ACE D/I Polymorphism and Incidence of Post-PTCA Restenosis

Abstract

Abstract-Early restenosis is the major complication of percutaneous transluminal coronary angioplasty (PTCA), occurring in Ϸ30% of all initially successful procedures. The D/I polymorphism of the ACE gene, which has variably been reported to represent a risk factor for manifestations of ischemic heart disease, has recently been implicated in the pathophysiology of restenosis after PTCA by some investigators but not by others. All studies conducted thus far involved relatively small sample sizes. We investigated the possible association of ACE D/I genotype and post-PTCA restenosis in a large, prospective sample of patients followed by quantitative coronary angiography. The ACE D/I gene polymorphism was characterized in a cohort of 779 patients, of whom 342 (cases) had developed restenosis (as defined by Ͼ50% loss of lumen compared with immediate postprocedure results) at repeat quantitative coronary angiography at 6 months after PTCA. Allele frequencies for the ACE D and I alleles were 0.58 and 0.42 in cases and 0.58 and 0.42 in control subjects. All observed genotype frequencies were in Hardy-Weinberg equilibrium. There was no evidence for an association between genotype and restenosis or degree of lumen loss. The data from this largest study of its kind conducted so far provide no evidence for an association of the ACE D/I allelic polymorphism with incidence of restenosis after PTCA. On the basis of the power of this study, we conclude that in a general population, the ACE D/I polymorphism is not a useful marker to assess risk of post-PTCA restenosis. (Hypertension. 2001;37:851-855.)

Is AV Fistula Patency Associated with Angiotensin-Converting Enzyme (ACE) Polymorphism and ACE Inhibitor Intake?

“…Patients who bear the DD genotype of the ACE gene and who are thus genetically prone to increased ACE activity [14] were initially suggested to have a greater risk of restenosis after percutaneous coronary angioplasty compared to patients with the ID or II genotype [21]. However, larger and more rigorous studies [22][23][24] found weaker associations between the ACE DD genotype and restenosis after percutaneous coronary angioplasty, with or without additional stenting. In accordance, a meta-analysis reported an inverse correlation between study population size and magnitude of relative risk associated with I/D polymorphism [25].…”

“…It has been suggested before [23] that intimal hyperplasia in experimental models of vascular injury, in which smooth muscle cell proliferation is of major importance, may differ from the pathophysiological characteristics of restenosis after percutaneous coronary angioplasty in humans, in which adventitial remodeling and smooth muscle cell migration rather than proliferation appear to be the principle mechanisms. The same may hold true for AV fistula stenosis, in which adventitial remodeling and migration of smooth muscle cells and of fibroblasts to the intima came to be considered key events [31].…”

Association study of the I/D polymorphism and plasma angiotensin-converting enzyme (ACE) as risk factors for stent restenosis

“…Following these initial observations, two larger studies performed in Germany [3] and Denmark [4] yielded negative results, casting doubts about the predictive value of the ID polymorphism in this process. The study of the ID polymorphism as a marker of risk for restenosis after balloon angioplasty resulted in similarly contradictory findings between a small positive study [5] and subsequent negative larger investigations [6]. Recently, a metaanalysis has assessed the value of the D allele as a marker for restenosis.…”

Angiotensin converting enzyme insertion or deletion polymorphism and coronary restenosis: meta-analysis of 16 studies

“…As the angiotensin converting enzyme insertion or deletion (I/D) polymorphism is strongly associated with plasma and cellular angiotensin converting enzyme concentrations, it has been considered a strong candidate 2. It has been suggested that the incidence of coronary restenosis after a percutaneous coronary intervention is much higher in patients with the angiotensin converting enzyme DD genotype (which is associated with particularly high plasma angiotensin converting enzyme levels) than in others, but published observational studies are conflicting 3 – 18. To help clarify the evidence we considered all available relevant studies in a meta-analysis.…”