Mannheim carotid intima-media thickness and plaque consensus (2004-2006-2011). An update on behalf of the advisory board of the 3rd, 4th and 5th watching the risk symposia, at the 13th, 15th and 20th European Stroke Conferences, Mannheim, Germany, 2004, Brussels, Belgium, 2006, and Hamburg, Germany, 2011.

Intima-media thickness (IMT) provides a surrogate end point of cardiovascular outcomes in clinical trials evaluating the efficacy of cardiovascular risk factor modification. Carotid artery plaque further adds to the cardiovascular risk assessment. It is defined as a focal structure that encroaches into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value or demonstrates a thickness >1.5 mm as measured from the media-adventitia interface to the intima-lumen interface. The scientific basis for use of IMT in clinical trials and practice includes ultrasound physics, technical and disease-related principles as well as best practice on the performance, interpretation and documentation of study results. Comparison of IMT results obtained from epidemiological and interventional studies around the world relies on harmonization on approaches to carotid image acquisition and analysis. This updated consensus document delineates further criteria to distinguish early atherosclerotic plaque formation from thickening of IMT. Standardized methods will foster homogenous data collection and analysis, improve the power of randomized clinical trials incorporating IMT and plaque measurements and facilitate the merging of large databases for meta-analyses. IMT results are applied to individual patients as an integrated assessment of cardiovascular risk factors. However, this document recommends against serial monitoring in individual patients.

Carotid plaque morphology improves stroke risk prediction: usefulness of a new ultrasonographic score.

Carotid thickening and plaque detected by B-mode imaging ultrasound are useful to improve the ischemic risk evaluation in asymptomatic subjects over and beyond the traditional cardiovascular risk factors. Some plaque's echographic parameters help describing the vascular risk. We hypothesized that the stenosis degree, plaque surface irregularity, echolucency and texture, compounded in a Total Plaque Risk Score (TPRS), are predictors of the ischemic events in the San Daniele study, a general population-based study of 1,348 subjects followed for 12 years in average. In the 171 subjects with at least one plaque at baseline, high TPRS was the most powerful independent predictor of cerebrovascular events, which occurred in 115 subjects. Addition of plaque characteristics significantly increased the area under the ROC curve (0.90 vs. 0.88, p = 0.04) versus the Framingham risk score alone. The TPRS is a potential new tool to improve the stroke risk prediction.

Chlamydia pneumoniae seropositivity in aetiological subtypes of brain infarction and carotid atherosclerosis: a case control study.

BACKGROUND AND OBJECTIVE: Many patients with brain infarction (BI) lack traditional risk factors, suggesting that other factors (including infectious agents) might contribute to stroke risk. We investigated Chlamydia pneumoniae infection in a large cohort of patients with BI according to aetiological subtypes and carotid atherosclerosis. METHODS: We measured serum IgG and IgA to C. pneumoniae by microimmunofluorescence in 483 BI cases and 483 controls matched for age, sex and centre. IgG > or = 1/32 and IgA > or = 1/24 were considered positive. Cases with BI proven by magnetic resonance imaging were consecutively recruited and were classified into aetiological subtypes. Carotid atherosclerosis (intima-media thickness, plaques, stenosis) was evaluated by duplex ultrasonography in all subjects following the same method and with central reading. RESULTS: C. pneumoniae IgG seropositivity was not associated with BI (adjusted odds ratio (OR) 1.10, 95% confidence interval (CI) 0.80-1.51) and did not increase the risk of any aetiological subtype. Overall, C. pneumoniae IgA was not associated with BI (adjusted OR 1.54, 95% CI 0.84-2.81), but there was a significant interaction with hypertension. IgA seropositivity increased the BI risk in patients without hypertension (adjusted OR 2.79, 95% CI 1.15 to 6.74). When stratifying BI into subtypes, IgA seropositivity increased the risk of BI of unknown cause, but without significant heterogeneity. There was neither association with atherothrombotic, lacunar and cardioembolic BI nor with carotid intima-media thickness, carotid plaques or stenosis. CONCLUSIONS: We found no evidence that C. pneumoniae seropositivity is associated with carotid atherosclerosis and BI, regardless of aetiological subtype; but it might be associated with an increased risk of BI in normotensive patients.

