Outcome of moderate carotid artery stenosis in patients who are asymptomatic

PURPOSE: The incidence rate of disease progression and stroke after the diagnosis of a moderate (50% to 79%) carotid stenosis was determined by means of color-flow duplex scanning. METHODS: During a 4-year period, 344 male veterans with moderate internal carotid artery stenoses, on one or both sides, were examined at regular intervals for a mean period of 25 months. Carotid color-flow scans were obtained semiannually. Clinical follow-up was performed to determine the incidence rate of amaurosis fugax, transient ischemic attacks, nonhemispheric symptoms, and strokes. RESULTS: New neurologic symptoms developed in 75 patients (21.8%). Fifty-one (14.8%) had ipsilateral symptoms during follow-up: 18 amaurosis fugax (5.2%), 14 transient ischemic attacks (4%), 5 nonhemispheric symptoms (1.4%), and 14 strokes (4%). Twenty-four patients (6.9%) had contralateral symptoms: 20 strokes (5.8%) and 4 transient ischemic attacks (1.2%). Life-table analysis showed that the annual rate of ipsilateral neurologic events was 8.1%, and the annual rate of stroke was 2.1%. Seventy-five patients (22%) died in the follow-up period. Disease progression to 80% to 99% stenosis or occlusion occurred in 71 of 458 vessels (15.5%). The internal carotid arteries that showed evidence of disease progression had a significantly higher initial peak systolic velocity (251 vs 190 cm/s; P <.0001) and end diastolic velocity (74 vs 52 cm/s; P < 0.0001). Black patients and patients with ischemic heart disease were at a higher risk for disease progression. We could not identify any atherosclerotic risk factors that reliably predicted patients in whom future ipsilateral neurologic symptoms were more likely to develop. However, there was an increased risk of stroke associated with progression of disease. CONCLUSION: Patients who are asymptomatic and who have moderate carotid stenoses are at significant risk for neurologic symptoms and death, but have a relatively low incidence rate of ipsilateral events. The initial flow characteristics in the stenotic vessel are predictive of future disease progression, but they are not helpful in identifying patients in whom symptoms will develop.     

Pathophysiology and inflammatory aspects of plaque rupture

We describe the purification and characterisation of a thioredoxin reductase-like disulphide reductase from the ancient protozoan parasite, Giardia duodenalis. This dimeric flavoprotein contains 1 mol FAD per subunit and had an apparent subunit molecular mass of 35 kDa. The purified enzyme catalysed the NADPH-dependent (Km = 8 microM) reduction of 5,5'-dithio-bis(2-nitrobenzoic acid) to thionitrobenzoate and was unable to utilise NADH as an electron donor. The sulphydryl-active compounds, N-ethylmaleimide, sodium arsenite and Zn2+ ions, strongly inhibited the enzyme suggesting that a thiol component forms part of the active site. Purified enzyme was able to utilise a variety of substrates, including cystine and oxidised glutathione, which suggests that it is a broad-range disulphide reductase, probably accounting for the majority of thiol cycling activity in this organism. While the G. duodenalis enzyme does not require an intermediate electron transport protein, analogous to thioredoxin, for activity, we have identified a candidate carrier protein which enhances DTNB turnover six fold, therefore implying that Giardia contains a thioredoxin-like system. Physical, enzymatic and spectral properties of the G. duodenalis disulphide reductase are also consistent with it being a member of the thioredoxin reductase-class of disulphide reductases. Furthermore, the internal amino acid sequence of a tryptic peptide generated from the purified protein was highly homologous with thioredoxin reductases from other sources. This is the first report of a disulphide reductase to be purified from the anaerobic protozoa and explains the so called "glutathione-induced thiol-reductase activity' previously observed in G. duodenalis.     

