Geographic differences in outcomes in outpatients with established atherothrombotic disease: results from the REACH Registry.

AIMS: There are major differences in the prevalence and management of patients with atherothrombotic disease including coronary artery disease (CAD), cerebrovascular disease (CVD) and peripheral artery disease (PAD) across different geographical regions. There is, however, little data allowing comparisons of management and outcomes across broad geographic regions. We aimed to describe geographical differences in baseline characteristics, management and outcomes in stable outpatients with established atherothrombotic disease. METHODS AND RESULTS: From the REACH Registry of atherothrombosis, patients with documented CAD, PAD or CVD and with 4-year follow-up were included. Baseline characteristics, treatments and 4-year outcomes were recorded. Event rates were compared between geographical regions and were adjusted for risk scores predicting ischemic and bleeding events. The analyses of baseline characteristics and medications according to geographical region showed marked differences. For the composite primary outcome (cardiovascular death, non-fatal myocardial infarction (MI) and non-fatal stroke), rates ranged from 12.1% in Japan to 18.2% in Eastern Europe. After adjustment, substantial variations remained: taking North America as a reference, patients from Western Europe and Japan had a lower risk of primary outcome event (hazard ratio (HR) 0.93; p = 0.045, and HR = 0.67; p < 0.001 respectively) whereas patients from Eastern Europe had a higher risk (HR = 1.24; p < 0.001). There were no obvious differences between patients from North America and those from Latin America, the Middle East and Asia. CONCLUSION: There are important variations in the outcomes of patients with atherothrombotic across geographic regions. These observations have important implications for public health and clinical research.

The ASCOD phenotyping of ischemic stroke (Updated ASCO Phenotyping).

ASCO phenotyping (A: atherosclerosis; S: small-vessel disease; C: cardiac pathology; O: other causes) assigns a degree of likelihood of causal relationship to every potential disease (1 for potentially causal, 2 for causality is uncertain, 3 for unlikely causal but the disease is present, 0 for absence of disease, and 9 for insufficient workup to rule out the disease) commonly encountered in ischemic stroke describing all underlying diseases in every patient. In this new evolution of ASCO called ASCOD, we have added a 'D' for dissection, recognizing that dissection is a very frequent disease in young stroke patients. We have also simplified the system by leaving out the 'levels of diagnostic evidence', which has been integrated into grades 9 and 0. Moreover, we have also changed the cutoff for significant carotid or intracranial stenosis from 70% to more commonly used 50% luminal stenosis, and added a cardiogenic stroke pattern using neuroimaging. ASCOD captures and weights the overlap between all underlying diseases present in ischemic stroke patients.

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.

Early stroke risk and ABCD2 score performance in tissue- vs time-defined TIA: a multicenter study.

OBJECTIVES: Stroke risk immediately after TIA defined by time-based criteria is high, and prognostic scores (ABCD2 and ABCD3-I) have been developed to assist management. The American Stroke Association has proposed changing the criteria for the distinction between TIA and stroke from time-based to tissue-based. Research using these definitions is lacking. In a multicenter observational cohort study, we have investigated prognosis and performance of the ABCD2 score in TIA, subcategorized as tissue-positive or tissue-negative on diffusion-weighted imaging (DWI) or CT imaging according to the newly proposed criteria. METHODS: Twelve centers provided data on ABCD2 scores, DWI or CT brain imaging, and follow-up in cohorts of patients with TIA diagnosed by time-based criteria. Stroke rates at 7 and 90 days were studied in relation to tissue-positive or tissue-negative subcategorization, according to the presence or absence of brain infarction. The predictive power of the ABCD2 score was determined using area under receiver operator characteristic curve (AUC) analyses. RESULTS: A total of 4,574 patients were included. Among DWI patients (n = 3,206), recurrent stroke rates at 7 days were 7.1%(95% confidence interval 5.5-9.1) after tissue-positive and 0.4% (0.2-0.7) after tissue-negative events (p diff < 0.0001). Corresponding rates in CT-imaged patients were 12.8% (9.3-17.4) and 3.0% (2.0-4.2), respectively (p diff < 0.0001). The ABCD2 score had predictive value in tissue-positive and tissue-negative events (AUC = 0.68 [95% confidence interval 0.63-0.73] and 0.73 [0.67-0.80], respectively; p sig < 0.0001 for both results, p diff = 0.17). Tissue-positive events with low ABCD2 scores and tissue-negative events with high ABCD2 scores had similar stroke risks, especially after a 90-day follow-up. CONCLUSIONS: Our findings support the concept of a tissue-based definition of TIA and stroke, at least on prognostic grounds.