Common carotid artery intima-media thickness and brain infarction : the Etude du Profil Génétique de l'Infarctus Cérébral (GENIC) case-control study. The GENIC Investigators.

BACKGROUND-The use of intima-media thickness (IMT) as an outcome measure in observational studies and intervention trials relies on the view that it reflects early stages of atherosclerosis and cardiovascular risk. There is little knowledge concerning the relation between IMT and brain infarction (BI). METHODS AND RESULTS-We investigated the relation of IMT with BI and its subtypes in 470 cases and 463 controls. Cases with BI proven by MRI were consecutively recruited and classified into subtypes by cause of BI. Controls were recruited among individuals hospitalized at the same institutions and matched for age, sex, and center. IMT was measured at the far wall of both common carotid arteries (CCA) using an automatic detection system. Adventitia-to-adventitia diameters and CCA-IMT were measured on transverse views; lumen diameter was computed using these measures. Mean (+/-SEM) CCA-IMT was higher in cases (0.797+/-0.006 mm) than in controls (0.735+/-0.006 mm; P<0. 0001). This difference remained after adjustment for lumen diameter and when analyses were restricted to subjects free of previous cardiovascular or cerebrovascular history. The difference in CCA-IMT between cases and controls was significant in the main subtypes. The risk of BI increased continuously with increasing CCA-IMT. The odds ratio per SD increase (0.150 mm) was 1.82 (95% confidence interval, 1.54 to 2.15); adjustment for cardiovascular risk factors slightly attenuated this relation (odds ratio, 1.73; 95% confidence interval, 1.45 to 2.07). CONCLUSIONS-An increased CCA-IMT was associated with BI, both overall and in the main subtypes. An increased IMT may help select patients at high risk for BI.

Sustained anxiety and 4-year progression of carotid atherosclerosis.

Several studies have shown that anxiety disorders are associated with a higher risk of coronary artery disease. However, the relationship between anxiety disorders and atherosclerosis has been studied to a lesser extent. The goal of this study was to examine whether high and stable trait anxiety was associated with the progression of atherosclerosis. The study group consisted of 726 subjects (297 men and 429 women), aged 59 to 71 years, recruited from the electoral rolls of the city of Nantes. The subjects had no history of coronary artery disease at baseline evaluation and or at the 2-year follow-up. Two follow-up examinations were conducted 2 and 4 years after the baseline evaluation. Trait anxiety was evaluated by means of the French translation of the Spielberger Inventory (a 20-item trait inventory, form X-2). The "sustained anxiety" group consisted of men and women with the highest Spielberger Inventory scores at baseline and at the 2-year follow-up examination. Each ultrasound examination included measurement of intima-media thickness and the sites of plaque in the extracranial carotid arteries. Men with sustained anxiety showed a higher 4-year increase of common carotid intima-media thickness than did men without sustained anxiety (adjusted means 0.08 versus 0.04 mm, respectively; P=0.05) and a higher risk of 4-year plaque occurrence (adjusted OR 3.5, 95% CI 1.4 to 8.5). Among women, sustained anxiety was associated with a higher 4-year increase of common carotid intima-media thickness (0.07 versus 0.04 for women with versus women without sustained anxiety, respectively; P=0.07). These results suggest that chronically high levels of anxiety may contribute to accelerating the evolution of carotid atherosclerosis.

Association between peak expiratory flow and the development of carotid atherosclerotic plaques.

