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Common carotid artery (CCA) intima-media thickness (IMT) is associated with coronary heart disease and can be measured on ultrasound images either by hand or with an automated edge detector. The association of CCA IMT with incident peripheral artery disease (PAD) is poorly studied. We studied 5467 participants of the Multi-Ethnic Study of Atherosclerosis composed of non-Hispanic white, Chinese, Hispanic, and African American participants with a mean age of 61.9 years (47.8% men). Framingham Risk Factors, manual-traced IMT (mt-IMT), and edge-detected IMT (ed-IMT) were entered into multivariable Cox proportional hazards models with incident PAD as the outcome. There were 87 events during a median follow-up of 12.2 years. In fully adjusted models and expressing the hazard ratios (HR) as an increment in SD values, both mt-IMT and ed-IMT were significantly associated with incident PAD: HR 1.36 (95% CI: 1.15, 1.61) and 1.29 (95% CI: 1.04, 1.60), respectively. We conclude that ed- and mt-CCA IMT measurements are associated with incident PAD. ClinicalTrials.gov Identifier: NCT00063440 .

Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.

Background: Common carotid artery and internal carotid artery intima-media thicknesses (IMT) are associated with coronary heart disease (CHD) and increase with age. Using age, sex, and race/ethnicity IMT percentiles may improve CHD prediction when added to Framingham risk factors and coronary artery calcium score. We study these possibilities in the Multi-Ethnic Study of Atherosclerosis (MESA), a multi-ethnic cohort of whites, Chinese, blacks, and Hispanics., Methods and Results: IMT data were acquired in the age range 45 to 84 years. Common carotid artery and internal carotid artery IMT, sex, and race/ethnic specific normative values were calculated for each MESA participant and combined as an IMT score. Multivariable Cox-proportional hazards models and logistic regression models were generated with CHD as outcome adding the IMT score to (1) a base model with Framingham risk factors, sex, race/ethnicity and (2) the base model with coronary artery calcium added. Harrell's C-statistics and area under the curve were estimated. Median follow-up was 10.2 years (interquartile range: 9.7, 10.7 years) with 429 first-time CHD events. Mean age was 62.1 years and 52.6% of participants were women. IMT score increased the base area under the curve from 0.7210 to 0.7396 (P=0.0008) and with positive coronary artery calcium score added to the model, from 0.7627 to 0.7714 (P=0.02)., Conclusions: A carotid IMT score based on normative data incrementally adds to Framingham risk factors and a positive calcium score in predicting first-time CHD in an ethnically diverse cohort., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Carotid artery intima-media thickness (IMT) is a noninvasive measurement of the artery wall thickness, inclusive of atherosclerotic plaque, obtained using ultrasound imaging. In the MESA (Multi-Ethnic Study of Atherosclerosis) study, IMT measurements are used as a surrogate for subclinical cardiovascular disease and as a variable predictive of cardiovascular events. IMT measurements of the common carotid artery are available in more than 99% of the MESA population and are predictive of cardiovascular events. More importantly, IMT and plaque thickness measurements made in the internal carotid artery and carotid bulb are also available in more than 98% of the population and are also strongly predictive of cardiovascular events. This article reviews the techniques used to obtain the MESA IMT values, compares them to those made in other epidemiological studies, and summarizes how they have been used in the MESA study as both surrogates for and predictors of cardiovascular disease., (Copyright © 2016. Published by Elsevier B.V.)