Combined carotid endarterectomy and coronary artery bypass grafting in asymptomatic carotid artery stenosis

The role of combined carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG) in patients with severe asymptomatic carotid artery disease and concurrent symptomatic coronary artery disease is controversial. The objective of this report is to investigate the safety of combined CEA/CABG. The medical records of 30 patients who underwent combined CEA/CABG for coexistent asymptomatic carotid and symptomatic coronary artery occlusive disease were reviewed. All patients were scheduled for either elective or urgent myocardial revascularization due to their symptomatic coronary artery disease. Color-flow duplex scanning identified internal carotid artery stenosis of 80 to 99 per cent in 28 patients (93%) and 50 to 79 per cent in 2 patients (7%). Seventeen patients (57%) were male. The mean age was 64 +/- 10 years (range, 42-84 years). Contralateral internal carotid artery occlusion was present in four patients. Severe left main coronary artery disease was present in 12 patients (40%) and 7 patients (23%) had an ejection fraction of less than 50 per cent. There were no perioperative deaths or strokes. One patient suffered a myocardial infarction on postoperative day 1. This study demonstrates the safety of combined CEA/CABG for coexistent coronary and asymptomatic carotid disease. Using this surgical approach for critical coexistent disease may minimize the incidence of perioperative cerebrovascular complications in patients undergoing CABG.     

Concomitants of atherosclerotic carotid artery stenosis

To identify metabolic and other concomitants of a single important type of atherosclerotic cerebrovascular disease, 75 patients with angiographically and surgically proven internal carotid stenosis were compared with age and sex matched control subjects with respect to plasma cholesterol, triglycerides and glucose. They were also compared for blood pressure, cigarette smoking, evidence of ischemic heart disease, peripheral vascular disease and for a family history of these diseases. Patients with carotid stenosis had higher systolic and diastolic blood pressures and higher plasma cholesterol and triglyceride concentrations than the control groups. They had, as well, a far greater likelihood of being cigarette smokers and a greater likelihood of having diabetes mellitus and previous evidence of coronary and peripheral vascular disease. Patients with carotid stenosis were far more likely to have 2 or more of these common concomitants of atherosclerosis than were the control subjects. The data suggest that the precursors of carotid stenosis are similar to those of coronary atherosclerosis and raise the hope that modification of these factors may decrease the incidence of this highly prevalent form of cerebrovascular disease.     

Elective stenting of carotid artery stenosis in patients with severe coronary artery disease

AIMS: To evaluate the feasibility and safety of elective carotid stent implantation in patients with carotid stenoses and concomitant coronary artery disease, as an alternative to combined carotid and coronary surgery. METHODS: We treated 50 patients with >70%, stenoses in 53 carotid arteries with balloon angioplasty followed by elective stent implantation. All patients had severe coronary artery disease, and/or mitral insufficiency, aortic stenosis, rhythm disorders or generalized arteriosclerosis. In three patients the opposite carotid artery was occluded; nine patients had bilateral stenoses of which two received stents bilaterally. RESULTS: Fifty-six successful stent implantations (42 Wallstents, eight BeStents, two AVE-Microstents, one Palmaz Schatz stent, three Sito stents) were performed, reducing the baseline percent stenosis from 78 +/- 18%, to 13 +/- 11%. Complications included three transient ischaemic attacks, one minor and one major stroke. Follow-up was available for 46 patients over a mean of 10 months. Three asymptomatic restenoses and one deformation of a BeStent occurred. CONCLUSION: Our preliminary results indicate that carotid artery stenting in patients with concomitant severe coronary artery disease is feasible, safe, and may be an alternative to combined carotid and coronary surgery.     

Impaired dynamic cerebral autoregulation in carotid artery stenosis

BACKGROUND AND PURPOSE: If it could be determined whether cerebral blood flow can be maintained (autoregulated) during transient falls in arterial blood pressure, we might be able to identify patients with carotid stenosis who are at risk of stroke. However, conventional methods of determining autoregulation in such patients are invasive and/or expensive. METHODS: We used a new noninvasive method to estimate dynamic cerebral autoregulation in 27 patients with carotid stenosis and 21 age-matched normal controls. After a stepwise fall in arterial blood pressure, we determined the rate of rise of middle cerebral artery blood flow velocity compared with that of arterial blood pressure. We compared the method with a conventional method of determining cerebral hemodynamics, CO2 reactivity. RESULTS: Autoregulatory index (ARI) was significantly reduced in middle cerebral arteries ipsilateral to a stenosed/ occluded carotid artery: mean +/- SD 3.3 +/- 2.2 compared with normal controls (6.3 +/- 1.1; P < .0001) and nonstenosed carotid arteries in patients (5.9 +/- 2.1; P < .002). A subgroup of patients with severe impairment was identified. ARI returned to normal after carotid endarterectomy was performed. In a number of cases, ARI was impaired in the presence of CO2 reactivity. CONCLUSIONS: This simple technique allows identification of impaired autoregulation in patients with carotid artery disease. It may allow identification of patients at risk from transient falls of blood pressure as may occur at the onset of antihypertensive therapy and during surgery. It may allow a subgroup of patients with asymptomatic carotid stenosis who are at risk of hemodynamic stroke to be identified.     

