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A possible association between body iron stores, measured as serum ferritin, and carotid arterial intima-media thickening was investigated in the Atherosclerosis Risk in Communities Study during 1990-1992 using a matched case-control design. For a 143-micrograms/liter greater serum ferritin concentration (the interquartile range), the odds ratio for cases with carotid intima-media thickening versus controls was 1.12 (95% confidence interval 0.97-1.30). However, there was no association (odds ratio = 1.00) after adjusting for major cardiovascular risk factors. This analysis of carotid arterial intima-media thickening, a measure of early atherosclerosis, in relation to serum ferritin does not support the hypothesis that increased body iron stores increase the risk of atherosclerotic cardiovascular disease.

Background: Although much has been written in recent years about the relation between alcohol and atherosclerotic disease, controversy exists as to whether and how alcohol exerts an effect on atherosclerosis in different sites., Methods and Results: We tested the hypothesis that alcohol consumption is associated inversely with carotid atherosclerosis in a population sample of 45- to 64-year-old men and women who participated in the Atherosclerosis Risk in Communities (ARIC) Study and were free of cardiovascular disease at a baseline examination in 1987 to 1989. B-mode ultrasonography was used to determine carotid artery intimal-medial wall thickness and distensibility as indices of the degree of atherosclerosis. The level of alcohol consumption in the ARIC sample was generally low. Age-adjusted mean values of alcohol consumed (grams per week) were 72.0 for white and 74.3 for nonwhite men and 24.8 for white and 11.2 for nonwhite women. After adjustments for age, artery depth, education, body mass index, sport index, cigarette-years of smoking, low-density lipoprotein cholesterol, and diabetes mellitus, there was no significant cross-sectional association of reported current alcohol intake with either carotid artery wall thickness (among white and nonwhite men and nonwhite women) or distensibility (in any of the four sex-race groups). Among white women, the adjusted mean value of carotid artery wall thickness tended to be higher in light to moderate drinkers than in never or rare drinkers, but the difference across drinking status categories was of borderline statistical significance (P = .04) and may be of little biological importance., Conclusions: The ARIC Study found no material cross-sectional association between current alcohol intake and carotid atherosclerosis but provides an opportunity in the future to study atherosclerosis progression and incident events in relation to alcohol consumption in a large population sample of men and women.

Background and Purpose: To determine the effect of a lipid-lowering agent and/or a low-dose antithrombotic agent on the progression of early-stage carotid atherosclerosis, noninvasive B-mode ultrasound was used to measure intimal-medial thickness in asymptomatic individuals with moderately elevated lipids as part of the ongoing multicenter Asymptomatic Carotid Artery Plaque Study., Methods: Uniform ultrasonic scanning and reading protocols were implemented to obtain maximum intimal-medial thickness measurements in 12 standard segments in patients having a small to moderate wall thickness (1.5-3.5 mm) in at least one of the carotid arteries. Paired B-mode image recordings on 858 patients, performed 1 month apart and read at a core laboratory (each pair by the same reader), determined both within-sonographer (W, n = 405) and between-sonographer (B, n = 453) reproducibility., Results: The primary end point (mean +/- SD), defined in each individual as the mean value of the 12 maximum intimal-medial thickness measurements, was 1.31 +/- 0.21 mm (W) and 1.32 +/- 0.22 (B) at the time of the second examination. The mean difference in the primary end point (exam 2-exam 1) was -0.01 +/- 0.13 mm (W) and 0.00 +/- 0.15 mm (B). The Pearson correlation coefficients were 0.79 (W) and 0.75 (B). In 90% of the patients, the absolute difference in the primary end point was less than 0.22 mm (W) and less than 0.24 mm (B). Variability of the secondary end point, defined as the single largest intimal-medial thickness measurement in a patient, was between three and four times larger than the variability for the primary end point. Differences in sonographer performance between clinical centers were very small., Conclusions: The results demonstrate that standardized noninvasive ultrasonic techniques yield highly reproducible measures of carotid intimal-medial thickness, which can serve as a measure of carotid atherosclerosis in clinical trials that monitor small rates of lesion progression.