Background: Clinical manifestations and outcomes of atherosclerotic disease differ between ethnic groups. In addition, the prevalence of risk factors is substantially different. Primary prevention programs are based on data derived from almost exclusively White people. We investigated how race/ethnic differences modify the associations of established risk factors with atherosclerosis and cardiovascular events., Methods: We used data from an ongoing individual participant meta-analysis involving 17 population-based cohorts worldwide. We selected 60,211 participants without cardiovascular disease at baseline with available data on ethnicity (White, Black, Asian or Hispanic). We generated a multivariable linear regression model containing risk factors and ethnicity predicting mean common carotid intima-media thickness (CIMT) and a multivariable Cox regression model predicting myocardial infarction or stroke. For each risk factor we assessed how the association with the preclinical and clinical measures of cardiovascular atherosclerotic disease was affected by ethnicity., Results: Ethnicity appeared to significantly modify the associations between risk factors and CIMT and cardiovascular events. The association between age and CIMT was weaker in Blacks and Hispanics. Systolic blood pressure associated more strongly with CIMT in Asians. HDL cholesterol and smoking associated less with CIMT in Blacks. Furthermore, the association of age and total cholesterol levels with the occurrence of cardiovascular events differed between Blacks and Whites., Conclusion: The magnitude of associations between risk factors and the presence of atherosclerotic disease differs between race/ethnic groups. These subtle, yet significant differences provide insight in the etiology of cardiovascular disease among race/ethnic groups. These insights aid the race/ethnic-specific implementation of primary prevention.

Background: Common carotid artery intima-media thickness (IMT) can be measured either by hand or with an automated edge detector. We performed a direct comparison of these 2 approaches and studied their respective associations with coronary heart disease outcomes., Methods and Results: We studied 5468 participants of the Multi-Ethnic Study of Atherosclerosis, composed of white, Chinese, Hispanic, and black participants with an average age of 61.9 years (47.8% men) and who were free of coronary heart disease at baseline. Manual-traced and edge-detected IMT measurements were made in the same location on ultrasound images of the right common carotid artery far wall in an area free of plaque. Manual-traced and edge-detected common carotid artery IMT measurements were added separately to multivariable Cox proportional hazards models with time to incident coronary heart disease as the outcome and adjusted for traditional coronary heart disease Framingham risk factors, lipid-lowering therapy, blood pressure-lowering therapy, and race or ethnicity. Additional models were generated after adding clinic site and reader. There were 349 events during a median follow-up of 10.2 years. In adjusted models, the hazard ratio was not significant (1.31; 95% CI 0.84 to 2.06) for each millimeter increase in manual-traced IMT but was significant for edge-detected IMT (hazard ratio 1.63; 95% CI 1.12 to 2.37). Edge-detected IMT remained statistically associated with outcomes after additional adjustment for clinic site and reader performing the IMT measurement (hazard ratio 1.59; 95% CI 1.07 to 2.35)., Conclusions: Edge-detected common carotid artery far wall IMT has similar if not stronger associations with coronary heart disease outcomes when compared with manual-traced IMT., Clinical Trial Registration: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00063440., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Objective: To estimate atherosclerosis progression and identify influencing factors in rheumatoid arthritis (RA)., Methods: We used carotid ultrasound to measure intima-media thickness (IMT) in RA patients, and ascertained cardiovascular (CV) risk factors, inflammation markers and medications. A second ultrasound was performed approximately 3 years later. We calculated the progression rate by subtracting the baseline from the follow-up IMT, divided by the time between the two scans. We used logistic regression to identify baseline factors predictive of rapid progression. We tested for interactions of erythrocyte sedimentation rate (ESR) with CV risk factors and medication use., Results: Results were available for 487 RA patients. The mean (SD) common carotid IMT at baseline was 0.571 mm (0.151). After a mean of 2.8 years, the IMT increased by 0.050 mm (0.055), p≤0.001, a progression rate of 0.018 mm/year (95% CI 0.016 to 0.020). Baseline factors