Spontaneous rupture of the common carotid artery with pseudoaneurysm formation

A 27-year-old man presented to the ED with an expanding neck mass after a Valsalva maneuver during sexual intercourse. This patient was found to have sustained a spontaneous rupture of the common carotid artery with pseudoaneurysm formation. The defect was repaired surgically with a saphenous vein patch, and the patient recovered. We discuss the rare occurrence of spontaneous carotid artery rupture and subsequent pseudoaneurysm.     

Pseudo-tandem stenosis of the internal carotid artery

Two cases of pseudo-tandem stenosis of the internal carotid artery are presented. Proximal stenosis was produced by a large, focal atherosclerotic plaque. The severe intracranial "stenosis" was thought to be an angiographic artifact. Repeat cerebral angiography after carotid endarterectomy revealed normal intracranial arteries. The recognition of this entity is important because a decision to operate is based largely upon angiographic findings.     

How does carotid artery stenosis increase?

In 25 patients with carotid artery stenosis equal or higher than 40% colour doppler examinations were performed 105 times. The aim of this study was estimate the dynamics of progress of carotid artery stenosis. The mean time of observation was 22.5 months. In 11 (44%) patients there was no progress of stenosis, in 6 (24%) a leap progress over 30% of arterial lumen, and in 8 (32%) patients the progress of carotid artery stenosis were gradual and slow. The leap progress of carotid artery stenosis was usually caused by eruption or dissection of atherosclerotic plaque located in carotid bifurcation and this situation poses especially high risk of stroke.     

Inflammation in high-grade carotid stenosis: a possible role for macrophages and T cells in plaque destabilization

BACKGROUND AND PURPOSE: Inflammatory mechanisms have been implicated in the pathogenesis of atherosclerosis. In this study, we investigated whether the extent of inflammatory infiltration in high-grade stenoses of the internal carotid artery (ICA) correlates to clinical features of plaque destabilization. METHODS: Endarterectomy specimens from 37 consecutive patients undergoing surgery for high-grade ICA stenosis were stained immunocytochemically for macrophages (CD68) and T cells (CD3). The staining was quantified by planimetry of immunostained areas (CD68) or counting individual cells (CD3). Clinical evidence of plaque instability was provided by the preoperative assessment of recent ischemic symptoms attributable to the stenosis and of the occurrence of cerebral microembolism in transcranial Doppler ultrasound monitoring of the ipsilateral middle cerebral artery. RESULTS: The percentage of macrophage-rich areas and number of T cells per mm2 section area were larger in recently symptomatic patients than in asymptomatic patients (macrophages: 18+/-10% versus 11+/-4%, P=0.005; T cells: 71.2+/-34.4 versus 40.5+/-31.4 mm2, P=0.005). The presence of microembolism was associated with an increase in macrophage-rich areas (P=0.011). Macrophage (19+/-10% versus 9+/-3%, P=0.0009) and T cell (71.5+/-39.0 versus 46.4+/-22 mm2, P=0.045) infiltration were more pronounced in predominantly atheromatous than in fibrous plaques, but did not correlate significantly to the presence of surface ulceration or luminal thrombosis. CONCLUSIONS: Our data suggest a role of plaque-infiltrating macrophages and T cells in the clinical destabilization of high-grade ICA stenoses. Inflammatory mechanisms may be a therapeutic target in patients with symptomatic ICA disease.     

Concurrent aneurysm rupture and thrombosis of high grade internal carotid artery stenosis: report of two cases

BACKGROUND: The simultaneous presentation of aneurysmal subarachnoid hemorrhage and thrombosis of a high-grade internal carotid artery stenosis is rare, and their management raises several treatment dilemmas. METHODS: Two such patients with ruptured aneurysms are presented: one with high-grade internal carotid artery stenosis that progressed to occlusion and one with acute internal carotid artery occlusion. RESULTS: Both patients were treated with craniotomy for clipping of the ruptured aneurysm followed by carotid thromboendarterectomy. CONCLUSIONS: We advocate urgent surgical treatment of both lesions, dealing with the most symptomatic lesion first. These two cases demonstrate the importance of reestablishing blood flow in patients with an acutely thrombosed carotid artery.     

