Joseph H. Rapp

BACKGROUND: The benefit of coronary-artery revascularization before elective major vascular surgery is unclear. METHODS: We randomly assigned patients at increased risk for perioperative cardiac complications and clinically significant coronary artery disease to undergo either revascularization or no revascularization before elective major vascular surgery. The primary end point was long-term mortality. RESULTS: Of 5859 patients scheduled for vascular operations at 18 Veterans Affairs medical centers, 510 (9 percent) were eligible for the study and were randomly assigned to either coronary-artery revascularization before surgery or no revascularization before surgery. The indications for a vascular operation were an expanding abdominal aortic aneurysm (33 percent) or arterial occlusive disease of the legs (67 percent). Among the patients assigned to preoperative coronary-artery revascularization, percutaneous coronary intervention was performed in 59 percent, and bypass surgery was performed in 41 percent. The median time from randomization to vascular surgery was 54 days in the revascularization group and 18 days in the group not undergoing revascularization (P<0.001). At 2.7 years after randomization, mortality in the revascularization group was 22 percent and in the no-revascularization group 23 percent (relative risk, 0.98; 95 percent confidence interval, 0.70 to 1.37; P=0.92). Within 30 days after the vascular operation, a postoperative myocardial infarction, defined by elevated troponin levels, occurred in 12 percent of the revascularization group and 14 percent of the no-revascularization group (P=0.37). CONCLUSIONS: 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.

BACKGROUND: Whether elective surgical repair of small abdominal aortic aneurysms improves survival remains controversial. METHODS: We randomly assigned patients 50 to 79 years old with abdominal aortic aneurysms of 4.0 to 5.4 cm in diameter who did not have high surgical risk to undergo immediate open surgical repair of the aneurysm or to undergo surveillance by means of ultrasonography or computed tomography every six months with repair reserved for aneurysms that became symptomatic or enlarged to 5.5 cm. Follow-up ranged from 3.5 to 8.0 years (mean, 4.9). RESULTS: A total of 569 patients were randomly assigned to immediate repair and 567 to surveillance. By the end of the study, aneurysm repair had been performed in 92.6 percent of the patients in the immediate-repair group and 61.6 percent of those in the surveillance group. The rate of death from any cause, the primary outcome, was not significantly different in the two groups (relative risk in the immediate-repair group as compared with the surveillance group, 1.21; 95 percent confidence interval, 0.95 to 1.54). Trends in survival did not favor immediate repair in any of the prespecified subgroups defined by age or diameter of aneurysm at entry. These findings were obtained despite a low total operative mortality of 2.7 percent in the immediate-repair group. There was also no reduction in the rate of death related to abdominal aortic aneurysm in the immediate-repair group (3.0 percent) as compared with the surveillance group (2.6 percent). Eleven patients in the surveillance group had rupture of abdominal aortic aneurysms (0.6 percent per year), resulting in seven deaths. The rate of hospitalization related to abdominal aortic aneurysm was 39 percent lower in the surveillance group. CONCLUSIONS: Survival is not improved by elective repair of abdominal aortic aneurysms smaller than 5.5 cm, even when operative mortality is low.

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. MATERIALS AND METHODS: Eight patients with transient ischemic attacks who underwent carotid CTA and "en bloc" endarterectomy were enrolled in a prospective study. An ex vivo micro-CT study of each endarterectomy specimen was obtained, followed by histologic examination. A systematic comparison of CTA images with histologic sections and micro-CT images was performed to determine the CT attenuation associated with each component of the atherosclerotic plaques. A computer algorithm was subsequently developed that automatically identifies the components of the carotid atherosclerotic plaques, based on the density of each pixel. A neuroradiologist's reading of this computer analysis was compared with the interpretation of the histologic slides by a pathologist with respect to the types and characteristics of the carotid plaques. RESULTS: There was a 72.6% agreement between CTA and histologic examination in carotid plaque characterization. CTA showed perfect concordance for calcifications. A significant overlap between densities associated with lipid-rich necrotic core, connective tissue, and hemorrhage limited the reliability of individual pixel readings to identify these components. However, CTA showed good correlation with histologic examination for large lipid cores (kappa = 0.796; P < .001) and large hemorrhages (kappa = 0.712; P = .102). CTA performed well in detecting ulcerations (kappa = 0.855) and in measuring the fibrous cap thickness (R(2) = 0.77; P < .001). CONCLUSION: The composition of carotid atherosclerotic plaques determined by CTA reflects plaque composition defined by histologic examination.

We isolated and characterized immunoreactive apolipoprotein B (apoB)-containing lipoproteins from human atherosclerotic plaque and plasma to determine whether very-low-density lipoprotein (VLDL) can enter and become incorporated into the atherosclerotic lesion and how plaque apoB-containing 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 < d < 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 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.(ABSTRACT TRUNCATED AT 250 WORDS)

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 [3H]SM-LDL was incubated with strips of rabbit aorta ex vivo, a portion of the LDL was retained, and the [3H]SM of this portion, but not that of unretained LDL, was hydrolyzed to [3H]ceramide by a nonlysosomal arterial hydrolase. In summary, LDL retained in atherosclerotic lesions is acted upon by an arterial-wall SMase, which may participate in LDL aggregation and possibly other SMase-mediated processes during atherogenesis.