Routine follow-up of patients after carotid endarterectomy with duplex scanning is commonly practiced, yet the clinical significance of identifying those with asymptomatic restenosis is unclear. To address this issue we reviewed 120 consecutive patients who underwent 143 carotid endarterectomies from August 1983 to December 1988. One hundred one patients (118 operations) were available for clinical follow-up, and the overall incidence of recurrent symptoms was 6% (6/101). Sixty-three of these patients (78 carotid endarterectomies) had postoperative duplex examination. Two had evidence of residual disease from the time of surgery and were not included in further analysis. Significant recurrent stenosis (greater than 50% diameter reduction) developed in 14 of the remaining 76 arteries (18.2%). Twelve of 14 stenoses remained asymptomatic during follow-up from 18 to 72 months (mean 47.0 months) and did not undergo reoperation. Recurrent ipsilateral hemispheric symptoms developed in two patients with restenosis (14.3%). Four of the 62 arteries without significant recurrent stenosis developed ipsilateral symptoms (6.5%), but none required reoperation during follow-up from 1 to 71 months (mean 31.6 months). Life-table analysis showed no increased risk of transient ischemic attack, stroke, or death in patients with restenosis. This study supports regular clinical follow-up after carotid endarterectomy with emphasis on patient education in the recognition of symptoms. Although duplex scanning may be useful to follow known contralateral asymptomatic disease or evaluate those with recurrent symptoms, its routine use to identify patients with asymptomatic restenosis after carotid endarterectomy may be unnecessary.

Continuous-wave ultrasonic Doppler recordings made at the carotid bifurcation have been processed by spectrum analysis and off-line microprocessor software. Data reduction algorithms were defined and tested prior to incorporation in an integrated, hard-wired device. Subsequent analysis of waveforms in real-time provided measures of peak and mode frequencies and degree of spectral broadening. Correlation of results with 123 angiographically visualized internal carotid arteries showed that peak and mode frequencies generally increased with degree of stenosis while the systolic window decreased. Ratios of peak and mode frequencies in the proximal to the distal internal carotid artery and the systolic window at the distal internal carotid artery were retrospectively found to have diagnostic value with a combination of these three parameters providing the best overall accuracy.

A prospective study compared the sensitivity, specificity, and predictive value of indirect periorbital Doppler screening and direct carotid Doppler interrogation using real-time sound spectrum analysis to detect operable extracranial carotid occlusive disease. The results of noninvasive studies were compared with independently assessed contrast arteriograms of carotid arteries of patients studied for symptomatic cerebrovascular disease. Periorbital Doppler ultrasound was insensitive to carotid stenosis of less than 75% and did not distinguish operable stenosis from inoperable occlusion of the internal carotid artery. Carotid Doppler spectrum analysis was sensitive to 98% of hemodynamically significant disease and correctly discriminated 77% of carotid occlusions, 96% of stenoses larger than 50%, and 70% of stenoses of less than 50%. The predictive value for direct carotid interrogation in identifying carotid occlusion or operable stenosis was 94% and 86%, respectively. Real-time spectrum analysis of direct carotid Doppler signals substantially improves the diagnostic accuracy of noninvasive identification of operable carotid artery disease.

This article reviews the published experience supporting or refuting the value of prophylactic endarterectomy in patients with asymptomatic carotid disease who are candidates for major cardiovascular operations. Reports of 1,483 patients subjected to staged or concomitant carotid endarterectomy and coronary artery bypass grafting reveal a perioperative stroke rate of 2.9%. Timing of carotid endarterectomy did not influence stroke rate, but staged procedures were associated with a significantly greater incidence of perioperative myocardial infarction and death. Studies of patients undergoing major cardiovascular surgical operations without prophylactic carotid endarterectomy reported a perioperative stroke rate of 2.7%, which is not significantly different from that of patients undergoing prophylactic carotid endarterectomy. However, the author's prospective study of such patients showed a significant incidence of late postoperative neurologic deficits, which are usually transient ischemic attacks. There is no evidence to justify routine prophylactic carotid endarterectomy of asymptomatic carotid disease before major cardiovascular operations. Patients not undergoing endarterectomy, however, should be given careful postoperative follow-up, because transient ischemic attacks may occur that require surgical intervention.