BACKGROUND: Numerous population-based studies have suggested that impaired lung function is associated with subsequent coronary heart diseases-related mortality and cardiovascular disease-related mortality. The relative contribution of atherosclerosis in these associations is unknown. OBJECTIVE: To examine the association of peak expiratory flow (PEF) with the occurrence during 4 years of atherosclerotic plaques in the extracranial carotid arteries in a sample of 656 subjects (aged 59-71 years) free of coronary heart disease and stroke at baseline. METHODS: Peak expiratory flow was measured at the baseline examination. Peak expiratory flow values relative to the predicted values (relative PEF values) were calculated, predicted values being obtained from previously published sex-specific regression equations of PEF on age and height. A carotid B-mode ultrasonographic examination was performed at baseline and 2 and 4 years later. The occurrence of carotid plaques during follow-up was defined as the appearance of 1 plaque (or more) in previously normal carotid segments and/or the appearance of new plaques in the carotid segments that previously had plaques. RESULTS: The proportion of subjects who experienced an occurrence of carotid atherosclerotic plaques during follow-up was 16.8% (110/656). The unadjusted odds ratios from the highest to the lowest quintiles of relative PEF values were 1.00, 1.07 (95% confidence interval [CI], 0.69-2.79), 1.08 (95% CI, 0.52-2.24), 1.38 (95% CI, 0.69-2.79), and 3.07 (95% CI, 1.62-5.85) (P<.001 for trend). Adjustment for major known cardiovascular risk factors did not markedly change the results, and the multivariate-adjusted odds ratio of carotid plaque occurrence in subjects with the lowest quintile of PEF compared with those with the highest quintile remained highly significant (odds ratio, 2.84; 95% CI, 1.45-5.71) (P =.002). Particularly in all smoking categories, carotid plaque occurrence was higher in subjects with the lowest relative PEF values. In never smokers, the multivariate-adjusted odds ratio of carotid plaque occurrence in subjects with the lowest quintile of PEF compared with those with the highest quintile was 2.80 (95% CI, 1.14-6.88). CONCLUSIONS: Reduced lung function predicts the development of carotid atherosclerosis in elderly subjects. The nature of these associations remains largely unknown and merits further investigations. Nevertheless, assessment of lung function, which is simple and inexpensive, could help identify a population at high risk of atherosclerosis development and coronary heart disease.

Is patent foramen ovale a family trait? A transcranial Doppler sonographic study.

BACKGROUND AND PURPOSE: Patent foramen ovale (PFO) is a frequent finding in young patients with stroke. The aim of this study was to assess whether PFO is a family trait. METHODS: Sixty-two consecutive patients younger than 60 years of age with ischemic stroke and 62 age and gender-matched control siblings were examined by means of contrast transcranial Doppler (TCD) of the middle cerebral artery, using a standardized protocol. The reliability of TCD examination in our laboratory was assessed against transesophageal echocardiography (TEE). All TCD recordings were reviewed by a blinded experienced observer from another center. Disagreements between readers were resolved by unblinded consensus review. RESULTS: Siblings of patients with PFO had a significantly higher prevalence of PFO than had siblings of patients without PFO (61.5% versus 30.6%; OR 3.64 [1.3 to 10.5]; P=0.015). The kappa statistics indicated that agreement of pairs (patients/control siblings) was not due to chance. The strength of the association was sex dependent. In women pairs, prevalence of a PFO was 76.5% in siblings of patients with PFO and 25% in siblings of patients without PFO, giving an OR of 9.8 (95% CI 2 to 47.9; P<0.01). In contrast, in men, no significant difference was observed in the prevalence of PFO between siblings of patients with or without PFO (respectively 33.3% and 35%), giving an OR of 0.9 (95% CI 0.2 to 4.9; P=0.9). CONCLUSIONS: This study suggests that, in women, PFO is a family trait.

Combined effects of lipid peroxidation and antioxidant status on carotid atherosclerosis in a population aged 59-71 y: The EVA Study. Etude sur le Vieillisement Artériel.

There are few epidemiologic studies of the effects of lipid peroxidation and antioxidant status on atherosclerosis. The relation of lipid peroxidation evaluated by thiobarbituric acid-reactive substances (TBARS) and biological markers of antioxidant status to ultrasonographically assessed carotid atherosclerosis was examined from baseline data of a longitudinal study on cognitive and vascular aging (Etude sur le Vieillisement Artériel, the EVA Study). The study sample was composed of 1187 mean and women aged 59-71 y without any history of coronary artery disease or stroke. Ultrasound examination included measurements of intima-media thickness (IMT) on the common carotid arteries (CCAs) and at the site of plaques. After adjustment for conventional cardiovascular risk factors, erythrocyte vitamin E was significantly and negatively associated with CCA-IMT in both men and women whereas plasma selenium and carotenoids were not. No association was found between TBARS and CCA-IMT in either sex. However, TBARS were significantly higher in men with carotid plaques than in those without. This association was strengthened in men with concentrations of erythrocyte vitamin E, plasma selenium, and carotenoids below the lowest quartile. Our findings give some epidemiologic support to the hypothesis that lipid peroxidation and low antioxidant status are involved in the early phases of atherosclerosis.

