Survival is not improved by elective repair of abdominal aortic aneurysms smaller than 5.5 cm, even when operative mortality is low.

Coronary-artery revascularization before elective vascular surgery does not significantly alter the long-term outcome. On the basis of these data, a strategy of coronary-artery revascularization before elective vascular surgery among patients with stable cardiac symptoms cannot be recommended.

The subendothelial aggregation and retention of low density lipoprotein (LDL) are key events in atherogenesis, but the mechanisms in vivo are not known. Previous studies have shown that treatment of LDL with bacterial sphingomyelinase (SMase) in vitro leads to the formation of lesion-like LDL aggregates that become retained on extracellular matrix and stimulate macrophage foam cell formation. In addition, aggregated human lesional LDL, but not unaggregated lesional LDL or plasma LDL, shows evidence of hydrolysis by an arterial wall SMase in vivo, and several arterial wall cell types secrete a SMase (S-SMase). S-SMase, however, has a sharp acid pH optimum using a standard in vitro SMmicelle assay. Thus, a critical issue regarding the potential role of S-SMase in atherogenesis is whether the enzyme can hydrolyze lipoprotein-SM, particularly at neutral pH. We now show that S-SMase can hydrolyze and aggregate native plasma LDL at pH 5.5 but not at pH 7.4. Remarkably, LDL modified by oxidation, treatment with phospholipase A 2 , or enrichment with apolipoprotein CIII, which are modifications associated with increased atherogenesis, is hydrolyzed readily by S-SMase at pH 7.4. In addition, lipoproteins from the plasma of apolipoprotein E knock-out mice, which develop extensive atherosclerosis, are highly susceptible to hydrolysis and aggregation by S-SMase at pH 7.4; a high SM:PC ratio in these lipoproteins appears to be an important factor in their susceptibility to S-SMase. Most importantly, LDL extracted from human atherosclerotic lesions, which is enriched in sphingomyelin compared with plasma LDL, is hydrolyzed by S-SMase at pH 7.4 10-fold more than same donor plasma LDL, suggesting that LDL is modified in the arterial wall to increase its susceptibility to S-SMase. In summary, atherogenic lipoproteins are excellent substrates for S-SMase, even at neutral pH, making this enzyme a leading candidate for the arterial wall SMase that hydrolyzes LDL-SM and causes subendothelial LDL aggregation.

Aggregation and retention of LDL in the arterial wall are key events in atherogenesis, but the mechanisms in vivo are not known. Previous work from our laboratories has shown that exposure of LDL to bacterial sphingomyelinase (SMase) in vitro leads to the formation of LDL aggregates that can be retained by extracellular matrix and that are able to stimulate macrophage foam cell formation. We now provide evidence that retained LDL is hydrolyzed by an arterial-wall SMase activity. First, we demonstrated that SMase-induced aggregation is caused by an increase in particle ceramide content, even in the presence of excess sphingomyelin (SM). This finding is compatible with previous data showing that lesional LDL is enriched in SM, though its ceramide content has not previously been reported. To address this critical compositional issue, the ceramide content of lesional LDL was assayed and, remarkably, found to be 10-50-fold enriched compared with plasma LDL ceramide. Furthermore, the ceramide was found exclusively in lesional LDL that was aggregated; unaggregated lesional LDL, which accounted for 20-25% of the lesional material, remained ceramide poor. When

BACKGROUND AND PURPOSE:Plaque morphologic features have been suggested as a complement to luminal narrowing measurements for assessing the risk of stroke associated with carotid atherosclerotic disease, giving rise to the concept of "vulnerable plaque." The purpose of this study was to evaluate the ability of multidetector-row CT angiography (CTA) to assess the composition and characteristics of carotid artery atherosclerotic plaques with use of histologic examination as the gold standard.

UPTURE OF ABDOMINAL AORtic aneurysm (AAA) can be prevented by elective surgical repair, but because most AAA never rupture, 1 elective repair is reserved for patients at high risk of rupture. The most commonly used predictor of rupture is the maximum diameter of the AAA. Two randomized trials found no reduction in mortality from repairing AAA smaller than 5.5 cm in patients at low operative risk. 2,3 No randomized trials are available in patients with larger AAA, and decision making in these patients is often complicated by advanced age and serious comorbidities. Surgery is usually deferred in highoperative-risk patients until the AAA attains a diameter at which the risk of rupture is thought to outweigh the operative risk. However, few data are available on the rupture risk of large AAA, resulting in substantial disagreement among experts. 4 We conducted a prospective observational Veterans Affairs Cooperative Study to determine the incidence of rupture in patients with large AAA for whom elective repair was not planned because of medical contraindications or patient refusal. METHODSEligible patients were those evaluated at 47 Veterans Affairs medical centers who were diagnosed as having AAA of at least 5.5 cm in diameter by ultrasonography or computed tomography (CT) within 3 months prior to enrollment and for