Atherothrombosis and the role of antiplatelet therapy.

Atherothrombosis remains a major global public health problem. Chronic atherosclerotic disease is often clinically silent and coexists across vascular beds, but when complicated by thrombosis can result in acute coronary syndrome, stroke, transient ischaemic attack and critical limb ischaemia. Platelets play a role in the development of chronic atherosclerotic disease and are a key mediator of clinical events in atherothrombosis. Numerous trials have examined the role of antiplatelet agents in primary and secondary prevention and several new antiplatelet drugs are under development. In secondary prevention, there is evidence of clear benefit of single and in some cases dual antiplatelet therapy in the prevention of recurrent cerebro-vascular complications. Dual antiplatelet therapy has emerged as the standard of care in acute coronary syndromes, with aspirin typically being used in combination with clopidogrel or one of the newer more potent antiplatelet agents. Conversely, in chronic stable coronary disease, no benefit has yet been convincingly demonstrated from dual antiplatelet therapy. In cerebro-vascular disease, aspirin monotherapy remains the cornerstone of prevention of recurrent events, with clopidogrel or the combination of aspirin and dipyridamole being only modestly more efficacious. In primary prevention, the evidence for the routine use of aspirin or any other antiplatelet agent is mixed and suggests this should only be considered on an individual basis in high-risk groups where the thrombotic risk outweighs the risk of major bleeding complications.

Prevalence of subdiaphragmatic visceral infarction in cardioembolic stroke.

BACKGROUND: A substantial proportion of ischemic strokes have an embolic mechanism, but the source of embolism is not detected. Coexistence of subdiaphragmatic visceral infarction (SDVI; e.g., renal, splenic, hepatic, bowel infarction) may be a suggestion of a common source of embolism. One large autopsy study found SDVI in 21.5% of patients with fatal stroke. METHOD: We performed diffusion-weighted magnetic resonance abdominal imaging and subsequently performed it in consecutive patients with stroke or TIA and a history of nonvalvular atrial fibrillation. RESULTS: Among 27 patients, 6 had SDVI (3 recent renal, 1 recent splenic, and 3 old splenic infarction). The median time between onset of ischemic stroke and abdominal MRI was 8 days (interquartile range 3-15 days). No predictive factor of SDVI was found in this study population with respect to demographic or ultrasound characteristics. CONCLUSIONS: One in 5 patients with nonfatal cardioembolic stroke or TIA may be associated with subdiaphragmatic visceral infarction (SDVI). Further study should evaluate the frequency of SDVI in patients with stroke of unknown cause.

Glucose level and brain infarction: a prospective case-control study and prospective study.

BACKGROUND: Hyperglycaemia in the acute phase of stroke has been established as a predictor of higher mortality. But recent data regarding active treatment of hyperglycaemia showed no clinical benefit suggesting that hyperglycaemia may not have a detrimental effect in brain infarction. Additional data are needed to resolve this uncertainty and identify patients at higher risk if any. METHODS: A total of 477 adult Caucasian patients with brain infarction and 395 age- and sex-matched controls admitted at the same centres for nonneurological causes were recruited consecutively from 12 neurological centres in France. Electrocardiographic, carotid ultrasonography, and transcranial Doppler studies were performed. Blood was drawn in the morning from fasting subjects for glucose measurement. Functional outcome was measured on admission, at 10 days and at 6 months after the onset of stroke using the modified Rankin scale. RESULTS: Among 477 brain infarction patients and 395 hospitalised controls the adjusted mean (+/-SEM) glucose level was higher in cases (6.4+/-1.0 mmol/l) than in controls (6.0+/-1.01 mmol/l, P=0.006), with a significant heterogeneity across sexes. The fully adjusted odds ratio of brain infarction per 1-standard deviation increase in log-glucose level was 1.02 (95% confidence interval, 0.77-1.37) in men and 2.21 (95% confidence interval, 1.44-3.40) in women. Among the 477 brain infarction cases elevated admission glucose levels were associated with poor outcomes and higher poststroke mortality after adjustment for conventional vascular risk factors and infarct volume. These relationships were not modified by sex. CONCLUSIONS: Elevated admission glucose levels were associated with brain infarction in women only and with a higher 5-year mortality. Further investigation focusing on the impact of glucose level in different target population is needed to optimise glycaemic management in acute brain infarction patients.

The Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic attack (PERFORM) study: baseline characteristics of the population.

BACKGROUND: The Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic attack (PERFORM) study is an international double-blind, randomized controlled trial designed to investigate the superiority of the specific TP receptor antagonist terutroban (30 mg/day) over aspirin (100 mg/day), in reducing cerebrovascular and cardiovascular events in patients with a recent history of ischemic stroke or transient ischemic attack. Here we describe the baseline characteristics of the population. METHODS AND RESULTS: Parameters recorded at baseline included vital signs, risk factors, medical history, and concomitant treatments, as well as stroke subtype, stroke-associated disability on the modified Rankin scale, and scores on scales for cognitive function and dependency. Eight hundred and two centers in 46 countries recruited a total of 19,119 patients between February 2006 and April 2008. The population is evenly distributed and is not dominated by any one country or region. The mean +/- SD age was 67.2 +/- 7.9 years, 63% were male, and 83% Caucasian; 83% had hypertension, and about half the population smoked or had quit smoking. Ninety percent of the qualifying events were ischemic stroke, 67% of which were classified as atherothrombotic or likely atherothrombotic (pure or coexisting with another cause). Modified Rankin scale scores showed slight or no disability in 83% of the population, while the scores on the Mini-Mental State Examination, Isaacs' Set Test, Zazzo's Cancellation Test, and the instrumental activities of daily living scale showed a good level of cognitive function and autonomy. CONCLUSIONS: The PERFORM study population is homogeneous in terms of demographic and disease characteristics. With 19,119 patients, the PERFORM study is powered to test the superiority of terutroban over aspirin in the secondary prevention of cerebrovascular and cardiovascular events in patients with a recent history of ischemic stroke or transient ischemic attack.

Rationale and design of a randomized, double-blind, parallel-group study of terutroban 30 mg/day versus aspirin 100 mg/day in stroke patients: the prevention of cerebrovascular and cardiovascular events of ischemic origin with terutroban in patients with a history of ischemic stroke or transient ischemic attack (PERFORM) study.

BACKGROUND: Ischemic stroke is the leading cause of mortality worldwide and a major contributor to neurological disability and dementia. Terutroban is a specific TP receptor antagonist with antithrombotic, antivasoconstrictive, and antiatherosclerotic properties, which may be of interest for the secondary prevention of ischemic stroke. This article describes the rationale and design of the Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic Attack (PERFORM) Study, which aims to demonstrate the superiority of the efficacy of terutroban versus aspirin in secondary prevention of cerebrovascular and cardiovascular events. METHODS AND RESULTS: The PERFORM Study is a multicenter, randomized, double-blind, parallel-group study being carried out in 802 centers in 46 countries. The study population includes patients aged > or =55 years, having suffered an ischemic stroke (< or =3 months) or a transient ischemic attack (< or =8 days). Participants are randomly allocated to terutroban (30 mg/day) or aspirin (100 mg/day). The primary efficacy endpoint is a composite of ischemic stroke (fatal or nonfatal), myocardial infarction (fatal or nonfatal), or other vascular death (excluding hemorrhagic death of any origin). Safety is being evaluated by assessing hemorrhagic events. Follow-up is expected to last for 2-4 years. Assuming a relative risk reduction of 13%, the expected number of primary events is 2,340. To obtain statistical power of 90%, this requires inclusion of at least 18,000 patients in this event-driven trial. The first patient was randomized in February 2006. CONCLUSIONS: The PERFORM Study will explore the benefits and safety of terutroban in secondary cardiovascular prevention after a cerebral ischemic event.

Classification of stroke subtypes.