Ischemic optic neuropathy associated with internal carotid artery dissection.

BACKGROUND: Ischemic optic neuropathy (ION) is an infarction of the anterior or, less frequently, posterior part of the optic nerve, usually due to a disease of small arteries supplying the optic nerve. Carotid stenosis or occlusions are rare causes, and among them, carotid dissections have been so far reported in only 5 cases. METHODS: We describe 4 patients with ION (2 anterior and 2 posterior) due to internal carotid artery dissection of a consecutive series of 110 patients with internal carotid artery dissection (3.6%). RESULTS: None of the patients had signs of central retinal artery occlusion or ischemic ocular syndrome. Ischemic optic neuropathy occurred after a mean of 5.3 days (range, 3-8 days) following the first symptom, which was headache in 1 patient, transient monocular blindness in 2, and hemispheric transient ischemic attack in 1. One patient had associated Homer syndrome, and 2 had severe ipsilateral headache and orbital pain. None of the patients developed a cerebral infarction. These features differ from those observed in "classic" nonarteritic anterior ION and might therefore point to carotid dissection. CONCLUSION: Ischemic optic neuropathy may occur as an early sign of carotid dissection: young age, previous transient monocular blindness, an association with pain, Horner syndrome, or hemispheric transient ischemic attacks are suggestive of this cause and should prompt confirmatory investigations.

Arterial wall properties in carotid artery dissection: an ultrasound study.

BACKGROUND: Cervical artery dissection is often attributed to an underlying arteriopathy related to a generalized extracellular matrix defect. OBJECTIVE: The authors compared the hemodynamic and morphologic properties of the carotid artery, as assessed noninvasively by ultrasonography, in patients with spontaneous internal carotid artery dissection (ICAD) and control subjects. METHOD: Twenty-six patients who experienced ICAD more than 6 months before evaluation were compared with 26 controls matched for age, sex, and height. Cases and controls had ultrasound measurement of common carotid artery diameter and diameter change during the cardiac cycle, bulbar and suprabulbar internal carotid artery diameters, and common carotid artery intima-media thickness. The unaffected carotid artery in cases was compared with the carotid artery of the same side in controls. RESULTS: Common carotid artery relative diameter change was significantly higher in cases than controls, whereas other measurements were not significantly different between the groups. In multivariate analyses, the highest tertile of common carotid artery relative diameter change was associated with the risk of ICAD (OR, 10.0; 95% CI, 1.8 to 54.2; p = 0.002) CONCLUSION: An underlying arteriopathy, presumably related to an extracellular matrix defect, may be present in patients with spontaneous ICAD.

Ophthalmologic manifestations of internal carotid artery dissection.

PURPOSE: To report the ophthalmologic symptoms and signs associated with extracranial internal carotid artery dissection. METHODS: One hundred forty-six consecutive patients with extracranial internal carotid artery dissection were evaluted; 29 were studied retrospectively from 1972 to 1984 and 117 prospectively from 1985 to 1997. RESULTS: Sixty-two percent of patients (91/146) with extracranial internal carotid artery dissection had ophthalmologic symptoms or signs that were the presenting symptoms or signs of dissection in 52% (76/146). Forty-four percent (65/146) had painful Horner syndrome, which remained isolated in half the cases (32/65). Twenty-eight percent (41/146) had transient monocular visual loss, which was painful in 31 cases, associated with Horner syndrome in 13 cases, and described as "scintillations" or "flashing lights"-often related to postural changes or exposure to bright lights-suggesting acute choroidal hypoperfusion in 23 cases. Four patients had ischemic optic neuropathy; one had diplopia. Among the 76 patients with ophthalmologic symptoms or signs as the presenting features of carotid dissection, a nonreversible ocular or hemispheric stroke later occurred in 27, within a mean of 6.2 days (range, 1 hour to 31 days). Eighteen patients had a stroke within the first week after the onset of neuro-ophthalmic symptoms and signs, and 24 had a stroke within the first 2 weeks. CONCLUSION: Ophthalmologic symptoms or signs are frequently associated with and are often the presenting features in internal carotid artery dissection. Painful Horner syndrome or transient monocular visual loss should prompt investigations to diagnose carotid artery dissection and begin early treatment to prevent a devastating ocular or hemispheric stroke.

