Limited impact of 2 g/day omega-3 fatty acid ethyl esters (Omacor®) on plasma lipids and inflammatory markers in patients awaiting carotid endarterectomy.

The objective of this study was to determine the effects of prescription omega-3 (n-3) fatty acid ethyl esters (Omacor®) on blood pressure, plasma lipids, and inflammatory marker concentrations in patients awaiting carotid endarterectomy. Patients awaiting carotid endarterectomy (n = 121) were randomised to Omacor® or olive oil as placebo (2 g/day) until surgery (median 21 days). Blood pressure, plasma lipids, and plasma inflammatory markers were determined. There were significant decreases in systolic and diastolic blood pressure and in plasma triglyceride, total cholesterol, low density lipoprotein-cholesterol, soluble vascular cellular adhesion molecule 1, and matrix metalloproteinase 2 concentrations, in both groups. The extent of triglyceride lowering was greater with Omacor® (25%) compared with placebo (9%). Soluble E-selectin concentration was significantly decreased in the Omacor® group but increased in the placebo group. At the end of the supplementation period there were no differences in blood pressure or in plasma lipid and inflammatory marker concentrations between the two groups. It is concluded that Omacor® given at 2 g/day for an average of 21 days to patients with advanced carotid atherosclerosis lowers triglycerides and soluble E-selectin concentrations, but has limited broad impact on the plasma lipid profile or on inflammatory markers. This may be because the duration of intervention was too short or the dose of n-3 fatty acids was too low.

Predictive haemodynamics in a one-dimensional human carotid artery bifurcation. Part II: Application to graft design.

A Bayesian surrogate modeling technique is proposed that may be able to predict an optimal bypass graft configuration for patients suffering with stenosis in the internal carotid artery (ICA). At the outset, this statistical technique is considered as a means for identifying key geometric parameters influencing haemodynamics in the human carotid bifurcation. This methodology uses a design of experiments (DoE) technique to generate candidate geometries for flow analysis. A pulsatile one dimensional Navier-Stokes solver incorporating fluid-wall interactions for a Newtonian fluid which predicts pressure and flow in the carotid bifurcation (comprising a stenosed segment in the internal carotid artery) is used for the numerical simulations. Two metrics, pressure variation factor (PVF) and maximum pressure (p(*)(m)) are employed to directly compare the global and local effects, respectively, of variations in the geometry. The values of PVF and p(*)(m) are then used to construct two Bayesian surrogate models. These models are statistically analyzed to visualize how each geometric parameter influences PVF and p(*)(m). Percentage of stenosis is found to influence these pressure based metrics more than any other geometric parameter. Later, we identify bypass grafts with optimal geometric and material properties which have low values of PVF on five test cases with 70%, 75%, 80%, 85%, and 90% stenosis in the ICA, respectively.5%, 80%, 85%, and 90% stenosis in the ICA, respectively.

Predictive haemodynamics in a one-dimensional human carotid artery bifurcation. Part I: Application to stent design.

A diagnostic technique is proposed to identify patients with carotid stenosis who could most benefit from angioplasty followed by stent implantation. This methodology involves performing a parametric study to investigate the haemodynamic behavior due to alterations in the stenosis shapes in the internal carotid artery (ICA). A pulsatile 1-D Navier-Stokes solver incorporating fluid-wall interactions for a Newtonian fluid which predicts pressure and flow in the human carotid artery bifurcation is used for the numerical simulations. In order to assess the performance of each individual geometry, we introduce pressure variation factor as a metric to directly compare the global effect of variations in the geometry. It is shown that the probability of an overall catastrophic effect is higher when the stenosis is present in the upstream segment of the ICA. Furthermore, maximum pressure is used to quantify the local effects of geometry changes. The location of the peak and extent of stenosis are found not to influence maximum pressure. We also show how these metrics respond after stent deployment into the stenosed part of the ICA. In particular, it is found that localized pressure peaks do not depend on the length of a stent. Finally, we demonstrate how these metrics may be applied to cost-effectively predict the benefit of stenting.

Differences in matrix metalloproteinase-1 and matrix metalloproteinase-12 transcript levels among carotid atherosclerotic plaques with different histopathological characteristics.

BACKGROUND AND PURPOSE: Previous studies have shown that atherosclerotic lesions express a number of matrix metalloproteinases (MMPs). Here we investigated whether transcript levels of MMP-1, -3, -7, -9, and -12 in carotid atherosclerotic plaques were correlated with histological features and clinical manifestations. METHODS: Atherosclerotic plaques (n=50) removed from patients undergoing carotid endarterectomy were classified histologically using a system proposed by Virmani et al, and MMP-1, -3, -7, -9, and -12 transcript levels in these tissues were quantified by real-time reverse-transcriptase polymerase chain reaction. RESULTS: Compared to plaques with a thick fibrous cap, those with a thin cap had a 7.8-fold higher MMP-1 transcript level (P=0.006). MMP-3, -7, and -12 were 1.5-fold, 1.8-fold, and 2.1-fold, respectively, higher in thin cap plaques, but the differences did not reach statistical significance. MMP-12 transcript levels were significantly increased in ruptured plaques compared with lesions without cap disruption (P=0.001). MMP-9 transcript levels were similar among the different types of lesion. MMP-1 and -12 transcript levels were significantly higher in plaques from patients with amaurosis fugax, than in those from asymptomatic patients (P=0.029 and P=0.008 for MMP-1 and MMP-12, respectively), than in those from patients with stroke (P=0.027 and P=0.001, respectively), and than in those from patients with transient ischemic attack (P=0.046 and P=0.008, respectively). CONCLUSIONS: These data support a role of MMP-1 and -12 in determining atherosclerotic plaque stability.