associated with rapid progression included the number of CV risk factors (OR 1.27 per risk factor, 95% CI 1.01 to 1.61), and the ESR (OR 1.12 per 10 mm/h, 95% CI 1.02 to 1.23). The ESR×CV risk factor and ESR×medication product terms were significant, suggesting these variables modify the association between the ESR and IMT progression., Conclusions: Systemic inflammation and CV risk factors were associated with rapid IMT progression. CV risk factors may modify the role of systemic inflammation in determining IMT progression over time. Methotrexate and antitumour necrosis factor agents may influence IMT progression by reducing the effect of the systemic inflammation on the IMT., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Although atherosclerosis starts in early life, evidence on risk factors and atherosclerosis in individuals aged <45 years is scarce. Therefore, we studied the relationship between risk factors, common carotid intima-media thickness (CIMT), and first-time cardiovascular events in adults aged <45 years. Our study population consisted of 3067 adults aged <45 years free from symptomatic cardiovascular disease at baseline, derived from 6 cohorts that are part of the USE-IMT initiative, an individual participant data meta-analysis of general-population-based cohort studies evaluating CIMT measurements. Information on risk factors, CIMT measurements, and follow-up of the combined end point (first-time myocardial infarction or stroke) was obtained. We assessed the relationship between risk factors and CIMT and the relationship between CIMT and first-time myocardial infarction or stroke using a multivariable linear mixed-effects model and a Cox proportional-hazards model, respectively. During a follow-up of 16.3 years, 55 first-time myocardial infarctions or strokes occurred. Median CIMT was 0.63 mm. Of the risk factors under study, age, sex, diastolic blood pressure, body mass index, total cholesterol, and high-density lipoprotein cholesterol related to CIMT. Furthermore, CIMT related to first-time myocardial infarction or stroke with a hazard ratio of 1.40 per SD increase in CIMT, independent of risk factors (95% confidence interval, 1.11-1.76). CIMT may be a valuable marker for cardiovascular risk in adults aged <45 years who are not yet eligible for standard cardiovascular risk screening. This is especially relevant in those with an increased, unfavorable risk factor burden., (© 2015 American Heart Association, Inc.)

Background: The aim of this study was to evaluate whether the addition of ultrasound carotid intima-media thickness (CIMT) measurements and risk categories of plaque help predict incident stroke and cardiovascular disease (CVD) in older adults., Methods: Carotid ultrasound studies were recorded in the multicenter Cardiovascular Health Study. CVD was defined as coronary heart disease plus heart failure plus stroke. Ten-year risk prediction Cox proportional-hazards models for stroke and CVD were calculated using Cardiovascular Health Study-specific coefficients for Framingham risk score factors. Categories of CIMT and CIMT plus plaque were added to Framingham risk score prediction models, and categorical net reclassification improvement (NRI) and Harrell's c-statistic were calculated., Results: In 4,384 Cardiovascular Health Study participants (61% women, 14% black; mean baseline age, 72 ± 5 years) without CVD at baseline, higher CIMT category and the presence of plaque were both associated with higher incidence rates for stroke and CVD. The addition of CIMT improved the ability of Framingham risk score-type risk models to discriminate cases from noncases of incident stroke and CVD (NRI = 0.062, P = .015, and NRI = 0.027, P < .001, respectively), with no further improvement by adding plaque. For both outcomes, NRI was driven by down-classifying those without incident disease. Although the addition of plaque to CIMT did not result in a significant NRI for either outcome, it was significant among those without incident disease., Conclusions: In older adults, the addition of CIMT modestly improves 10-year risk prediction for stroke and CVD beyond a traditional risk factor model, mainly by down-classifying risk in those without stroke or CVD; the addition of plaque to CIMT adds no statistical benefit in the overall cohort, although there is evidence of down-classification in those without events., (Copyright © 2014 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Common carotid artery (CCA) intima-media thickness (IMT) can be measured using ultrasound near to or below the carotid bulb. This might affect associations of IMT with coronary heart disease (CHD) risk factors and events., Methods: IMT measurements were performed near and below the divergence of the CCA bulb in 279 white individuals