Associations of edge-detected and manual-traced common carotid artery intima-media thickness with incident peripheral artery disease: The Multi-Ethnic Study of Atherosclerosis.

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.

Systemic inflammation and cardiovascular risk factors predict rapid progression of atherosclerosis in rheumatoid arthritis.

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.

Incident stroke is associated with common carotid artery diameter and not common carotid artery intima-media thickness.

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.

Prediction of asymptomatic carotid artery stenosis in the general population: identification of high-risk groups.

BACKGROUND AND PURPOSE: Because of a low prevalence of severe carotid stenosis in the general population, screening for presence of asymptomatic carotid artery stenosis (ACAS) is not warranted. Possibly, for certain subgroups, screening is worthwhile. The present study aims to develop prediction rules for the presence of ACAS (>50% and >70%). METHODS: Individual participant data from 4 population-based cohort studies (Malmö Diet and Cancer Study, Tromsø Study, Carotid Atherosclerosis Progression Study, and Cardiovascular Health Study; totaling 23 706 participants) were pooled. Multivariable logistic regression was performed to determine which variables predict presence of ACAS (>50% and >70%). Calibration and discrimination of the models were assessed, and bootstrapping was used to correct for overfitting. RESULTS: Age, sex, history of vascular disease, systolic and diastolic blood pressure, total cholesterol/high-density lipoprotein ratio, diabetes mellitus, and current smoking were predictors of stenosis (>50% and >70%). The calibration of the model was good confirmed by a nonsignificant Hosmer and Lemeshow test for moderate (P=0.59) and severe stenosis (P=0.07). The models discriminated well between participants with and without stenosis, with an area under the receiver operating characteristic curve corrected for over optimism of 0.82 (95% confidence interval, 0.80-0.84) for moderate stenosis and of 0.87 (95% confidence interval, 0.85-0.90) for severe stenosis. The regression coefficients of the predictors were converted into a score chart to facilitate practical application. CONCLUSIONS: A clinical prediction rule was developed that allows identification of subgroups with high prevalence of moderate (>50%) and severe (>70%) ACAS. When confirmed in comparable cohorts, application of the prediction rule may lead to a reduction in the number needed to screen for ACAS.

Genetics of coronary artery calcification among African Americans, a meta-analysis.

BACKGROUND: Coronary heart disease (CHD) is the major cause of death in the United States. Coronary artery calcification (CAC) scores are independent predictors of CHD. African Americans (AA) have higher rates of CHD but are less well-studied in genomic studies. We assembled the largest AA data resource currently available with measured CAC to identify associated genetic variants. METHODS: We analyzed log transformed CAC quantity (ln(CAC + 1)), for association with ~2.5 million single nucleotide polymorphisms (SNPs) and performed an inverse-variance weighted meta-analysis on results for 5,823 AA from 8 studies. Heritability was calculated using family studies. The most significant SNPs among AAs were evaluated in European Ancestry (EA) CAC data; conversely, the significance of published SNPs for CAC/CHD in EA was queried within our AA meta-analysis. RESULTS: Heritability of CAC was lower in AA (~30%) than previously reported for EA (~50%). No SNP reached genome wide significance (p < 5E-08). Of 67 SNPs with p < 1E-05 in AA there was no evidence of association in EA CAC data. Four SNPs in regions previously implicated in CAC/CHD (at 9p21 and PHACTR1) in EA reached nominal significance for CAC in AA, with concordant direction. Among AA, rs16905644 (p = 4.08E-05) had the strongest association in the 9p21 region. CONCLUSIONS: While we observed substantial heritability for CAC in AA, we failed to identify loci for CAC at genome-wide significant levels despite having adequate power to detect alleles with moderate to large effects. Although suggestive signals in AA were apparent at 9p21 and additional CAC and CAD EA loci, overall the data suggest that even larger samples and an ethnic specific focus will be required for GWAS discoveries for CAC in AA populations.

Prospective study of particulate air pollution exposures, subclinical atherosclerosis, and clinical cardiovascular disease: The Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air).

The Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air) was initiated in 2004 to investigate the relation between individual-level estimates of long-term air pollution exposure and the progression of subclinical atherosclerosis and the incidence of cardiovascular disease (CVD). MESA Air builds on a multicenter, community-based US study of CVD, supplementing that study with additional participants, outcome measurements, and state-of-the-art air pollution exposure assessments of fine particulate matter, oxides of nitrogen, and black carbon. More than 7,000 participants aged 45-84 years are being followed for over 10 years for the identification and characterization of CVD events, including acute myocardial infarction and other coronary artery disease, stroke, peripheral artery disease, and congestive heart failure; cardiac procedures; and mortality. Subcohorts undergo baseline and follow-up measurements of coronary artery calcium using computed tomography and carotid artery intima-medial wall thickness using ultrasonography. This cohort provides vast exposure heterogeneity in ranges currently experienced and permitted in most developed nations, and the air monitoring and modeling methods employed will provide individual estimates of exposure that incorporate residence-specific infiltration characteristics and participant-specific time-activity patterns. The overarching study aim is to understand and reduce uncertainty in health effect estimation regarding long-term exposure to air pollution and CVD.

Associations between C-reactive protein, coronary artery calcium, and cardiovascular events: implications for the JUPITER population from MESA, a population-based cohort study.

BACKGROUND: The JUPITER trial showed that some patients with LDL-cholesterol concentrations less than 3·37 mmol/L (<130 mg/dL) and high-sensitivity C-reactive protein (hsCRP) concentrations of 2 mg/L or more benefit from treatment with rosuvastatin, although absolute rates of cardiovascular events were low. In a population eligible for JUPITER, we established whether coronary artery calcium (CAC) might further stratify risk; additionally we compared hsCRP with CAC for risk prediction across the range of low and high hsCRP values. METHODS: 950 participants from the Multi-Ethnic Study of Atheroslcerosis (MESA) met all criteria for JUPITER entry. We compared coronary heart disease and cardiovascular disease event rates and multivariable-adjusted hazard ratios after stratifying by burden of CAC (scores of 0, 1-100, or >100). We calculated 5-year number needed to treat (NNT) by applying the benefit recorded in JUPITER to the event rates within each CAC strata. FINDINGS: Median follow-up was 5·8 years (IQR 5·7-5·9). 444 (47%) patients in the MESA JUPITER population had CAC scores of 0 and, in this group, rates of coronary heart disease events were 0·8 per 1000 person-years. 74% of all coronary events were in the 239 (25%) of participants with CAC scores of more than 100 (20·2 per 1000 person-years). For coronary heart disease, the predicted 5-year NNT was 549 for CAC score 0, 94 for scores 1-100, and 24 for scores greater than 100. For cardiovascular disease, the NNT was 124, 54, and 19. In the total study population, presence of CAC was associated with a hazard ratio of 4·29 (95% CI 1·99-9·25) for coronary heart disease, and of 2·57 (1·48-4·48) for cardiovascular disease. hsCRP was not associated with either disease after multivariable adjustment. INTERPRETATION: CAC seems to further stratify risk in patients eligible for JUPITER, and could be used to target subgroups of patients who are expected to derive the most, and the least, absolute benefit from statin treatment. Focusing of treatment on the subset of individuals with measurable atherosclerosis could allow for more appropriate allocation of resources. FUNDING: National Institutes of Health-National Heart, Lung, and Blood Institute.