Differences in near-wall shear rate in the carotid artery within subjects are associated with different intima-media thicknesses

In the common carotid artery, reflections originating from the periphery and the flow divider may affect the shape of the flow velocity profile and, hence, near-wall shear rate (WSR) differently just before the bifurcation (location B) than 20 to 30 mm farther upstream (location A). Recent developments in ultrasound technology allow the assessment of WSR and intima-media thickness (IMT) at the same site in the carotid artery in vivo. We therefore determined WSR at locations A and B and investigated whether the differences between both sites, if any, were associated with different IMTs and different mechanical properties of the arterial wall. The effect of age on the possible differences was assessed as well. The study was performed on presumably healthy volunteers (n=53). In all individuals, IMT was larger at location B than at location A. The relative difference in IMT between both locations was not affected by age. No significant differences in diameter and distension were found between locations. Near peak systolic and near mean WSR at the posterior wall (PWSRp and MWSRp, respectively) were significantly lower at location B than at location A. The relative differences in PWSRp and MWSRp between both locations within subjects were independent of age. The velocity profiles were more blunted at location A than at location B. PWSRp and MWSRp significantly decreased and IMT significantly increased with age at both locations. IMT was negatively correlated with PWSRP and MWSRP at location B, but this correlation was not significant at location A. In summary, in the common carotid artery, the lower WSR near the bifurcation, as compared with 20 to 30 mm upstream, is associated with a larger IMT than at the more proximal site. The relative difference between both locations within subjects is independent of age.     

Is plaque formation in the common carotid artery representative for plaque formation and luminal stenosis in other atherosclerotic peripheral arteries? A post mortem study

A simple high-performance liquid chromatographic method was developed for the determination of ranitidine in human plasma. Prior to analysis, ranitidine and the internal standard (metoprolol) were extracted from alkalinized plasma samples using dichloromethane. The mobile phase was 0.05 M potassium dihydrogenphosphate-acetonitrile (88:12, v/v) adjusted to pH 6.5. Analysis was run at a flow-rate of 1.3 ml/min and at a detection wavelength of 229 nm. The method is sensitive with a detection limit of 1 ng/ml at a signal-to-noise ratio of 3:1, while the quantification limit was set at 15 ng/ml. The calibration curve was linear over a concentration range of 15-2000 ng/ml. Mean recovery value of the extraction procedure was about 90%, while the within-day and between-day coefficients of variation and percent error values of the assay method were all less than 15%.     

Anterior spinal artery syndrome associated with severe stenosis of the vertebral artery

We describe a 55-year-old man with quadriparesis and impaired pain and temperature sensation in whom T2-weighted MR images revealed a high-intensity lesion in the cord at C3-4. Angiography showed occlusion of the right vertebral artery and severe stenosis of the left vertebral artery. We concluded that the stenosis of the vertebral artery led to the anterior spinal artery syndrome and to a disturbance of consciousness.     

Comparison of isradipine and enalapril effects on regional carotid circulation in patients with hypertension with unilateral internal carotid artery stenosis

This randomized, double-blind, placebo-controlled study was aimed at detecting cerebrovascular effects of isradipine and enalapril in patients with moderate hypertension depending on the presence and grade on unilateral stenosis of internal carotid artery (ICA). We evaluated carotid vascular resistance by using Doppler analysis and regional cerebral blood flow (rCBF) by using 133Xe-clearance technique before and after a single 5-mg oral dose of isradipine, enalapril, or placebo. Their effects were randomly and consecutively tested in 73 patients with essential hypertension subdivided into three groups: without carotid occlusive lesions, with moderate (50-75%), and with severe (76-99%) unilateral asymptomatic ICA stenosis. There were no differences in age, gender, and antihypertensive effects of the drugs between these three subgroups. Three major variants of cerebrovascular drug effects were observed: absence of changes (variant I), decrease in carotid vascular resistance with increase in rCBF and elimination of side-to-side asymmetry (variant II), and increase in carotid vascular resistance with further reduction of rCBF ipsilaterally ICA stenosis, and increased side-to-side asymmetry (variant III). Frequency of variant III was significantly higher in patients with severe ICA stenosis. Enalapril produced variant I of cerebrovascular effects in most patients examined; variant III was observed only in 13% of patients with severe ICA stenosis. Isradipine produced variant I of cerebrovascular effects much less frequently than did enalapril. For this drug, variant II was most typical in patients without ICA stenosis and with moderate ICA stenosis. In 43.5% of patients with severe ICA stenosis, however, isradipine produced reduction of cerebral perfusion. Presumably the presence of ICA stenosis, especially >75%, increases the risk of cerebrovascular disorders in antihypertensive therapy. In patients with severe ICA stenosis, treatment with enalapril appears to be safer than that with isradipine.     