aged 45 to 54 years free of CHD at baseline and a subset of the Multi-Ethnic Study of Atherosclerosis, a cohort composed of whites, blacks, Chinese, and Hispanic subjects. Participants were followed for an average of 8.2 years. Far wall mean of the maximum IMT (MMaxIMT) and mean of the mean IMT of the right and left CCAs were averaged. Framingham risk factors were used in multivariate linear regression models. Parsimonious Cox proportional regression models included first-time CHD as outcome., Results: Mean of the mean IMT below the bulb was smaller than near the bulb (0.51 ± 0.078 vs 0.56 ± 0.088 mm, P < .001) and had similar associations with risk factors (model R(2) = 0.215 vs 0.186). MMaxIMT below the bulb was associated with risk factors (model R(2) = 0.211), but MMaxIMT near to the bulb was not (R(2) = 0.025). Mean of the mean IMT and MMaxIMT below the bulb were associated with CHD events (hazard ratios, 1.67 [P = .047] and 1.72 [P = .037], respectively) but not when measured near the bulb., Conclusions: CCA IMT measurements made below the bulb are smaller but have more consistent associations with CHD risk factors and outcomes compared with IMT measured near the bulb., (Copyright © 2014 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: The common carotid artery interadventitial diameter is measured on ultrasound images as the distance between the media-adventitia interfaces of the near and far walls. It is associated with common carotid intima-media thickness (IMT) and left ventricular mass and might therefore also have an association with incident stroke., Methods: We studied 6255 individuals free of coronary heart disease and stroke at baseline with mean age of 62.2 years (47.3% men), members of a multiethnic community-based cohort of whites, blacks, Hispanics, and Chinese. Ischemic stroke events were centrally adjudicated. Common carotid artery interadventitial diameter and IMT were measured. Cases with incident atrial fibrillation (n=385) were excluded. Multivariable Cox proportional hazards models were generated with time to ischemic event as outcome, adjusting for risk factors., Results: There were 115 first-time ischemic strokes at 7.8 years of follow-up. Common carotid artery interadventitial diameter was a significant predictor of ischemic stroke (hazard ratio, 1.86; 95% confidence interval, 1.59-2.17 per millimeter) and remained so after adjustment for risk factors and common carotid IMT with a hazard ratio of 1.52/mm (95% confidence interval, 1.22-1.88). Common carotid IMT was not an independent predictor after adjustment (hazard ratio, 0.14; 95% confidence interval, 0.14-1.19)., Conclusions: Although common carotid IMT is not associated with stroke, interadventitial diameter of the common carotid artery is independently associated with first-time incident ischemic stroke even after adjusting for IMT. Our hypothesis that this is in part attributable to the effects of exposure to blood pressure needs confirmation by other studies., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT00063440.

BACKGROUND- Intima-media thickness (IMT) of the common and internal carotid arteries is an established surrogate for atherosclerosis and predicts risk of stroke and myocardial infarction. Often IMT is measured as the average of these 2 arteries; yet, they are believed to result from separate biological mechanisms. The aim of this study was to conduct a family-based genome-wide association study (GWAS) for IMT to identify polymorphisms influencing IMT and to determine if distinct carotid artery segments are influenced by different genetic components. METHODS AND RESULTS- IMT for the common and internal carotid arteries was determined through B-mode ultrasound in 772 Mexican Americans from the San Antonio Family Heart Study. A GWAS using 931219 single-nucleotide polymorphisms was undertaken with 6 internal and common carotid artery IMT phenotypes using an additive measured genotype model. The most robust association detected was for 2 single-nucleotide polymorphisms (rs16983261, rs6113474; P=1.60e(-7)) in complete linkage disequilibrium on chromosome 20p11 for the internal carotid artery near wall, next to the gene PAX1. We also replicated previously reported GWAS regions on chromosomes 19q13 and 7q22. We found no overlapping associations between internal and common carotid artery phenotypes at P<5.0e(-6). The genetic correlation between the 2 carotid IMT arterial segments was 0.51. CONCLUSIONS- This study represents the first large-scale GWAS of carotid IMT in a non-European population and identified several novel loci. We do not detect any shared GWAS signals between common and internal carotid arterial segments, but the moderate genetic correlation implies both common and unique genetic components.