Association between obesity, high-sensitivity C-reactive protein ≥2 mg/L, and subclinical atherosclerosis: implications of JUPITER from the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: High-sensitivity C-reactive protein (hsCRP) levels are closely associated with abdominal obesity, metabolic syndrome, and atherosclerotic cardiovascular disease. The Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) trial has encouraged using hsCRP ≥2 mg/L to guide statin therapy; however, the association of hsCRP and atherosclerosis, independent of obesity, remains unknown. METHODS AND RESULTS: We studied 6760 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). Participants were stratified into 4 groups: nonobese/low hsCRP, nonobese/high hsCRP, obese/low hsCRP, and obese/high hsCRP. Using multivariable logistic and robust linear regression, we described the association with subclinical atherosclerosis, using coronary artery calcium (CAC) and carotid intima-media thickness (cIMT). Mean body mass index was 28.3±5.5 kg/m(2), and median hsCRP was 1.9 mg/L (0.84 to 4.26). High hsCRP, in the absence of obesity, was not associated with CAC and was mildly associated with cIMT. Obesity was strongly associated with CAC and cIMT independently of hsCRP. When obesity and high hsCRP were both present, there was no evidence of multiplicative interaction. Similar associations were seen among 2083 JUPITER-eligible individuals. CONCLUSION: High hsCRP, as defined by JUPITER, was not associated with CAC and was mildly associated with cIMT in the absence of obesity. In contrast, obesity was associated with both measures of subclinical atherosclerosis independently of hsCRP status.

Carotid atherosclerosis predicts incident acute coronary syndromes in rheumatoid arthritis.

OBJECTIVE: The role of atherosclerosis in the acute coronary syndromes (ACS) that occur in patients with rheumatoid arthritis (RA) has not been quantified in detail. We undertook this study to determine the extent to which ACS are associated with carotid atherosclerosis in RA. METHODS: We prospectively ascertained ACS, defined as myocardial infarction, unstable angina, cardiac arrest, or death due to ischemic heart disease, in an RA cohort. We measured carotid atherosclerosis using high-resolution ultrasound. We used Cox proportional hazards models to estimate the association between ACS and atherosclerosis, adjusting for demographic features, cardiovascular (CV) risk factors, and RA manifestations. RESULTS: We performed carotid ultrasound on 636 patients whom we followed up for 3,402 person-years. During this time, 84 patients experienced 121 new or recurrent ACS events, a rate of 3.5 ACS events per 100 patient-years (95% confidence interval [95% CI] 3.0-4.3). Among the 599 patients without a history of ACS, 66 incident ACS events occurred over 3,085 person-years, an incidence of 2.1 ACS events per 100 person-years (95% CI 1.7-2.7). The incidence of new ACS events per 100 patient-years was 1.1 (95% CI 0.6-1.7) among patients without plaque, 2.5 (95% CI 1.7-3.8) among patients with unilateral plaque, and 4.3 (95% CI 2.9-6.3) among patients with bilateral plaque. Covariates associated with incident ACS events independent of atherosclerosis included male sex, diabetes mellitus, and a cumulative glucocorticoid dose of ≥ 20 gm. CONCLUSION: Atherosclerosis is strongly associated with ACS in RA. RA patients with carotid plaque, multiple CV risk factors (particularly diabetes mellitus or hypertension), many swollen joints, and a high cumulative dose of glucocorticoids, as well as RA patients who are men, are at high risk of ACS.

Common carotid intima-media thickness measurements in cardiovascular risk prediction: a meta-analysis.

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.

Common carotid artery intima-media thickness progression as a predictor of stroke in multi-ethnic study of atherosclerosis.

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.

Associations of edge-detected and manual-traced common carotid intima-media thickness measurements with Framingham risk factors: the multi-ethnic study of atherosclerosis.

BACKGROUND AND PURPOSE: Carotid intima-media thickness (IMT) is a marker of cardiovascular disease derived from ultrasound images of the carotid artery. In most outcome studies, human readers identify and trace the key IMT interfaces. We evaluate an alternate approach using automated edge detection. METHODS: We studied a subset of 5640 participants with an average age 61.7 years (48% men) of the Multi-Ethnic Study of Atherosclerosis composed of whites, Chinese, Hispanic, and blacks that are part of the Multi-Ethnic Study of Atherosclerosis IMT progression study. Manual tracing IMT (mt-IMT) and edge-detected IMT (ed-IMT) measurements of the far wall of the common carotid artery served as outcome variables for multivariable linear regression models using Framingham cardiovascular risk factors and ethnicity as independent predictors. RESULTS: Measurements of mt-IMT were obtainable in 99.9% (5633/5640) and measurements of ed-IMT were obtainable in 98.9% (5579/5640) of individuals. Average ed-IMT was 0.19 mm larger than mt-IMT. Inter-reader systematic differences (bias) in IMT measurements were apparent for mt-IMT but not ed-IMT. Based on complete data for 5538 individuals, associations of IMT with risk factors were stronger (P<0.0001) for mt-IMT (model r2, 19.5%) than for ed-IMT (model r2, 18.5%). CONCLUSIONS: We conclude that this edge-detection process generates IMT values equivalent to manually traced ones because it preserves key associations with cardiovascular risk factors. It also decreases inter-reader bias, potentially making it applicable for use in cardiovascular risk assessment.