[Dissecting aneurysm of the extracranial vertebral arteries and pregnancy]. / Anévrysme disséquant des artères vertébrales extracraniennes et grossesse.

A 32-year-old woman was at the end of her first and-until then normal-pregnancy, when she abruptly experienced a severe neck pain. Delivery was provoked two days later but a week after she suddenly developed a left lateral medullary syndrome. Angiography disclosed a severe diffuse and irregular narrowing of both vertebral arteries in their second and third segments, typical of dissecting aneurysm. The patient was treated with heparin and made a partial recovery. A second angiography nine months later showed a normal left vertebral artery while the right one was probably occluded.

[The A.I.C.L.A. controlled cooperative trial. Secondary prevention of cerebral ischemic accidents due to atherosclerosis by aspirin and dipyridamole. 3: Results]. / Essai coopératif contrôle "A.I.C.L.A.". Prévention secondaire des accidents ischémiques cérébraux liés à l'athérosclérose par l'aspirine et le dipyridamole. 3e partie: Résultats.

As decided in the protocol, the AICLA study ended when all the 604 patients had completed a follow up of three years. Adhesion to the protocol and drug compliance were excellent. Side effects, particularly peptic ulcers and bleedings of various origins were more frequent in the 2 treatment groups containing aspirin. The number of fatal and non fatal cerebral infarction was 31 in the P group, 17 in the ASA group, and 18 in the ASA + D group. Taking into account the duration of follow up for each patient, these figures correspond to cummulate rates of 18 p. 100 in the P group and 10.5 p. 100 in the 2 others. Analysis with the Mantel Method showed: 1 - a difference at the 6 p. 100 level between the 3 groups and between P an AD; 2 - A difference at the 5 p. 100 level between P and A; 3 - No difference between A and AD; 4 - A difference at the 2 p. 100 level between the P group and the two treated groups taken together. Among other diseases occurring during the trial, the only significant difference concerned myocardial infarction, less frequent in the 2 treated groups (p less than 0.05). Subgroup analysis failed to show a significant sex difference in the efficacy of aspirin. It is concluded that, in patients such as those defined in the protocol, Aspirin (1 g) has a significant beneficial effect in the secondary prevention of atherothrombotic cerebral infarction.

[Controlled cooperative trial. Secondary prevention of atherosclerosis-related cerebral ischemic accidents by aspirin dipyridamole. 2: Description of subjects at the beginning of the trial]. / Essai coopératif contrôlé "A.I.C.L.A." Prévention secondaire des accidents ischémiques cérébraux liés à l'athérosclérose par l'aspirine et le dipyridamole. 2e partie: Description des sujets à l'entrée dans l'essai.

This paper is the second devoted to the controlled trial "A.I.C.L.A." comparing aspirin, aspirin + dipyridamole and placebo in the secondary prevention of athero-thrombotic cerebral ischaemic events. It presents the description and distribution of baseline characteristics at entry. Six hundred and four patients (men: 70 p. 100, mean age : 63) were entered. Risk factors were distributed as follows: arterial hypertension: 63 p. 100, Diabetes: 24 p. 100, High blood lipids: 26 p. 100, high uric acid: 20 p. 100, hematocrit greater than 46 p. 100: 34 p. 100, cigarette smoking: 64 p. 100, angina pectoris and myocardial infarction: 15 p. 100, peripheral vascular disease: 7 p. 100, 37 p. 100 of patients had a stroke prior to entry. The ischemic event at entry occurred not more than one year prior to randomization and less than 3 months in 77 p. 100. It was much more often a completed stroke (84 p. 100) than a transient ischaemic attack (16 p. 100) and was referrable either to the carotid (46 p. 100) or the vertebrobasilar circulation (50 p. 100). On the whole patients are older and strokes more severe than in other similar studies. Randomization produced remarkably comparable treatment groups since almost no significant difference was observed between the 3 groups.

