Neoatherosclerosis: another consequence of endothelial dysfunction?

T he long-term vascular response to coronary stenting can involve transformation of an otherwise benign neo-intima to one that resembles de novo atherosclerosis in an unstented vessel. The neointima may be infiltrated by foamy macrophages, undergo neovascularization, and develop unstable thin-cap fibroatheromas (TCFA) that contribute to neointimal disruption and thrombus formation in situ, similar to what is observed in the presence of a vulnerable plaque. 1,2 This process is known as neoatherosclerosis and is independently associated with mean in-stent neointimal thickness (odds ratio, 2.53; 95% confidence interval, 1.96– 3.27; P<0.001). When present, neoatherosclerosis leads to high rates of target lesion revascularization and stent thrombosis. There has been growing interest in the use of intravascu-lar optical coherence tomography (OCT) imaging to examine neointimal tissue characteristics and detect neoatherosclero-sis in bare metal stents (BMS) or drug-eluting stents (DES). Several small clinical studies using this approach found that early (<6 months) after BMS implantation, the neointima was thin and homogeneous; however, after 5 years, the neo-intima contained lipid pools and microvessels with areas of neointimal disruption consistent with neoatherosclerosis. 3 Similar neoatherosclerotic changes have been observed in DES neointima, although the overall lipid content is reportedly higher than what was seen in BMS. 4 In one study of 50 patients with DES in-stent restenosis, OCT revealed that 52% had ≥1 in-stent neointimal TCFA and 58% had ≥1 area of in-stent neointimal disruption, suggesting that neoathero-sclerosis was highly prevalent in restenosis. 5 DES neoathero-sclerosis exhibits spatial heterogeneity with a predilection for the proximal and distal segments of the stent and occurs more frequently when there is an adjacent lipid-rich plaque. 6 OCT studies also indicate that neoatherosclerosis occurs earlier in DES than BMS. Although neoatherosclerosis was observed in BMS after 5 years, it was detected in DES after a median of only 32.2 months. 5 While the aforementioned studies enrolled relatively few patients, their collective findings add to an accumulating body of evidence that identifies neoatheroscle-rosis as a significant contributor to late stent failure. 5 The OCT findings from clinical studies are supported by detailed histopathologic examinations of in-stent neoathero-sclerosis. Early pathological studies of BMS implanted for 2 to 7 years revealed chronic inflammation, neointimal microves-sels, and extracellular matrix collagen deposition and matrix metalloproteinase activity. 7 A contemporary autopsy study that analyzed 197 BMS and 209 DES found similar evidence of neointimal remodeling and confirmed that neoatheroscle-rosis occurred earlier in DES compared with BMS …