Background: The echolucency of the carotid intima-media is related to increased cardiovascular risk factor levels, morbidity, and mortality. The aim of this study was to assess the effect of statins on the echolucency of the common carotid intima-media in a low-risk population., Methods: Data from the Measuring Effects on Intima-Media Thickness: An Evaluation of Rosuvastatin study were used. Ultrasound images from the far walls of the left and right common carotid arteries were used for evaluation of the echolucency of the carotid intima-media, measured by grayscale median (GSM). Low GSM values reflect echolucent structures, whereas high values reflect echogenic structures. The primary end point was the difference in the annual rate of change in GSM between rosuvastatin and placebo., Results: Two-year change in GSM did not significantly differ between rosuvastatin and placebo in the total population, with a mean difference in the rate of change in GSM of 1.13 (95% confidence interval, -1.00 to 3.25). The effect of rosuvastatin differed across quintiles of baseline GSM values (P for interaction = .01). In the lowest quintile (n = 175) (i.e., in those with the most echolucent intima-media), the difference in the rate of change in GSM between rosuvastatin and placebo was 4.18 (95% confidence interval, -0.23 to 8.58). Increases in GSM were significantly related to decreasing low-density lipoprotein cholesterol levels in the lowest quintile (β = 0.76; 95% confidence interval, 0.26 to 1.25)., Conclusions: Treatment with rosuvastatin did not affect the echolucency of the arterial wall in all low-risk individuals. However, a potential effect of rosuvastatin on the echolucency of the common carotid intima-media is most likely to be found in individuals with echolucent arterial walls at baseline., (Copyright © 2012 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Context: The evidence that measurement of the common carotid intima-media thickness (CIMT) improves the risk scores in prediction of the absolute risk of cardiovascular events is inconsistent., Objective: To determine whether common CIMT has added value in 10-year risk prediction of first-time myocardial infarctions or strokes, above that of the Framingham Risk Score., Data Sources: Relevant studies were identified through literature searches of databases (PubMed from 1950 to June 2012 and EMBASE from 1980 to June 2012) and expert opinion., Study Selection: Studies were included if participants were drawn from the general population, common CIMT was measured at baseline, and individuals were followed up for first-time myocardial infarction or stroke., Data Extraction: Individual data were combined into 1 data set and an individual participant data meta-analysis was performed on individuals without existing cardiovascular disease., Results: We included 14 population-based cohorts contributing data for 45,828 individuals. During a median follow-up of 11 years, 4007 first-time myocardial infarctions or strokes occurred. We first refitted the risk factors of the Framingham Risk Score and then extended the model with common CIMT measurements to estimate the absolute 10-year risks to develop a first-time myocardial infarction or stroke in both models. The C statistic of both models was similar (0.757; 95% CI, 0.749-0.764; and 0.759; 95% CI, 0.752-0.766). The net reclassification improvement with the addition of common CIMT was small (0.8%; 95% CI, 0.1%-1.6%). In those at intermediate risk, the net reclassification improvement was 3.6% in all individuals (95% CI, 2.7%-4.6%) and no differences between men and women., Conclusion: The addition of common CIMT measurements to the Framingham Risk Score was associated with small improvement in 10-year risk prediction of first-time myocardial infarction or stroke, but this improvement is unlikely to be of clinical importance.