Asymptomatic carotid artery stenosis and stroke in patients undergoing cardiopulmonary bypass

PURPOSE: This study was undertaken to assess the natural history of carotid artery stenosis in patients undergoing cardiopulmonary bypass (CPB) at a Veterans Administration Medical Center. METHODS: Between January 1989 and August 1993, all patients undergoing CPB were offered preoperative carotid artery ultrasound screening as part of an investigative protocol. Patients were monitored in-hospital for the occurrence of perioperative neurologic deficit. RESULTS: A total of 582 patients underwent carotid artery ultrasound screening. Greater than 50% stenosis or occlusion of one or both internal carotid arteries was present in 130 patients (22%), with 80% or greater stenosis or occlusion of one or both arteries present in 70 patients (12%). In-hospital stroke or death occurred in 12 (2.1%) and 36 (6.2%) patients, respectively. Of the 12 strokes, five were global and seven were hemispheric in distribution. Of the five patients who had global events, none had evidence of carotid artery stenosis. However, of the seven patients who had hemispheric events, five had significant 50% or greater stenosis or occlusion of the internal carotid artery ipsilateral to the hemispheric stroke. Therefore the presence of carotid artery stenosis or occlusion was significantly associated with hemispheric stroke (no stenosis 0.34% vs stenosis 3.8%; p = 0.0072). Furthermore, the risk of hemispheric stroke in patients with unilateral 80% to 99% stenosis, bilateral 50% to 99% stenosis, or unilateral occlusion with contralateral 50% or greater stenosis was 5.3% (4 of 75). No strokes occurred in patients with unilateral 50% to 79% stenosis (n = 52). CONCLUSIONS: It is concluded that carotid atherosclerosis is a risk factor for hemispheric stroke in patients undergoing CPB.     

Computed tomographic angiography for the evaluation of carotid artery stenosis

BACKGROUND AND PURPOSE: No previous study has compared the reliability of carotid artery measurement provided by axial images, shaded surface display (SSD), and maximum intensity projection (MIP). METHODS: Helical CT and conventional angiography were performed prospectively in 20 patients with atherosclerotic stenosis of the internal carotid artery. Stenosis measurement was performed in a blinded fashion on angiography and CT by two independent examiners. Calcifications were segmented when they were located far enough from the vascular lumen. SSD and MIP were systematically performed for each carotid bifurcation. We measured stenosis using conventional angiography as standard and the different CT reconstructions (axial images, SSD, and MIP) by comparing the stenosis diameter at its narrowest point to the normal internal carotid artery. The degree of stenosis was classified into six groups: no stenosis, mild stenosis (< 30%), moderate stenosis (30% to 70%), severe stenosis (> 70%), near occlusion, and occlusion (100%). No measurement was made in cases of normal artery, near occlusion, and occlusion. RESULTS: Correlations between angiography and the three types of reconstruction were very good. Axial sections correctly classified the carotid arteries in 95% of cases. In 10 carotid arteries, stenosis was not assessable by SSD and MIP because of calcifications. In the remaining carotid arteries, MIP correctly classified the degree of stenosis in 96% of cases, whereas SSD misclassified 21% of cases. CONCLUSIONS: Our study showed that axial images provide a reliable evaluation of carotid artery stenosis. Calcifications are limiting factors in SSD or MIP. When atherosclerotic plaques are not calcified, MIP reconstructions provide a more reliable measurement of the vascular lumen than SSD.