Carotid artery intima-media thickness (IMT) is a marker of cardiovascular disease associated with incident stroke. We study whether IMT rate-of-change is associated with stroke.
Materials and Methods
We studied 5028 participants of the Multi-Ethnic Study of Atherosclerosis (MESA) composed of whites, Chinese, Hispanic and African-Americans free of cardiovascular disease. In this MESA IMT progression study, IMT rate-of-change (mm/year) was the difference in right common carotid artery (CCA) far-wall IMT (mm) divided by the interval between two ultrasound examinations (median interval of 32 months). CCA 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.
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 mmHg), lower HDL cholesterol levels (HR: 0.96 per mg/dL) and IMT rate-of-change (HR 1.23 per 0.05 mm/year; 95% C.L. 1.02, 1.48) were significantly associated with incident stroke. The upper quartile of IMT rate-of-change had an HR of 2.18 (95% C.L.: 1.07, 4.46) compared to the lower three quartiles combined.
Common carotid artery IMT progression is associated with incident stroke in this cohort free of prevalent cardiovascular disease and atrial fibrillation at baseline.
Ultrasonography; Risk Factors; Carotid Arteries; Carotid Intima Media Thickness; stroke
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.
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.
Traditional cardiovascular risk factors, height, weight and ethnicity were significantly associated with IAD. After adjustment for risk factors, a one mm difference in IMT was associated with a 1.802 mm (95% CI: 1.553, 2.051) higher mean IAD. A one gm difference in LV mass was associated with a 0.006 mm (95% CI: 0.005, 0.007) higher mean IAD. LV mass was independently associated with IAD after adjusting for cardiovascular risk factors and IMT. These associations were slightly different for men and women.
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.
carotid arteries; ultrasonics; hypertrophy; magnetic resonance imaging; remodeling; risk factors; left ventricle
Common carotid artery intima-media thickness (IMT), a measure of subclinical cardiovascular disease, changes during the cardiac cycle. The magnitude of this effect and its implications have not been well studied.
Methods and Results
Far-wall IMT measurements of the right common carotid artery were measured at end diastole and peak systole in 5633 individuals from the Multi-Ethnic Study of Atherosclerosis (MESA). Multivariable regression models were generated with end-diastolic IMT, peak-systolic IMT, and change in IMT during the cardiac cycle as dependent variables and traditional cardiovascular risk factors as independent variables. The average age of our population was 61.9 (45 to 84) years. Average change in carotid IMT during the cardiac cycle was 0.041 mm (95% confidence interval: 0.039 to 0.042 mm), with a mean IMT of 0.68 mm. End-diastolic IMT and peak-systolic IMT were similarly associated with risk factors. In a fully adjusted model, change in carotid IMT during the cardiac cycle was associated with ethnicity and pulse pressure (P=0.001) and not age, sex, or other risk factors. Chinese and Hispanics had less of a change in IMT than did non-Hispanic whites. With peak-systolic IMT reference values used as normative data, 31.3% more individuals were classified as being in the upper quartile of IMT and at high risk for cardiovascular disease than would be expected when IMT is measured at end diastole.
Measurable differences in IMT are seen during the cardiac cycle. This affects the interpretation of IMT measurements used for cardiovascular risk assessment, given published normative data with IMT measured at peak systole.
Clinical Trial Registration
URL: www.ClinicalTrials.gov. Unique identifier: NCT00063440. (J Am Heart Assoc. 2012;1:e001420 doi: 10.1161/JAHA.112.001420.)
atherosclerosis; blood pressure; carotid arteries; diastole; epidemiology; risk factors; systole; ultrasonics
Carotid intima-media thickness (IMT) is a sub-clinical marker of atherosclerosis and a strong predictor of stroke. Pericardial fat (PF), the fat depot around the heart, has been associated with several atherosclerosis risk factors. We sought to examine the association between carotid IMT and PF, and to examine whether such an association is independent from common atherosclerosis risk factors including measures of overall adiposity.
Unadjusted and multivariable adjusted linear regression analysis was used to examine associations between common (CCA-IMT) and internal (ICA-IMT) carotid IMT with PF in a random sample of 996 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) who underwent carotid ultrasound and chest CT at baseline examination.