Objective: Carotid intima-media thickness (CIMT) is a marker of atherosclerosis that is commonly used to assess the effect of therapeutic interventions. It is currently unclear to what extent biologically implausible values affect treatment effects. We evaluated the impact of biologically implausible CIMT values on the estimated rate of change in CIMT., Methods: Data were used from the METEOR (Measuring Effects on Intima-media Thickness: an Evaluation of Rosuvastatin) trial. METEOR was a randomized, placebo-controlled trial showing that rosuvastatin reduced the 2-year change in CIMT among low-risk individuals with subclinical atherosclerosis. In the main METEOR analysis, the data were analyzed without exclusion of biologically implausible data. In this post-hoc analysis, we constructed twelve definitions to define mildly or extremely biologically implausible values using distance from the interquartile range, median or mean. We evaluated the effect of removing implausible values on the estimated rate of change in CIMT., Results: The percentage of biologically implausible CIMT values ranged from 0.6% to 9.7%, depending on the definition used. Across all definitions, removal of biologically implausible CIMT values marginally reduced standard errors and did not change the primary outcome (i.e., a nonsignificant change in the rosuvastatin group, significant progression in the placebo group, and a statistically significant difference between treatment groups)., Limitation: This study was focussed on the impact of implausible values in the analytical part of a CIMT study. Ultrasound images were not re-examined to determine whether an implausible measurement was due to measurement error or temporal morphological thickening,, Conclusion: Removal of biologically implausible CIMT values marginally decreased the variability of the estimated rate of change in CIMT without having a large impact on the estimated rate of change.

Objective: To assess the added value of multiple imputation (MI) of missing repeated outcomes measures in longitudinal data sets analyzed with linear mixed-effects (LME) models., Study Design and Setting: Data were used from a trial on the effects of Rosuvastatin on rate of change in carotid intima-media thickness (CIMT). The reference treatment effect was derived from a complete data set. Scenarios and proportions of missing values in CIMT measurements were applied and LME analyses were used before and after MI. The added value of MI, in terms of bias and precision, was assessed using the mean-squared error (MSE) of the treatment effects and coverage of the 95% confidence interval., Results: The reference treatment effect was -0.0177 mm/y. The MSEs for LME analysis without and with MI were similar in scenarios with up to 40% missing values. Coverage was large in all scenarios and was similar for LME with and without MI., Conclusion: Our study empirically shows that MI of missing end point data before LME analyses does not increase precision in the estimated rate of change in the end point. Hence, MI had no added value in this setting and standard LME modeling remains the method of choice., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Ultrasound protocols to measure carotid intima-media thickness (CIMT) vary considerably with regard to carotid sites and angles that are assessed. Measurements from the carotid bifurcation and internal carotid artery are thought to be affected by large numbers of missing data. Actual published quantification of completeness rates and the relation with cardiovascular risk factors, however, is scarce. Also, it is currently unknown whether extensive ultrasound protocols including assessment of the carotid bifurcation and internal carotid artery add information in detecting rate of change in CIMT induced by drug therapy. These issues were addressed in this study using data from Measuring Effects on Intima-Media Thickness: An Evaluation of Rosuvastatin (METEOR)., Methods: In METEOR, carotid ultrasound examinations were performed twice before randomization, once each at 6, 12, and 18 months after randomization, and twice after 24 months of study treatment. B-mode ultrasound images were obtained from the near and far walls of the left and right common carotid artery, bifurcation, and internal carotid artery at five predefined angles. Completeness of CIMT data was assessed by carotid site and by angle. A site was considered complete when any of the five angles was measured. The relation between completeness at baseline and cardiovascular risk factors was assessed using logistic regression analyses. Ultrasound protocols with a reduced number of carotid sites and angles were retrospectively constructed, and differences in the rate of change in maximum CIMT between ultrasound protocols were compared., Results: At each visit, CIMT measurements from all 12 carotid sites were available for >94% of the participants. Incompleteness was the highest for near wall of the internal carotid artery and for the extreme angles (60° and 300°). Of 12 risk factors examined, higher body mass index