This article reviews published stroke subtype classification systems and offers rules and a basis for a new way to subtype stroke patients. Stroke subtyping can have different purposes, e.g. describing patients' characteristics in a clinical trial, grouping patients in an epidemiological study, careful phenotyping of patients in a genetic study, and classifying patients for therapeutic decision-making in daily practice. The classification should distinguish between ischemic and hemorrhagic stroke, subarachnoid hemorrhage, cerebral venous thrombosis, and spinal cord stroke. Regarding the 4 main categories of etiologies of ischemic stroke (i.e. atherothrombotic, small vessel disease, cardioembolic, and other causes), the classification should reflect the most likely etiology without neglecting the vascular conditions that are also found (e.g. evidence of small vessel disease in the presence of severe large vessel obstructions). Phenotypes of large cohorts can also be characterized by surrogate markers or intermediate phenotypes (e.g. presence of internal carotid artery plaque, intima-media thickness of the common carotid artery, leukoaraiosis, microbleeds, or multiple lacunae). Parallel classifications (i.e. surrogate markers) may serve as within-study abnormalities to support research findings.

New approach to stroke subtyping: the A-S-C-O (phenotypic) classification of stroke.

We now propose a new approach to stroke subtyping. The concept is to introduce a complete 'stroke phenotyping' classification (i.e. stroke etiology and the presence of all underlying diseases, divided by grade of severity) as distinguished from past classifications that subtype strokes by characterizing only the most likely cause(s) of stroke. In this phenotype-based classification, every patient is characterized by A-S-C-O: A for atherosclerosis, S for small vessel disease, C for cardiac source, O for other cause. Each of the 4 phenotypes is graded 1, 2, or 3. One for 'definitely a potential cause of the index stroke', 2 for 'causality uncertain', 3 for 'unlikely a direct cause of the index stroke (but disease is present)'. When the disease is completely absent, the grade is 0; when grading is not possible due to insufficient work-up, the grade is 9. For example, a patient with a 70% ipsilateral symptomatic stenosis, leukoaraiosis, atrial fibrillation, and platelet count of 700,000/mm(3) would be classified as A1-S3-C1-O3. The same patient with a 70% ipsilateral stenosis, no brain imaging, normal ECG, and normal cardiac imaging would be identified as A1-S9-C0-O3. By introducing the 'level of diagnostic evidence', this classification recognizes the completeness, the quality, and the timing of the evaluation to grade the underlying diseases. Diagnostic evidence is graded in levels A, B, or C: A for direct demonstration by gold-standard diagnostic tests or criteria, B for indirect evidence or less sensitive or specific tests or criteria, and C for weak evidence in the absence of specific tests or criteria. With this new way of classifying patients, no information is neglected when the diagnosis is made, treatment can be adapted to the observed phenotypes and the most likely etiology (e.g. grade 1 in 1 of the 4 A-S-C-O phenotypes), and analyses in clinical research can be based on 1 of the 4 phenotypes (e.g. for genetic analysis purpose), while clinical trials can focus on 1 or several of these 4 phenotypes (e.g. focus on patients A1-A2-A3).

Prevalence of nephroangiosclerosis in patients with fatal stroke.

BACKGROUND: Glomerular filtration rate and decline in renal function can be improved by global cardiovascular prevention. However, the prevalence of nephroangiosclerosis in patients with stroke is unknown. METHODS: Using an autopsy data bank, we studied the prevalence of nephroangiosclerosis in 820 consecutive autopsies of neurologic patients. RESULTS: Among the 820 autopsies, 354 had pathologic evidence of stroke and 466 had other neurologic diseases. Nephroangiosclerosis was found in 39.8% (95% confidence interval [CI], 34.7-44.9) of patients with stroke vs 9.0% (95% CI, 6.4-11.6) in patients with other neurologic diseases. The odds ratio (OR) for nephroangiosclerosis, adjusted for age and sex, was 4.37 (95% CI, 2.92-6.52), and was 2.94 (95% CI, 1.83-4.74) after further adjustment for cardiovascular risk factors. Among the 354 stroke patients, the prevalence of nephroangiosclerosis was similar in patients with brain infarction and in those with brain hemorrhage, in patients with or without parenchymal abnormalities related to small-vessel disease, and across ischemic stroke subtypes except for those with coexisting causes. After multivariable analysis, nephroangiosclerosis was independently associated with age and history of hypertension in patients with stroke, and with age in those with other neurologic diseases. CONCLUSIONS: Nephroangiosclerosis is common in patients with fatal stroke. The association is independent of age, sex, and other cardiovascular risk factors. Impaired renal function should be monitored and prevented in stroke patients with high blood pressure.