Peripheral arterial disease.

Peripheral arterial disease (PAD) is an atherosclerotic-driven condition that remains underdiagnosed and undertreated. In diabetic patients, PAD begins early, progresses rapidly, and is frequently asymptomatic, making it difficult to diagnose. Strict management of the metabolic instigators and use of screening techniques for PAD in diabetes can facilitate early diagnosis and reduce progression. Exercise is an equally effective treatment option in improving walking distance. Early revascularization must be offered early in suitable patients. Surgical bypass and endovascular revascularization are complementary and the choice of intervention should be applied appropriately by a multidisciplinary vascular team on a selective, patient-specific basis.

Peripheral arterial disease and bypass surgery in the diabetic lower limb.

PAD is very common in people with diabetes and is one of the strongest predictors of developing nonhealing foot ulcers and suffering amputation. There is strong evidence to show that early detection of PAD and revascularization will reduce amputations. Despite this, many patients have no vascular assessment even when they present with a foot ulcer or before amputation. Even when identified, patients are referred late, which worsens their outcome. Currently there is no evidence to support surgical revascularization over endovascular treatments, but in reality the techniques are complementary and the choice of revascularization procedure should be determined by an experienced multidisciplinary vascular team. Surgical revascularization can achieve good results but careful patient selection, operative planning, and the use of autologous vein are necessary. What is clearly apparent is that at present not enough patients are being offered revascularization to prevent amputation.

Management of median arcuate ligament syndrome in patients who require pancreaticoduodenectomy.

Pancreaticoduodenectomy is the standard treatment for localised neoplasms of the pancreatic head. The operation can be performed safely in specialist units but good outcome is compromised if postoperative blood flow to the liver and biliary tree is inadequate. Coeliac artery occlusion with blood supply to the liver arising from the superior mesenteric artery via the gastroduodenal artery is difficult to recognise, especially intraoperatively. Recognition of absent hepatic artery pulsation after occlusion of the gastroduodenal artery opens a dilemma: should the resection be abandoned or should vascular reconstruction be undertaken, adding risk to an already complex procedure? We describe two cases with a resectable pancreatic endocrine tumour in which coeliac artery occlusion caused by median arcuate ligament compression was identified from cross-sectional imaging and reconstructions. We highlight two different strategies to correct the vascular insufficiency and allow safe pancreatic resection.

Sex difference in composition of plaques of patients undergoing carotid endarterectomy.

Our study aimed to examine the hypothesis that women have more stable plaques (a lower proportion of lipid component and a higher proportion of fibrous tissue) compared to men. Plaque specimens of 141 consecutive carotid endarterectomy patients (60 females and 81 males) were studied. Medical histories were recorded and the plasma concentrations of cholesterol and inflammatory markers were measured. We found that plaques from females had significantly less lipid than those from males (p = .01): the mean percentage of plaque lipid for women and men was 47.8% and 58.2%, respectively. Plaques from females had more fibrous tissue than those from men (p = .02): the mean percentage of fibrous tissue for women and men was 38.8% and 29.8%, respectively. This study concluded that the histology of carotid artery plaques from women appears to be more stable than that of those from men.

Managing hypercholesterolemia and its correlation with carotid plaque morphology in patients undergoing carotid endarterectomy.

PURPOSE: Hypercholesterolemia is a critical problem in patients with carotid atherosclerosis. The adequacy of attention to lipid risk factors in patients with carotid stenosis awaiting carotid endarterectomy (CEA) has rarely been studied. We also assessed patient awareness of hypercholesterolemia and carotid plaque morphology. METHODS: A prospective study was conducted of 141 consecutive patients admitted electively for CEA. Each patient's medical history was taken. Plasma cholesterol concentrations were determined. Plaque histology was scored according to American Heart Association criteria and their modification. RESULTS: Of patients who were aware of their hypercholesterolemia and who were receiving treatment, 28.6% had total cholesterol levels > or =5 mmol/L. Among those patients who had been told that they had no problem with hypercholesterolemia, 32.5% had plasma cholesterol concentrations > or =5 mmol/L. Among those patients who had never had their plasma cholesterol measured, 48.4% had total cholesterol levels > or =5 mmol/L. Patients in this last group tended to have more severe types of plaque pathology than those in other groups (12.9% plaque rupture). CONCLUSIONS: Hypercholesterolemia does not seem to be well managed in patients awaiting CEA.