was related to incompleteness. Ultrasound protocols with a reduced number of angles resulted in similar estimates for the differences in rate of change in maximum CIMT. However, reductions in the number of sites gave results in the same direction but with different magnitudes and larger standard errors., Conclusions: High levels of complete data can be obtained with extensive ultrasound protocols that include measurement from the carotid bifurcation and internal carotid artery. A high body mass index contributes to incompleteness of CIMT measurements. Extensive ultrasound protocols are required to obtain the highest precision to observe a treatment effect and to fully cover the degree of atherosclerotic burden., (Copyright © 2012 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Background and Purpose: Carotid artery intima-media thickness (IMT) is a marker of cardiovascular disease associated with incident stroke. We studied whether IMT rate of change is associated with stroke., Methods: We studied 5028 participants of the Multi-Ethnic Study of Atherosclerosis (MESA) comprising white, Chinese, Hispanic, and black participants free of cardiovascular disease. In this MESA IMT progression study, IMT rate of change (mm/year) was the difference in right common carotid artery far wall IMT (mm) divided by the interval between 2 ultrasound examinations (median interval, 32 months). Common carotid artery IMT was measured in a region free of plaque. Cardiovascular risk factors and baseline IMT were determined when IMT rate of change was measured. Multivariable Cox proportional hazards models generated hazard risk ratios (HR) with cardiovascular risk factors, ethnicity, and education level/income as predictors., Results: There were 42 first-time strokes seen during a mean follow-up of 3.22 years (median, 3.0 years). Average age was 64.2 years, with 48% males. In multivariable models, age (HR, 1.05 per year), systolic blood pressure (HR, 1.02 per mm Hg), lower high-density lipoprotein cholesterol levels (HR, 0.96 per mg/dL), and IMT rate of change (HR, 1.23 per 0.05 mm/year; 95% confidence limit, 1.02-1.48) were significantly associated with incident stroke. The upper quartile of IMT rate of change had HR of 2.18 (95% confidence limit, 1.07-4.46) compared to the lower 3 quartiles combined., Conclusions: Common carotid artery IMT progression is associated with incident stroke in this cohort free of prevalent cardiovascular disease and atrial fibrillation at baseline.

Background: Common carotid artery inter-adventitial diameter (IAD) and intima-media thickness (IMT) are measurable by ultrasound. IAD may be associated with left ventricular mass (LV mass) while IMT is a marker of subclinical atherosclerosis. It is not clear if IAD is associated with LV mass after accounting for IMT and traditional cardiovascular risk factors., Methods: IAD and IMT were measured on participants of the Multi-Ethnic Study of Atherosclerosis (MESA) IMT progression study. A total of 5641 of the originally enrolled 6814 MESA participants were studied. LV mass was measured by magnetic resonance imaging. Multivariable linear regression was used with IAD as the outcome and adjustment for risk factors, as well as IMT and LV mass., Results: Traditional cardiovascular risk factors, height, weight and ethnicity were significantly associated with IAD. After adjustment for risk factors, a 1mm difference in IMT was associated with a 1.802mm (95% CI: 1.553, 2.051) higher mean IAD. A 1g difference in LV mass was associated with a 0.006mm (95% CI: 0.005, 0.007) higher mean IAD. After adjusting for cardiovascular risk factors and IMT, a 1g difference in LV mass was associated with a 0.006mm (95% CI: 0.005, 0.008) higher mean IAD for women and 0.004mm (95% CI: 0.003, 0.005) higher IAD for men., Conclusions: Inter-adventitial diameters are associated with left ventricular mass after adjusting for cardiovascular risk factors and IMT. IAD might serve as a surrogate for left ventricular mass and have predictive value for cardiovascular outcomes., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10(-8)). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events.

Carotid ultrasound provides quantitative measurements of carotid intima–media thickness (CIMT) that can be used to assess cardiovascular disease (CVD) risk in individuals and monitor ongoing disease progression and regression in clinical trials. It is non-invasive, rapid, reproducible, and carries no risk. Numerous epidemiological studies have established that CIMT is a marker of subclinical atherosclerosis and is associated with established CVD risk factors and with both prevalent and incident CVD. The use of CIMT in outcome trials as a surrogate or predictor of CVD outcomes is widespread. Carotid ultrasound is being employed to test the efficacy of CVD treatment in order to identify potential useful drugs earlier and to possibly speed regulatory approval. Successive trials have generated lessons learned and applied, with slow but steady improvement in CIMT measurement reproducibility. [ABSTRACT FROM PUBLISHER]