[Controlled cooperative trial of secondary prevention of cerebral ischemic accidents caused by atherosclerosis, using aspirin and dipyridamole]. / Essai coopératif contrôlé de prévention secondaire des accidents ischémiques cérébraux liés à l'athérosclérose par l'aspirine et le dipyridamole.

Six hundred and four patients with atherothrombotic cerebral ischemic events (transient: 16% or completed: 84%) referable either to the carotid or to the vertebral-basilar circulation were entered into a double blind randomized clinical trial (AICLA) to determine whether aspirin (A) (1 g/day) or aspirin (1 g) + dipyridamole (225 mg) (AD) would produce a significant reduction in the subsequent (3 years) occurrence of fatal and non fatal cerebral infarction. Randomization produced remarkably comparable treatment groups and this good comparability was maintained throughout the study. Adherence to the protocol and drug compliance were excellent. Side effects, particularly peptic ulcers and bleedings of various origin, were significantly (p less than 0.03) more frequent in the two treatment groups containing aspirin. At the end of the study (3 years), the number of fatal and non fatal cerebral infarction was 31 in the P group (placebo), 17 in the A group and 18 in the AD group. Taking into account the duration of follow up for each patient, these figures correspond to cumulate rates of 18% in the P group and 10.5% in the 2 others. Analysis with the Mantel Method showed: a difference at the 6% level between the 3 groups and between P and AD; a difference at the 5% level between P and A; no difference between A and AD; a difference at the 2% level between the P group and the two treated groups taken together (A + AD).(ABSTRACT TRUNCATED AT 250 WORDS)

[Ultrasonic study of the internal carotid artery]. / Exploration ultrasonore de l'artère carotide interne.

Investigation of the internal carotid arteries by ultrasound has revolutionized the prescription of complementary examinations in ischemic cerebral accidents. There are four techniques: 1) continuous Doppler, 2) CT scan with classical Doppler 3) CT scan with colour Doppler and 4) transcranial Doppler. The complementary of these investigations makes it possible to obtain hemodynamic and morphological information on the internal carotid artery from its cervical origin to its intracranial terminal. Reliable diagnosis of atherosclerotic carotid stenoses and occlusions has considerably reduced the need for angiography. Intracranial circulation can be studied by transcranial Doppler. This technique allows evaluation of the hemodynamic influence of extracranial carotid stenoses and occlusions, and diagnosis of hemodynamic stenoses in the intracranial internal carotid artery. Assessment of the thickness of the intima plus tunica media of the primary carotid artery by CT scan appears to be a sensitive marker of cerebral and coronary ischemic risk.

Use of monitoring software to improve the measurement of carotid wall thickness by B-mode imaging.

METHODOLOGY: High-resolution B-mode imaging is a reliable, easily performed and non-invasive means of studying atherosclerosis in superficial blood vessels. Recently it has been used for in vivo studies on the thickness of the common carotid artery wall. It is very sensitive, although the results of practical investigations are highly dependent on both the operator and the direction and angle of ultrasound beams directed towards the vessel. PROTOCOL: We have assessed inter- and intra-observer reproducibility of the measurement of common carotid artery wall thickness in 13 subjects, using two procedures. The first was a standard echographical investigation. In the second procedure, the principal parameters recorded from the first investigation were used to reposition the beam with the same incident angle. RESULTS: Intra-observer variability (correlation coefficient, r = 0.61 for procedure 1 and r = 0.77 for procedure 2) and inter-observer variation (r = 0.58 for procedure 1 and r = 0.71 for procedure 2) were reduced when the second investigation was assisted by reproducibility software. CONCLUSIONS: The proposed method is a reliable and reproducible way of assessing combined intimal and medial wall thickness in the common carotid artery. It may be possible to improve reproducibility using specific software to aid the operator. Since the intimal and medial thickness of the common carotid artery appears to be a sensitive marker of vascular risk, the proposed standardized method of measuring these parameter may allow early detection and assessment of changes.