From the Cardiac Catheterization Unit (F.R., G.S., A.D.), Division of
Cardiology (A.V., E.V.), and Laboratory for Clinical Biochemistry (T.C.),
Ospedale Santa Croce, Cuneo, Italy, and Dipartimento di Genetica (G.M., E.C.,
G.B., A.P.), Biologia e Biochimica e Centro CNR–CIOS, Universita'
di Torino, Italy.
Correspondence to Giuseppe Steffenino, MD, Laboratorio di Emodinamica, Ospedale Santa Croce, Via M Coppino, 26, 12100 Cuneo, Italy. E-mail emodinam{at}www.lrcser.it
Background—Tissue proliferation is
almost invariably observed in recurrent lesions within stents, and ACE,
a factor of smooth muscle cell proliferation, may play an important
role. Plasma ACE level is largely controlled by the insertion/deletion
(I/D) polymorphism of the enzyme gene. The
association among restenosis within coronary stents,
plasma ACE level, and the I/D polymorphism is
analyzed in the present prospective study.
Methods and Results—One hundred seventy-six consecutive patients
with successful, high-pressure, elective stenting of de novo lesions in
the native coronary vessels were considered. At follow-up
angiography, recurrence was observed in 35 patients (19.9%).
Baseline clinical and demographic variables, plasma glucose and
serum fibrinogen levels, lipid profile, descriptive and quantitative
angiographic data, and procedural variables were not significantly
different in patients with and without restenosis; mean plasma
ACE levels (±SEM) were 40.8±3.5 and 20.7±1.0 U/L, respectively
(P<.0001). Diameter stenosis percentage and
minimum luminal diameter at 6 months showed statistically significant
correlation with plasma ACE level (r=.352 and -.387,
respectively P<.001). Twenty-one of 62 patients
(33.9%) with D/D genotype, 13 of 80 (16.3%)
with I/D genotype, and 1 of 34 (2.9%) with
I/I genotype showed recurrence; the
restenosis rate for each genotype is consistent
with a codominant expression of the allele D.
Conclusions—In a selected cohort of patients, both the
D/D genotype of the ACE gene, and high plasma
activity of the enzyme are significantly associated with in-stent
restenosis. Continued study with clinically different subsets
of patients and various stent designs is warranted.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Plasma Activity and Insertion/Deletion Polymorphism of Angiotensin I–Converting Enzyme
A Major Risk Factor and a Marker of Risk for Coronary Stent Restenosis
Key Words: stents • genes • angiotensin • follow-up studies • 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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