This prospective study used non-invasive techniques to screen for asymptomatic carotid occlusive disease in 314 patients who were to have coronary or peripheral arterial reconstruction. Hemodynamically significant carotid obstruction (greater than or equal to 50% stenosis or occlusion) was present in 54 arteries of 41 patients (13.1%), but only one-third of these lesions were accompanied by a cervical bruit. Among 48 carotid arteries where a bruit was heard, only 18 (37.5%) were associated with significant obstruction demonstrated by non-invasive screening. No prophylactic carotid endarterectomies were performed. There was only one perioperative TIA and one non-fatal stroke, neither of which was related to detectable carotid obstruction. In patients with peripheral vascular disease and detectable carotid obstruction or bruit, the perioperative mortality was higher than in patients without carotid obstruction or bruit (15.0% and 18.2 vs 3.1% and 2.1%, respectively). The deaths were primarily due to myocardial infarction. This study suggests that asymptomatic carotid occlusive disease, while common in patients with other cardiovascular disease, does not necessarily predispose to perioperative stroke and thus does not necessitate prophylactic carotid endarterectomy prior to indicated coronary or peripheral vascular reconstruction.

Doppler ultrasonic assessment of extracranial carotid occlusive disease has been modified to decrease the incidence of false positive and negative diagnoses. The technique, which assessed directional flow in the frontal artery and the influence of sequential compression of each temporal, infraorbital, facial and common carotid artery, was performed on 152 vessels visualized by contrast arteriography. Presence or absence of significant (greater than 50%) stenosis or occlusion of the internal carotid artery was identified correctly in 150 vessels (98.7%). Inasmuch as the classic temporal artery compression test only detected 39 of the 61 abnormal Doppler studies (64%), the more complete examination is recommended for screening patients for significant carotid artery obstruction.

Pulsed ultrasonic images of the carotid bifurcation in 82 vessels of 43 patients were compared independently with contrast arteriograms for stenosis (by percentage quartiles) or occlusion of the internal carotid artery. All 14 occluded vessels were identified correctly by ultrasound but were visualized on repeat examination. Estimation of percentage stenosis on ultrasonic images agreed with the quartile determination by contrast arteriography in 35 of 68 (51 percent) vessels and was within one quartile of correct interpretation in 48 of 68 (71 percent). The interpretative error of grading stenosis of ultrasonic images was due to vascular wall calcification which inhibited ultrasound transmission. This limitation was overcome by sound spectral (sonographic) analysis of distal internal carotid flow velocity which allowed estimation of stenosis within one quartile of that determined by contrast arteriography in 46 of 47 (98 percent) vessels.

In a previous prospective study of 449 patients undergoing coronary or peripheral arterial reconstruction, 85 patients had preoperative evidence of asymptomatic bruit and/or greater than 50% carotid obstruction by routine Doppler screening. No patient had prophylactic carotid endarterectomy. This article reviews the late postoperative outcome (2 to 61 months, mean 35 months) of 67 patients with asymptomatic carotid disease who survived operation without perioperative deficit. Eleven patients died (16%) including four of myocardial infarction and two of stroke. Neurologic deficits occurred in the late postoperative period in 22 patients (32.8%) after an average interval of 31 months, including transient ischemic attacks in 15 patients (22.4%); only four of these 15 were appropriate to the side of carotid disease documented preoperatively. Seven patients (10.4%) suffered stroke, only three (4.5%) of which were in the territory of carotid disease detected preoperatively. The cumulative rate of carotid disease progression was 34%, including three patients who suffered carotid occlusion. Two of the latter had the only fatal strokes. This study suggests that patients with asymptomatic carotid disease, although not at significant risk of perioperative stroke, require careful follow-up for late postoperative neurologic deficits, the majority of which (68%) are transient ischemic attacks.

Indirect periorbital screening techniques may detect obstruction of the extracranial internal carotid artery, but they do not distinguish operable stenosis from inoperable occlusion. In an attempt to overcome this limitation, direct interrogation of carotid artery flow velocity by Doppler ultrasound was added to periorbital screening of 97 arteries in 53 patients. Analysis of results suggests that this assessment can improve diagnostic accuracy and distinguish stenosis from occlusion of the internal carotid arteries in stroke-prone patients.