Coronary calcium as a predictor of coronary events in four racial or ethnic groups.

BACKGROUND: In white populations, computed tomographic measurements of coronary-artery calcium predict coronary heart disease independently of traditional coronary risk factors. However, it is not known whether coronary-artery calcium predicts coronary heart disease in other racial or ethnic groups. METHODS: We collected data on risk factors and performed scanning for coronary calcium in a population-based sample of 6722 men and women, of whom 38.6% were white, 27.6% were black, 21.9% were Hispanic, and 11.9% were Chinese. The study subjects had no clinical cardiovascular disease at entry and were followed for a median of 3.8 years. RESULTS: There were 162 coronary events, of which 89 were major events (myocardial infarction or death from coronary heart disease). In comparison with participants with no coronary calcium, the adjusted risk of a coronary event was increased by a factor of 7.73 among participants with coronary calcium scores between 101 and 300 and by a factor of 9.67 among participants with scores above 300 (P<0.001 for both comparisons). Among the four racial and ethnic groups, a doubling of the calcium score increased the risk of a major coronary event by 15 to 35% and the risk of any coronary event by 18 to 39%. The areas under the receiver-operating-characteristic curves for the prediction of both major coronary events and any coronary event were higher when the calcium score was added to the standard risk factors. CONCLUSIONS: The coronary calcium score is a strong predictor of incident coronary heart disease and provides predictive information beyond that provided by standard risk factors in four major racial and ethnic groups in the United States. No major differences among racial and ethnic groups in the predictive value of calcium scores were detected.

Inter-reader differences in common carotid artery intima-media thickness: implications for cardiovascular risk assessment and vascular age determination.

OBJECTIVES: Far wall common carotid artery intima-media thickness, a surrogate measure of atherosclerosis, requires the tracing of two carotid wall interfaces on ultrasound images: the lumen-intima and media-adventitia. Vascular age is derived from intima-media thickness measurements. We studied how tracing the wall interfaces affects intima-media thickness measurements and estimates of vascular age. METHODS: Five readers made far-wall common carotid intima-media thickness measurements on 26 carotid artery images. Each reader traced lines at the lumen-intima and media-adventitia interfaces. An observer, blinded to reader identity and intima-media thickness values, reviewed the images and estimated the relative location of these lines compared to his judgment of the interface location: +1 for 1 pixel above the interface, 0 at the interface, and -1 if below. The significance of differences was evaluated by analysis of variance. RESULTS: Mean intima-media thickness measurements ranged between 0.57 and 0.78 mm and showed significant differences between readers (P < .009). Differences in carotid intima-media thickness measurements made by the readers were significantly associated with the location of the media-adventitia interfaces (P < .0001) but not the lumen-intima interfaces (P = .07). The intima-media thickness differences corresponded to mean differences in estimated vascular age ranging from 14 to 21 years. CONCLUSIONS: Inter-reader differences in common carotid intima-media thickness measurements are mostly seen for the media-adventitia wall interface and are detectable by an experienced observer. These inter-reader differences affect the use of intima-media thickness measurements for cardiovascular risk evaluation, can cause substantial errors in vascular age estimates, and might be correctable by performing replicate readings of standard image sets.

Imaging of atherosclerosis: carotid intima-media thickness.

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.

Prevalence and progression of subclinical atherosclerosis in younger adults with low short-term but high lifetime estimated risk for cardiovascular disease: the coronary artery risk development in young adults study and multi-ethnic study of atherosclerosis.

