Coronary CT angiography features of ruptured and high-risk atherosclerotic plaques: Correlation with intra-vascular ultrasound

BACKGROUND: Features of ruptured and high-risk plaque have been described on coronary computed tomography angiography (coronary CTA), but not systematically assessed against intravascular ultrasound (IVUS). We examined the ability of coronary CTA to identify IVUS defined ruptured plaque and Virtual Histology Intravascular Ultrasound (VH-IVUS) defined thin-cap fibroatheroma (TCFA). METHODS: Sixty-three patients (32 with acute coronary syndrome and 31 with stable angina) underwent coronary CTA, IVUS and VH-IVUS. Plaque rupture on CTA was defined as intra-plaque contrast and its frequency compared with IVUS-defined plaque rupture. We then examined the relationship of conventional coronary CTA high-risk features (low attenuation plaque, positive remodeling, spotty calcification and the Napkin-Ring sign) in VH-IVUS-defined TCFA. We compared these with a novel index based on quantifying the ratio of necrotic core to fibrous plaque using x-ray attenuation cut-offs derived from the relationship of plaque to luminal contrast attenuation. RESULTS: Of the 71 plaques interrogated with IVUS, 39 were ruptured. Coronary CTA correctly detected 13-ruptured plaques with 3 false positives giving high specificity (91%) but low sensitivity (33%). None of the conventional coronary CTA high-risk features were significantly more frequent in the higher-risk (VH-IVUS defined thin-cap) compared with thick-cap fibroatheroma. However, the new index (necrotic core/fibrous plaque ratio) was higher in thin-cap (mean 0.90) vs. thick-cap fibroatheroma (mean 0.59), p < 0.05. CONCLUSIONS: Compared with intravascular ultrasound, coronary CTA identifies ruptured plaque with good specificity but poor sensitivity. We have identified a novel high-risk feature on coronary CTA (necrotic core/fibrous plaque ratio that is associated with VH-IVUS defined-TCFA.Supported by a British Heart Foundation grant FS/10/025/2819

Enhanced superoxide anion production in experimental venous bypass grafts is mediated by NAD(P)H oxidase

Background: Enhanced superoxide (SO) production and its interaction with nitric oxide (NO) is an important feature of vascular disease states. Accelerated atherosclerosis in vein graft (VG) disease is a major clinical problem, resulting from intimal hyperplasia and deficient NO-mediated endothelial function. SO's role in VG pathobiology remains unclear. Methods: We compared jugular-carotid interposition bypass grafts with native jugular veins in normocholesterolemic New Zealand White rabbits (n=16). Some animals underwent sham surgical isolation of the ungrafted jugular vein (JV) as added controls. VG and JV were harvested at 28 days and analysed by lucigenin-enhanced chemiluminescence to measure SO production, and Western blotting and immunohistochemistry to detect the p22phox subunit of the NAD(P)H oxidase enzyme. Results: Basal SO production was increased in VG (n=9) compared with both native and sham-operated JV (n=12; p&lt;0.05). The flavin oxidase inhibitor diphenyleneiodonium reduced SO generation in VG by 63% (p&lt;0.05) although other oxidase enzyme inhibitors had no significant effect. Furthermore, NADH stimulated SO production from VG significantly more than from JV in the same animal (6.3±0.9 vs 2.3±0.6 RLU/s/μg protein; p&lt;0.005). Subcellular fractionation revealed &gt;95% of the NADH-dependent activity in VG was in the particulate (membrane-bound) fraction. Western blotting demonstrated increased amounts of the p22phox subunit of the NAD(P)H oxidase in VG compared with paired JV, and this was localised by immunohistochemical staining to smooth muscle cells in the hyperplastic intima of VG. Conclusions: These data indicate (1) SO production is increased in VG compared with ungrafted and sham-operated JV in normocholesterolemic animals; (2) the major source of enhanced SO production in VG is the NAD(P)H oxidase enzyme, which is present in increased amounts in VG; and (3) the major cell type expressing p22phox is intimal smooth muscle cells. These findings suggest a possible role for SO production in VG pathobiology and in mediating deficient NO bioactivity