Effect of atorvastatin in elderly patients with a recent stroke or transient ischemic attack.

BACKGROUND: It is unclear whether patients age 65 years and over with a recent stroke or TIA benefit from statin treatment to a similar degree as younger patients. METHODS: The 4,731 patient cohort in the SPARCL study was divided into an elderly group (65 and over) and a younger group. The primary endpoint (fatal or nonfatal stroke) and secondary endpoints were analyzed, with calculation of the hazard ratio (HR) and p values from a Cox regression model. RESULTS: There were 2,249 patients in the elderly group and 2,482 in the younger group. The baseline LDL (133 mg/dL) and total cholesterol were comparable in the two groups. The elderly and younger groups had a 61.4 mg/dL and 58.7 mg/dL decrease in mean LDL during the trial. The primary endpoint was reduced by 26% in younger patients (HR 0.74, 0.57-0.96, p = 0.02) and by 10% in elderly subjects (HR 0.90, 0.73-1.11, p = 0.33). A test of heterogeneity for a treatment-age interaction was not significant (p = 0.52). The risk of stroke or TIA (HR 0.79, p = 0.01), major coronary events (HR 0.68, p = 0.035), any coronary heart disease event (HR 0.61, p = 0.0006), and revascularization procedures (HR 0.55, p = 0.0005) was reduced in the elderly group. CONCLUSIONS: There was no heterogeneity in the stroke reduction seen with atorvastatin in the elderly and younger groups. Cardiac events and revascularization procedures were also lower in both the elderly and younger subgroups treated with atorvastatin. These results support the use of atorvastatin in elderly patients with recent stroke or TIA.

[Update on vascular dementias]. / Mise au point sur les démences vasculaires.

The concept of vascular dementia greatly evolved since Hachinski's description of multi-infarct dementia. Vascular dementias are reviewed with emphasis on current diagnostic criteria, elusive natural history, neuroradiological aspects, difficult epidemiological features and intriguing links with Alzheimer's disease. The recent proposed shift from vascular dementias to a broader definition of "vascular cognitive disorders", including non demented subjects with "vascular cognitive impairment", is described, followed by a brief review of current treatments.

Hemorrhagic stroke in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels study.

BACKGROUND: In the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study, atorvastatin 80 mg/day reduced the risk of stroke in patients with recent stroke or TIA. Post hoc analysis found this overall benefit included an increase in the numbers of treated patients having hemorrhagic stroke (n = 55 for active treatment vs n = 33 for placebo). METHODS: We explored the relationships between hemorrhage risk and treatment, baseline patient characteristics, most recent blood pressure, and most recent low-density lipoprotein (LDL) cholesterol levels prior to the hemorrhage. RESULTS: Of 4,731 patients, 67% had ischemic strokes, 31% TIAs, and 2% hemorrhagic strokes as entry events. In addition to atorvastatin treatment (HR 1.68, 95% CI 1.09 to 2.59, p = 0.02), Cox multivariable regression including baseline variables significant in univariable analyses showed that hemorrhagic stroke risk was higher in those having a hemorrhagic stroke as the entry event (HR 5.65, 95% CI 2.82 to 11.30, p < 0.001), in men (HR 1.79, 95% CI 1.13 to 2.84, p = 0.01), and with age (10 y increments, HR 1.42, 95% CI 1.16 to 1.74, p = 0.001). There were no statistical interactions between these factors and treatment. Multivariable analyses also found that having Stage 2 (JNC-7) hypertension at the last study visit before a hemorrhagic stroke increased risk (HR 6.19, 95% CI 1.47 to 26.11, p = 0.01), but there was no effect of most recent LDL-cholesterol level in those treated with atorvastatin. CONCLUSIONS: Hemorrhagic stroke was more frequent in those treated with atorvastatin, in those with a hemorrhagic stroke as an entry event, in men, and increased with age. Those with Stage 2 hypertension at the last visit prior to the hemorrhagic stroke were also at increased risk. Treatment did not disproportionately affect the hemorrhagic stroke risk associated with these other factors. There were no relationships between hemorrhage risk and baseline low-density lipoprotein (LDL) cholesterol level or recent LDL cholesterol level in treated patients.

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.