BACKGROUND: We hypothesized that individuals with low 10-year but high lifetime cardiovascular disease risk would have a greater burden of subclinical atherosclerosis than those with low 10-year but low lifetime risk. METHODS AND RESULTS: We included 2988 individuals < or = 50 years of age at examination year 15 from the Coronary Artery Risk Development in Young Adults (CARDIA) study and 1076 individuals < or = 50 of age at study entry from the Multi-Ethnic Study of Atherosclerosis (MESA). The 10-year risk and lifetime risk for cardiovascular disease were estimated for each participant, permitting stratification into 3 groups: low 10-year (<10%)/low lifetime (<39%) risk, low 10-year (<10%)/high lifetime risk (> or = 39%), and high 10-year risk (> or = 10%) or diagnosed diabetes mellitus. Baseline levels and change in levels of subclinical atherosclerosis (coronary artery calcium or carotid intima-media thickness) were compared across risk strata. Among participants with low 10-year risk (91% of all participants) in CARDIA, those with a high lifetime risk compared with low lifetime risk had significantly greater common (0.83 versus 0.80 mm in men; 0.79 versus 0.75 mm in women) and internal (0.85 versus 0.80 mm in men; 0.80 versus 0.76 mm in women) carotid intima-media thickness, higher coronary artery calcium prevalence (16.6% versus 9.8% in men; 7.1% versus 2.3% in women), and significantly greater incidence of coronary artery calcium progression (22.3% versus 15.4% in men; 8.7% versus 5.3% in women). Similar results were observed in MESA. CONCLUSIONS: Individuals with low 10-year but high lifetime risk have a greater subclinical disease burden and greater incidence of atherosclerotic progression compared with individuals with low 10-year and low lifetime risk, even at younger ages.

Segment-specific associations of carotid intima-media thickness with cardiovascular risk factors: the Coronary Artery Risk Development in Young Adults (CARDIA) study.

BACKGROUND AND PURPOSE: We propose to study possible differences in the associations between risk factors for cardiovascular disease (myocardial infarction and stroke) and carotid intima-media thickness (IMT) measurements made at 3 different levels of the carotid bifurcation. METHODS: We conducted a cross-sectional study of a cohort of whites and blacks of both genders with a mean age of 45 years. Traditional cardiovascular risk factors were determined in cohort members. Carotid IMT was measured from high-resolution B-mode ultrasound images at 3 levels: the common carotid artery, the carotid artery bulb (bulb), and the internal carotid artery. Associations with risk factors were evaluated by multivariate linear regression analyses. RESULTS: Of 3258 who underwent carotid IMT measurements, common carotid artery, bulb, and internal carotid artery IMT were measured at all 3 separate levels in 3023 (92.7%). A large proportion of the variability of common carotid artery IMT was explained by cardiovascular risk factors (26.8%) but less so for the bulb (11.2%) and internal carotid artery (8.0%). Carotid IMT was consistently associated with age, low-density lipoprotein cholesterol, smoking, and hypertension in all segments. Associations with fasting glucose and diastolic blood pressure were stronger for common carotid artery than for the other segments. Hypertension, diabetes, and current smoking had qualitatively stronger associations with bulb IMT and low-density lipoprotein cholesterol with internal carotid artery IMT. CONCLUSIONS: In our cohort of relatively young white and black men and women, a greater proportion of the variability in common carotid IMT can be explained by traditional cardiovascular risk factors than for the carotid artery bulb and internal carotid arteries.

Prevalence of asymptomatic carotid artery stenosis in the general population: an individual participant data meta-analysis.

