The aim of the present study was to analyse the long-term histology and immunohistochemistry of the plaque composition and cellular infiltration of SVGs (saphenous vein grafts) containing metallic stents. Percutaneous interventions in SVGs have a worse long-term clinical outcome compared with stenting of coronary arteries. Whether the pathological features of old degenerated SVGs condition the efficacy of drug-eluting stents is also unknown. Histology and immunohistochemistry of seven SVGs in the coronary circulation containing 12 metallic stents implanted 5 to 61 months before retrieval were analysed in patients undergoing a second aorto-coronary bypass surgery at a mean time of 11±6 years. The pathology of the old SVGs showed an important thrombotic and necrotic composition of the plaque, with plaque protrusion through the stent wires and a fragile media layer that could easily be damaged by stent placement with subsequent neointimal proliferation; indeed, stents with medial fracture had significantly greater mean neointimal thickness than those without (1.37±0.68 compared with 0.81±0.47 mm 2 ; P <0.02). Neointimal inflammatory cell density correlated with increased neointimal thickness in patent vessels ( r 2 =0.43, P <0.001). Immunostaining showed the total absence of ERs (oestrogen receptors), a poor cellular proliferative state as indicated by the presence of the Ki-67 marker, and persistent inflammation close to the stent wires as revealed by KP-1 and ACE (angiotensin-converting enzyme) immunostaining in most inflammatory cells in contact with the metal. These pathological findings may contribute to the more severe progression of disease and worse clinical outcome observed after conventional stented angioplasty of SVGs and might also interfere with the efficacy of drug-eluting stents in this specific atherosclerotic milieu.

The ID (insertion/deletion) polymorphism of the ACE (angiotensin-converting enzyme) gene controls plasma ACE levels. Both have been correlated with ISR (in-stent restenosis) in preliminary analyses, but not confirmed in larger studies. In the present study, baseline and 6-month quantitative coronary analysis were performed in 897 patients who had stent implantation and the ID polymorphism genotyped. Plasma ACE levels were measured in 848 patients (95%). Restenosis rates among genotypes were 31.2% DD, 25.5% ID and 28.8% II (not significant). Plasma ACE levels were significantly higher in restenotic patients compared with patients without restenosis (30.7±18.6 units/l compared with 22.8±12.8 units/l; P =0.0001) and a strong independent predictor of ISR [OR (odds ratio)=3.70; 95% CI (confidence interval), 2.40–5.71; P <0.0001], except in diabetics. In the subgroup of diabetics and patients with AMI (acute myocardial infarction), the DD genotypes actually had a lower risk of ISR than the II genotypes (diabetics, OR=0.16; 95% CI, 0.04–0.69; P =0.014; and patients with AMI, OR=0.21; 95% CI, 0.061–0.749; P =0.016). After exclusion of diabetics and patients with AMI, ISR rates for genotypes in 632 patients were 31.7% DD, 24.3% ID and 17.6% II ( P =0.02; DD compared with non-DD OR=1.57; 95% CI, 1.09–2.25). The association between the D allele and ISR observed in selected populations does not hold with a larger sample size. Other than sample size, clinical variables can modulate the association between ID polymorphism and ISR. Plasma ACE level is a risk factor for ISR, independently of the ID genotype.