes mellitus.
OBJECTIVE
Whether angiotensin-converting enzyme (ACE) inhibitors have any clinically significant antiatherogenic effects in humans remains unproven. We undertook a prospective randomized clinical trial of 98 patients with non-insulin-dependent diabetes mellitus (NIDDM) to examine the efficacy of ACE inhibition with enalapril for preventing intima-media (IM) thickening of the carotid wall as measured ultrasonographically.


METHODS
Ninety-eight NIDDM patients were randomly assigned either to enalapril at 10 mg/d (n=48) or to a control group (n=50); the planned duration of the trial was 2 years. All patients were seen at baseline (study entry) and 2 subsequent formal annual evaluations, in addition to standard clinical management for NIDDM. IM thickening and vascular lumen diameters were determined for all patients on the basis of baseline and 2 subsequent annual evaluations with carotid ultrasonography. We performed an intent-to-treat analysis to assess changes in IM thickening over the course of the study.


RESULTS
Annual IM thickening measurements of the right and left common carotid arteries were 0.01+/-0.02 and 0.01+/-0.02 mm/y in the enalapril-treated group and 0.02+/-0.03 and 0.02+/-0.02 mm/y in the control group, respectively (P<0.05). From regression analysis, annual IM thickening was found to be predicted by enalapril use, sex, and insulin use (F(3,94)=3.86, P=0.012). When we controlled for these other variables, enalapril use reduced annual IM thickening of right and left common carotid arteries by 0.01+/-0.004 mm/y relative to the control group over the course of this study.


CONCLUSIONS
Long-term treatment with an ACE inhibitor (enalapril) slows progressive IM thickening of the common carotid artery in NIDDM patients.
Hosomi
N
N
Second Department of Internal Medicine, Kagawa Medical University School of Medicine, Kagawa, Japan.
Mizushige
K
K
Ohyama
H
H
Takahashi
T
T
Kitadai
M
M
Hatanaka
Y
Y
Matsuo
H
H
Kohno
M
M
Koziol
J A
JA
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001161:Arteriosclerosis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D002340:Carotid Artery Diseases / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D018450:Disease Progression; D004656:Enalapril / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000473:pathology; D017540:Tunica Media / Q000000981:diagnostic imaging / Q000473:pathology; D014463:Ultrasonography
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril