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.

Mannheim carotid intima-media thickness consensus (2004-2006). An update on behalf of the Advisory Board of the 3rd and 4th Watching the Risk Symposium, 13th and 15th European Stroke Conferences, Mannheim, Germany, 2004, and Brussels, Belgium, 2006.

Intima-media thickness (IMT) is increasingly used as a surrogate end point of vascular outcomes in clinical trials aimed at determining the success of interventions that lower risk factors for atherosclerosis and associated diseases (stroke, myocardial infarction and peripheral artery diseases). The necessity to promote further criteria to distinguish early atherosclerotic plaque formation from thickening of IMT and to standardize IMT measurements is expressed through this updated consensus. Plaque 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. Standard use of IMT measurements is based on physics, technical and disease-related principles as well as agreements on how to perform, interpret and document study results. Harmonization of carotid image acquisition and analysis is needed for the comparison of the IMT results obtained from epidemiological and interventional studies around the world. The consensus concludes that there is no need to 'treat IMT values' nor to monitor IMT values in individual patients apart from exceptions named, which emphasize that inside randomized clinical trials should be performed. Although IMT has been suggested to represent an important risk marker, according to the current evidence it does not fulfill the characteristics of an accepted risk factor. Standardized methods recommended in this consensus statement will foster homogenous data collection and analysis. This will help to improve the power of randomized clinical trials incorporating IMT measurements and to facilitate the merging of large databases for meta-analyses.

In vivo middle cerebral artery plaque imaging by high-resolution MRI.

Middle cerebral artery (MCA) atherosclerosis is currently diagnosed by indirect angiographic methods. The authors used high-resolution MRI (HR-MRI) to study MCA stenosis in six patients. At the level of stenosis, an MCA plaque was clearly delineated and significantly measured vs nonatherosclerotic MCA segments, showing that HR-MRI is an accurate direct imaging method.

Cognitive impairment and carotid atherosclerosis in a general Italian midlife and old population.

The authors describe the design and the general, ultrasonographic, neuropsychological methodology of an observational epidemiological population survey, named REMEMBER (Registry Evaluation Memory in Buttrio e Remanzacco) conducted in the northeast of Italy in a randomized stratified sample of 1,026 subjects (554 F and 472 M) aged 55-98 years. The study was planned as cross-sectional and longitudinal survey of cognitive impairment, cardiovascular risk factors, carotid atherosclerosis in a midlife and older Italian population sample. The objectives of the first phase are to assess the prevalence of the different types of dementia, the cognitive impairment non-dementia, the cardiovascular risk factors, the carotid intima-media thickness and arterial distensibility, and of depression. The conclusions of this study will make it possible to organize preventive and interventional strategies for these epidemic conditions.

Detection and management of associated atherothrombotic locations in patients with a recent atherothrombotic ischemic stroke: results of the DETECT survey.

BACKGROUND: Cerebral infarction (CI), myocardial infarction, peripheral artery disease (PAD) and aortic atheroma are the main clinical manifestations of atherothrombosis. Long-term prevention after CI of atherothrombotic origin may require preventive measures at other sites, such as specific drug therapies, surgery, or angioplasty. Therefore the detection of other locations is potentially important. OBJECTIVES: The primary objective was to describe the other locations of atherothrombosis in patients hospitalized for a recent cerebral infarct of atherothrombotic origin. Secondary objectives were to describe their vascular risk factor profiles, and their management before and after the cerebral event. METHOD: This prospective, observational, multicenter survey was conducted in France between September 2003 and July 2004, mainly in neurological departments and stroke units. RESULTS: 753 patients were included (74% men; mean age 69.3 years). Previous coronary events had occurred in 119 (16%). Previous stroke or transient ischemic attacks had occurred in 233 (31%). PAD was already known in 109 (15%). A search for other atherothrombotic locations was positive in 216 patients (29%). The minimum prevalence for any associated atherothrombotic location (either present before or identified during hospitalization) was 47.5% for any location, 33.7% for coronary artery disease, 16.6% for aortic atheroma, and 22.7% for PAD. CONCLUSION: Fifty percent of the patients with recent atherothrombotic CI have other locations of atherothrombosis. For this reason, a systematic search for these other locations is recommended because of the possible therapeutic consequences. However, the question of the most appropriate period for this search after the cerebral event remains unsettled.

Design, baseline characteristics and carotid intima-media thickness reproducibility in the PARC study.

BACKGROUND: Intima-media thickness (IMT) is associated with an increased risk of cardiovascular and cerebral ischemic events, but its correlation with the absolute cardiovascular risk is not known in large populations. The Paroi Arterielle et Risque Cardiovasculaire (PARC) Study is an epidemiological study designed to correlate conventional assessment of cardiovascular risk with the mean IMT of the common carotid. METHODS: In the PARC study, 6,416 subjects were enrolled, including 80.7% subjects with cardiovascular risk factors and 19.3% without. A specific methodology was designed to harmonize the acquisition and processing of data at the 283 centers. Interreader agreement on image quality and IMT measurement of the common carotid artery (CCAIMT) was assessed from a random sample of 10% of the PARC study population. RESULTS: The intraclass correlation coefficient was 0.98 (95% CI 0.966-0.985), and the accuracy was high (standard deviation of the error measurement: 0.0185 mm). CONCLUSIONS: The reproducibility of the measurements assessed by means of the intraclass correlation coefficient and the accuracy of the CCAIMT measurement obtained in the PARC Study demonstrate the feasibility of large multicenter studies of IMT measurement.

Intracranial arterial dolichoectasia is associated with enlarged descending thoracic aorta.

BACKGROUND: Intracranial arterial dolichoectasia (IADE) is defined as an increase in length and diameter of the intracranial arteries and is present in 12% of stroke patients. The pathophysiology is unknown; some data suggest that IADE is not merely a complication of atherosclerosis, but a distinct arteriopathy characterized by loss of elastic tissue in the media. OBJECTIVE: To investigate the relationship between IADE and transesophageal echocardiography (TEE) variables such as ascending and descending thoracic aorta diameters. METHODS: The sample included 154 patients with brain infarction (BI) and with measurement of the descending thoracic aorta on TEE. IADE was diagnosed by consensus between two neurologists. Information on demographic characteristics and risk factors was collected using a structured questionnaire, and a carotid ultrasound scan was performed. RESULTS: IADE was identified in 23 of the 154 stroke patients (15%). The mean diameter (+/-SD) of the descending thoracic aorta was significantly higher in the IADE(+) than in the 131 IADE(-) stroke patients (mean +/- SD 26.6 +/- 3.6 vs 24.8 +/- 2.7 mm). The proportion of IADE increased regularly with the quartiles of descending thoracic aorta diameter: 5%, 13%, 18%, and 24% (test of linear trend, p = 0.02). The adjusted OR (95% CI) of IADE associated with a 1 mm increase in descending thoracic aorta diameter was 1.22 (95% CI, 1.02 to 1.45). CONCLUSION: Patients with intracranial arterial dolichoectasia (IADE) have larger descending thoracic aorta diameters than non-IADE patients, suggesting that the underlying process causing IADE also affects the descending thoracic aorta.

Mannheim intima-media thickness consensus.

Intima-media thickness (IMT) is increasingly used in clinical trials as a surrogate end point for determining the success of interventions that lower risk factors for atherosclerosis. The necessity for unified criteria to distinguish early atherosclerotic plaque formation from thickening of IMT and to standardize IMT measurements is addressed in this consensus statement. Plaque 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 of > or =1.5 mm as measured from the media-adventitia interface to the intima-lumen interface. Standard use of IMT measurements is recommended in all epidemiological and interventional trials dealing with vascular diseases to improve characterization of the population investigated. The consensus concludes that there is no need to 'treat IMT values' nor to monitor IMT values in individual patients apart from few exceptions. Although IMT has been suggested to represent an important risk marker, it does not fulfill the characteristics of an accepted risk factor. Standardized methods recommended in this consensus statement will foster homogenous data collection and analysis. This will help to improve the power of studies incorporating IMT measurements and to facilitate the merging of large databases for meta-analyses.

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.

Low cerebral blood flow velocity and risk of white matter hyperintensities.

Cerebral blood flow velocity (CBF-V) measured by transcranial doppler was assessed in 628 elderly individuals who had cerebral magnetic resonance imaging performed as part of a population-based study on vascular aging. Cerebral white matter hyperintensities (WMHs) were associated with low CBF-V, such as the adjusted odds ratios of severe WMHs from highest (referent) to lowest quartile of mean CBF-V were 1.0, 1.7, 3.7, and 4.3 (p = 0.001). Further, CBF-V was found to be a stronger risk factor for WMHs than high blood pressure. These findings suggest that the assessment of CBF-V might be a powerful tool in future studies on WMHs.

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.

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.

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.

Common carotid intima-media thickness predicts occurrence of carotid atherosclerotic plaques: longitudinal results from the Aging Vascular Study (EVA) study.

The role of the increase in the common carotid artery (CCA) intima-media wall thickness (IMT) in the atherosclerotic process is questionable. This longitudinal study examined the predictive value of CCA-IMT measured at baseline examination (at sites free of plaques) on the occurrence of atherosclerotic plaques in the extracranial carotid arteries during 4 years of follow-up study in a sample of 1010 subjects aged 59 to 71 years. Ultrasound examinations were performed at baseline and 2 years and 4 years later. The occurrence of carotid plaques during follow-up was defined as the appearance of >/=1 plaque in previously normal carotid segments and/or the appearance of new plaques in the carotid segments that previously had plaques. Carotid plaque occurrence was observed in 185 subjects (18.3%). Age- and sex- adjusted odds ratios of carotid plaque occurrence were 2.66 (95% CI 1.58 to 4.46, P<0.001) in subjects having intermediate baseline CCA-IMT values (quartiles 2 and 3) and 3.67 (CI 2.09 to 6.44, P<0.001) in those having the highest baseline CCA-IMT values (quartile 4) compared with those having the lowest baseline CCA-IMT values (quartile 1). Multivariate adjustment for major cardiovascular risk factors did not alter the results. These findings were observed for men and women as well as for subjects with and without carotid plaques at baseline. This 4-year longitudinal study shows that CCA-IMT predicts carotid plaque occurrence in a large sample of relatively old subjects. It extends the findings obtained from cross-sectional studies and suggests that increased intima-media thickness might occur in an earlier phase of the atherosclerotic process.

Cross-sectional and 4-year longitudinal associations between brachial pulse pressure and common carotid intima-media thickness in a general population. The EVA study.

BACKGROUND AND PURPOSE: The cross-sectional and 4-year longitudinal associations between brachial pulse pressure (PP) and ultrasound measurements of common carotid intima-media thickness (CCA-IMT) were assessed. METHODS: A population of 957 volunteers aged 59 to 71 years was recruited from the electoral rolls of the city of Nantes (western France) and reexamined 4 years later. Longitudinal changes in PP and CCA-IMT were computed as the difference between 4-year follow-up and baseline values. RESULTS: Baseline CCA-IMT and PP were positively associated in both age- and sex-adjusted analysis (partial correlation coefficient=0.20, P<0.001) and in multivariate analysis adjusted for traditional cardiovascular risk factors and mean blood pressure (partial correlation coefficient=0.18, P<0.001). In longitudinal analysis, baseline PP was associated with the change in 4-year CCA-IMT (partial correlation coefficient=0.11, P<0.001), and baseline CCA-IMT was a predictor of the 4-year change in PP (partial correlation coefficient=0.10, 0.001

Differential association of common carotid intima-media thickness and carotid atherosclerotic plaques with parental history of premature death from coronary heart disease : the EVA study.

Familial aggregation of coronary heart disease (CHD) has been reported in several studies. The specific underlying mechanisms and the relative contribution of atherosclerosis to the subsequent CHD events in subjects with family history are not well established. This study examined the association of parental history of premature death from CHD with ultrasound carotid measurements of atherosclerosis in a population of 1040 subjects aged 59 to 71 years. Ultrasound examination included measurements of intima-media thickness at the common carotid arteries (at sites free of plaques) and assessment of atherosclerotic plaques in the extracranial carotid arteries. Subjects who reported that 1 or both parents had sudden death or died of myocardial infarction before the age of 65 years were considered positive for parental history of premature death from CHD (n=53, 5.1%). The prevalence of atheromatous plaques was higher in subjects with history of premature death from CHD compared with those without history (41.5% versus 20.5%, P<0.001). Age- and sex-adjusted odds ratio of atheromatous plaques associated with parental history of premature death from CHD was 2.85 (95% confidence interval, 1.60 to 5.08; P<0.001). Multivariate adjustment for major known cardiovascular risk factors did not markedly alter the results (odds ratio, 2.70; P<0.002). In contrast, common carotid intima-media thickness was not associated with parental history of premature death from CHD (0.66+/-0.11 versus 0.66+/-0.12 mm, P=0.76). These findings were observed in both men and women. In conclusion, parental history of premature death from CHD is strongly associated with carotid plaques. Familial transmission of CHD risk does not seem to be specifically mediated by arterial wall thickening measured at sites free of plaques.