Endotoxemia stimulates many physiologic responses including disturbances in lipid metabolism. We hypothesized that this lipemia may be part of a defensive mechanism by which the body combats the toxic effects of circulating endotoxin. We tested the effects of mixtures of endotoxin, lipoproteins, and lipoprotein-free plasma and determined the ability of varying concentrations of human very low density lipoproteins (VLDL) and chylomicrons, as well as low density lipoproteins (LDL) and high density lipoproteins (HDL), and of the synthetic lipid emulsion SOYACAL to prevent endotoxin-induced death in mice. This study demonstrates that the triglyceride-rich VLDL and chylomicrons, as well as cholesterol-rich LDL and HDL, and cholesterol-free SOYACAL can protect against endotoxin-induced death. Protection required small amounts of lipoprotein-free plasma, and depended on the incubation time and the concentration of lipoprotein lipid. Despite stringent techniques to prevent exogenous endotoxin contamination eight of ten duplicate VLDL preparations contained endotoxin (5,755±3,514 ng endotoxin/mg triglyceride, mean±SEM) making the isolation of endotoxin-free VLDL difficult. In contrast, simultaneous preparations of LDL and HDL were relatively free of endotoxin contamination (3±3 and 320±319 ng/mg total cholesterol, respectively), suggesting that the contamination of VLDL occurs in vivo and not during the isolation procedure. These observations suggest a possible role for increased triglyceride-rich lipoproteins in the host's defense against endotoxemia and infection. (J. Clin. Invest. 1990.

We isolated and characterized immunoreactive apolipoprotein B (apoB) -containing lipoproteins from human atherosclerotic plaque and plasma to determine whether verylow-density lipoprotein (VLDL) can enter and become incorporated into the atherosclerotic lesion and how plaque apoBcontaining lipoproteins differ from apoB-containing lipoproteins isolated from plasma. Atherosclerotic plaques were obtained during aortic surgery and processed immediately. Lipoproteins were extracted from minced plaque in a buffered saline solution (extract A). In selected cases a second extraction was done after plaque was incubated with collagenase (extract B). Lipoproteins were then isolated from the extracts by anti-apoB immunosorption and separated into VLDL+intermediate-density lipoprotein (IDL) (d< 1.019 g/mL) and low-density lipoprotein (LDL) (1.019«f< 1.070 g/mL) fractions by ultracentrifugation. The VLDL+IDL fractions from plaque contained more than one third of the total apoB-associated lipoprotein cholesterol in both extracts A and B. The lipid composition of VLDL+IDL in both extracts was related to that of plasma VLDL+IDL By electron microscopy L ipoprotein infiltration into the artery wall is an essential event in the pathogenesis of atherosclerosis, but little is known about the process of lipoprotein infiltration and eventual entrapment in plaque. Even the identity of the lipoproteins involved has not been conclusively determined. It is generally agreed that low-density lipoproteins (LDL) have access to the artery wall, but very-low-density lipoproteins (VLDL) also may infiltrate the artery wall and directly contribute to atherogenesis. VLDL, particularly VLDL remnants, certainly have atherogenic potential.1 -2 Particles resembling VLDL remnants can be taken up by macrophages to produce foam cells, 3 -3 stimulate endothelial cells to express a monocyte-specific chemotactic factor, 6 and increase monocyte adherence to the endothelium. 7 Furthermore, varying amounts of labeled © 1994 American Heart Association, Inc.mean particle diameters of VLDL+IDL from extracts A and B were 9% and 23%, respectively, greater than VLDL+IDL diameters from plasma. Mean diameters of LDL from extracts A and B were 11% and 31% greater than LDL diameters from plasma. The apoE-apoB ratio of extract A VLDL+IDL was nearly twice that of plasma VLDL+IDL and severalfold higher than that of extract A LDL. Immunoblots of both VLDL+IDL and LDL from extract A demonstrated minimal fragmentation of apoB. These results demonstrate that (1) VLDL, VLDL remnants, or both, can enter human atherosclerotic plaque and become bound to the connective tissue matrix; (2) apoB-containing lipoproteins from plaque differ from plasma lipoproteins in size and apoE content; and (3) there appears to be minimal fragmentation of buffer-extractable apoB in plaque lipoproteins. (Arterioscler Thromb.