BACKGROUND AND PURPOSE: In the discussion on the cost-effectiveness of screening, precise estimates of severe asymptomatic carotid stenosis are vital. Accordingly, we assessed the prevalence of moderate and severe asymptomatic carotid stenosis by age and sex using pooled cohort data. METHODS: We performed an individual participant data meta-analysis (23 706 participants) of 4 population-based studies (Malmö Diet and Cancer Study, Tromsø, Carotid Atherosclerosis Progression Study, and Cardiovascular Health Study). Outcomes of interest were asymptomatic moderate (> or =50%) and severe carotid stenosis (> or =70%). RESULTS: Prevalence of moderate asymptomatic carotid stenosis ranged from 0.2% (95% CI, 0.0% to 0.4%) in men aged <50 years to 7.5% (5.2% to 10.5%) in men aged > or =80 years. For women, this prevalence increased from 0% (0% to 0.2%) to 5.0% (3.1% to 7.5%). Prevalence of severe asymptomatic carotid stenosis ranged from 0.1% (0.0% to 0.3%) in men aged <50 years to 3.1% (1.7% to 5.3%) in men aged > or =80. For women, this prevalence increased from 0% (0.0% to 0.2%) to 0.9% (0.3% to 2.4%). CONCLUSIONS: The prevalence of severe asymptomatic carotid stenosis in the general population ranges from 0% to 3.1%, which is useful information in the discussion on the cost-effectiveness of screening.

Does baseline carotid intima-media thickness modify the effect of rosuvastatin when compared with placebo on carotid intima-media thickness progression? The METEOR study.

BACKGROUND: Many studies have used carotid intima-media thickness (CIMT) measurement to study atherosclerosis and the efficacy of interventions. The placebo-controlled Measuring Effects on intima-media Thickness: an Evaluation Of Rosuvastatin (METEOR) study showed significant reduction in the progression rate of maximum CIMT with 2 years of lipid treatment in asymptomatic individuals with subclinical atherosclerosis. DESIGN: The present post-hoc subgroup analysis of METEOR was carried out to determine whether the effect of rosuvastatin treatment varied according to baseline CIMT level. METHODS: To assess the relationship between efficacy of treatment with rosuvastatin versus placebo and baseline CIMT, we analyzed the effects on the primary CIMT endpoint in participants stratified by baseline quartiles of CIMT (Q1-Q4) using all individuals with a baseline reading and at least one post-baseline CIMT reading. Statistical analysis was carried out using a multilevel repeated-measures linear mixed effects model. RESULTS: In total, 876 participants were included in the analysis. In all quartiles, progression of mean maximum CIMT was significantly slower in rosuvastatin-treated individuals as compared with placebo controls. Although the magnitude of the treatment effect appeared larger in those with the highest baseline CIMT, statistical testing indicated that the magnitude of the treatment effect did not vary significantly with levels of baseline CIMT. CONCLUSION: This subgroup analysis of the METEOR study showed that in middle-aged adults with sub-clinical atherosclerosis, rosuvastatin treatment resulted in significant reduction in mean maximum CIMT progression in four quartiles of baseline CIMT, with no evidence for difference in benefit across levels of baseline CIMT.

Arterial stiffness is associated with regional ventricular systolic and diastolic dysfunction: the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: The pathophysiology of left ventricular (LV) dysfunction, particularly in the setting of a preserved ejection fraction (EF), remains unclear. Few studies have investigated the relationship between arterial compliance and LV function in humans, and none used cardiovascular MRI. METHODS AND RESULTS: We sought to determine whether arterial compliance is related to regional myocardial function among participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Arterial compliance was assessed using carotid ultrasound measurements to calculate the distensibility coefficient (DC) and Young's modulus (YM). Circumferential systolic (SR(S)) and diastolic (SR(E)) strain rates were calculated by harmonic phase (HARP) from tagged MRI. Associations between arterial compliance and indices of ventricular function were adjusted for cardiovascular risk factors. We found a significant association between arterial compliance and SR(S) in all myocardial regions (P<0.05); arterial compliance was also associated with SR(E) in the lateral and septal wall regions (P<0.05). Multiple linear regression analyses demonstrated a direct linear relationship between the carotid artery DC and SR(S) across all LV segments and slices, even after adjustment for cardiovascular risk factors and LV mass. In regression analyses, a significant relationship between arterial compliance and SR(E) in the septal and antero-apical walls was also found and remained significant after multivariable adjustment. CONCLUSIONS: Arterial stiffness is associated with early and asymptomatic impairment of systolic as well as diastolic myocardial function. Further studies are needed to elucidate role of vascular compliance in the development of ventricular dysfunction and failure.