A directional Doppler ultrasound cerebrovascular examination was compared with angiographical findings of 152 internal carotid arteries. The Doppler examination was abnormal in 36 of 38 (95%) arteries with occlusion or stenosis greater than 75%. Of 63 arteries with lesser degrees of stenosis, the Doppler examination identified only four. There were no false-positive Doppler examinations. If the decision to perform angiography had been predicated exclusively on the presence of abnormal Doppler findings, 61 of 101 (60%) carotid lesions of potential clinical significance would have been overlooked. While the Doppler ultrasound cerebrovascular examinations is the most useful noninvasive technique available for the evaluation of certain specific categories of patients with cerebrovascular disease, the technique is based on hemodynamic alterations of pressure and flow, and cannot be expected to identify the relatively large number of non-hemodynamically significant carotid lesions that are still clinically significant as sources of emboli. This paper illustrates that in the routine evaluation of patients with symptomatic cerebrovascular disease, the Doppler examination should not play a part in the decision to proceed with angiography.

The cerebrovascular Doppler examination indicated a significant stenosis in only 19 of 53 patients with non-hemispheric TIA'S. There were no false negative or false positive examinations. Fourteen of 19 patients with an abnormal examination and 23 of 31 patients with a normal examination became asymptomatic after a carotid endarterectomy. Eleven patients were improved and two were unchanged. Therefore the cerebrovascular Doppler examination can not be used to predict therapeutic success or failure of carotid endarterectomy for non-hemispheric TIA's.

A sterile Doppler probe was used for intraoperative monitoring of the integrity of carotid endarterectomy of 125 vessels of 107 patients. Our objective was to reduce the contribution of residual carotid lesions to recurrent stenosis, which was evaluated by Doppler spectrum analysis in the early (less than 3 months, 66 arteries) and late (3-77 months, mean 32 months, 47 arteries) postoperative period. Intraoperative Doppler monitoring detected residual occlusion in six (4.8%) external carotid arteries and stenosis in ten (8.0%) internal carotid arteries permitting selected arteriography and correction of all significant lesions. Follow-up revealed one (1.5%) asymptomatic common carotid occlusion at 6 weeks and three (6.4%) asymptomatic internal carotid stenoses at 6, 10 and 25 months after operation. When compared to previous published experience, these results suggest that intraoperative correction of residual carotid obstruction detected by Doppler ultrasound may reduce the incidence of postoperative "recurrent" carotid stenosis.

Direct interrogation of the common, internal, and external carotid arteries with a bidirectional Doppler detector was performed on 199 vessels in 101 patients. Audible interpretations of normal, disturbed (stenotic), or absent (occluded) flow signals were made by vascular technologists and the results were compared with independently assessed carotid arteriograms. The sensitivity in detecting severe (greater than or equal to 50%) stenosis or occlusion was 9.2%, with correct differentiation of these two conditions in 84% of vessels. Nonobstructive (less than 50%) stenoses were detected in 30% of cases. The specificity in identifying normal carotid arteries was 91%. The predictive values of normal, abnormal, and absent flow signals were 95%, 90%, and 90%, respectively. Direct carotid Doppler signal analysis is more accurate than indirect periorbital Doppler screening in defining carotid stenosis or occlusion.

Prospective screening of 449 patients undergoing coronary or peripheral arterial revascularization detected asymptomatic cervical bruits in 44 patients (9.8%) and carotid obstruction by Doppler ultrasound in 63 individuals (14.0%). There was poor correlation between cervical bruit and carotid obstsruction. No patient underwent prophylactic casrotid endarterectomy. Three patients had transient ischemic attacks (TIAs), and five had nonfatal strokes perioperatively, only one of which was in the territory appropriate to carotid obstruction. Of 72 surviving patients with asymptomatic carotid disease, 10 (13.9%) had TIAs and one (1.4%) died of stroke during a 2-year follow-up, during which time only two (0.8%) of 254 patients without carotid disease reported symptoms of TIAs. Patients with asymptomatic carotid disease had a significantly higher incidence of perioperative and late deaths (10.6% and 9.2%, respectively), usually of myocardial infarction, as compared to patients without carotid disease (0.3% and 0.8%, respectively, P less than 0.001). Asymp-tomatic carotid disease, although correlating poorly with perioperative stroke in patients undergoing cardiovascular operations, identifies patients at risk of late neurologic events and peroperative or late deaths from myocardial infarction. We do not recommend prophylactic carotid endarterectomy but favor operative intervention if patients develop TIAs during a period of careful follow-up .