Predictors of coronary in-stent restenosis: importance of angiotensin-converting enzyme gene polymorphism and treatment with angiotensin-converting enzyme inhibitors.
OBJECTIVE
This study aimed to clarify the role of the angiotensin-converting enzyme (ACE) gene polymorphism in the development of in-stent restenosis.


BACKGROUND
In-stent restenosis occurs after treatment of coronary artery stenosis in 12% to 32% of coronary interventions with stents. Experimental and clinical studies have suggested that the deletion/insertion (D/I) polymorphism of the ACE gene plays a role in this.


METHODS
Quantitative coronary angiography before, immediately after and six months after stent implantation were compared in 369 patients, in whom D/I typing of the ACE gene was performed.


RESULTS
At follow-up we found no differences between the three genotypes in minimal lumen diameter (homozygotes with two deletion alleles in the ACE gene [DD], 2.20 mm; heterozygotes with one deletion and one insertion allele in the ACE gene [DI], 2.19 mm; and homozygotes with two insertion alleles in the ACE gene [II], 2.25 mm). The corresponding diameter stenoses were: DD: 25%, DI: 27%, II: 27% (p = NS), and the frequency of restenosis (>50% diameter stenosis) was: DD: 15.7%, DI: 11.0% and II: 16.4% (p = NS). Logistic regression analysis identified diabetes (odds ratio [OR]: 3.0, 95% confidence interval [CI]: 1.0 to 8.7), lesion length (OR: 1.1, 95% CI: 1.01 to 1.30) and minimal lumen diameter immediately after the intervention (OR: 0.3, 95% CI: 0.14 to 0.85) as predictors of in-stent restenosis. In a post hoc analysis of patients treated versus those not treated with an ACE-inhibitor antagonist or an angiotensin receptor antagonist, we found an increased frequency of in-stent restenosis in the DD genotypes (40% vs. 12%, p = 0.006).


CONCLUSIONS
The D/I polymorphism is not an independent predictor of coronary in-stent restenosis in general, but it may be of clinical importance in patients treated with ACE inhibitors or angiotensin receptor antagonists.
Jørgensen
E
E
Department of Cardiology, The Heart Centre, Rigshospitalet, Copenhagen, Denmark. erikj@rh.dk
Kelbaek
H
H
Helqvist
S
S
Jensen
G V
GV
Saunamäki
K
K
Kastrup
J
J
Havndrup
O
O
Bundgaard
H
H
Kyst Madsen
J
J
Christiansen
M
M
Andersen
P S
PS
Reiber
J H
JH
D000328:Adult; D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D017023:Coronary Angiography; D003327:Coronary Disease / Q000000981:diagnostic imaging / Q000235:genetics* / Q000628:therapy*; D016172:DNA Fingerprinting; D005260:Female; D005500:Follow-Up Studies; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011237:Predictive Value of Tests; D012008:Recurrence; D012307:Risk Factors; D015607:Stents / Q000009:adverse effects; D017211:Treatment Failure
D000806:Angiotensin-Converting Enzyme Inhibitors; D007703:Peptidyl-Dipeptidase A