A significant positive correlation was observed between PF and CCA-IMT (r =0.27, P<0.0001) and ICA-IMT (r =0.17, P<0.0001). In an unadjusted sex-specific linear regression analysis, there was a significant association between PF (1-SD difference) and CCA-IMT (mm) in both women (β coefficient (95% CI): 0.06 (0.04, 0.08), P<0.0001) and men (0.03 (0.01, 0.05), P<0.0002), an association that persisted after further adjusting for age and ethnicity (0.02 (+0.00, 0.04), P=0.0120 for women, and 0.02 (+0.00, 0.03), P=0.0208 for men). However, after additional adjustment for atherosclerosis risk factors and either BMI or waist circumference, these relations were no longer significant in either sex. In similar analyses, PF was significantly associated with ICA-IMT in both men (0.11 (0.06, 0.15), P<0.0001) and women (0.08 (0.02, 0.13), P=041). These relations were no longer significant in women in multivariable adjusted models, but persisted in men in all models except after adjusting for age, ethnicity and waist circumference.
In the general population PF is associated with carotid IMT, an association that possibly not independent from markers of overall adiposity or common atherosclerosis risk factors.
The goal of this study was to compare internal carotid artery (ICA) intima-media thickness (IMT) with common carotid artery (CCA) IMT as global markers of cardiovascular disease (CVD).
Cross-sectional measurements of the mean CCA IMT and maximum ICA IMT were made on ultrasound images acquired from the Framingham Offspring cohort (n = 3316; mean age, 58 years; 52.7% women). Linear regression models were used to study the associations of the Framingham risk factors with CCA and ICA IMT. Multivariate logistic regression models and receiver operating characteristic (ROC) curve analysis were used to compare the associations of prevalent CVD with CCA and ICA IMT and determine sensitivity and specificity.
The association between age and the mean CCA IMT corresponded to an increase of 0.007 mm/y; the increase was 0.037 mm/y for the ICA IMT. Framingham risk factors accounted for 28.6% and 27.5% of the variability in the CCA and ICA IMT, respectively. Age and gender contributed 23.5% to the variability of the CCA IMT and 22.5% to that of the ICA IMT, with the next most important factor being systolic blood pressure (1.9%) for the CCA IMT and smoking (1.6%) for the ICA IMT. The CCA IMT and ICA IMT were statistically significant predictors of prevalent CVD, with the ICA IMT having a larger area under the ROC curve (0.756 versus 0.695).
Associations of risk factors with CCA and ICA IMT are slightly different, and both are independently associated with prevalent CVD. Their value for predicting incident cardiovascular events needs to be compared in outcome studies.
atherosclerosis; carotid artery; disease prevalence; intima-media thickness; risk factors
Coronary artery calcium (CAC) and carotid intima-media thickness (IMT) are noninvasive measures of atherosclerosis that consensus panels have recommended as possible additions to risk factor assessment for predicting the probability of cardiovascular disease (CVD) occurrence.
To assess whether maximum carotid IMT or CAC (Agatston Score) is the better predictor of incident CVD.
Design, Setting, Patients
Prospective cohort study of 45–84 year-olds initially free of CVD (n = 6,698) in four ethnic groups, with standardized carotid IMT and CAC measures at baseline, in six field centers of the Multi-Ethnic Study of Atherosclerosis (MESA).
Main Outcome Measure(s)
Incident CVD events (coronary heart disease, stroke, and fatal CVD) over a maximum of 5.3 years of follow-up.
There were 222 CVD events during follow-up. CAC was associated more strongly than carotid IMT with risk of incident CVD. After adjustment for each other and traditional CVD risk factors, the hazard of CVD increased 2.1-fold (95% CI 1.8–2.5) for each standard deviation greater level of log-transformed CAC, versus 1.3-fold (95% CI 1.1–1.4) for each standard deviation greater maximum IMT. For coronary heart disease, the hazard ratios per standard deviation increment were 2.5-fold (95% CI 2.1–3.1) for CAC and 1.2-fold (95% CI 1.0–1.4) for IMT. An ROC analysis also suggested that CAC predicted incident CVD better than IMT did.
Although whether and how to clinically use bio-imaging tests of subclinical atherosclerosis remains a topic of debate, this study found that CAC predicts subsequent CVD events better than does carotid IMT.
Systematic differences between readers or equipment in imaging studies are not uncommon; failure to account for such differences when using Carotid Ultrasonography may introduce bias into associations between carotid intima media thickness (cIMT) and outcomes. We demonstrate the impact of this source of systematic measurement error (SME) using data on 5,521 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) and 661 participants from the Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM). Participants were between 37 and 78 years old. Two outcomes were considered: (1) the effect of HIV infection on cIMT (between study) and (2) the association of cIMT with cardiovascular events (within study). All estimates were adjusted for demographics (age, gender, and ethnicity) and for traditional cardiovascular disease risk factors (smoking, blood pressure, diabetes and cholesterol). When comparing the FRAM and MESA cohorts to estimate the association of HIV infection on common cIMT, accounting for machine and reader variability (between study variability) reduced the difference associated with HIV infection from +0.080 mm (95% Confidence Interval (CI):0.065–0.095) to +0.037 mm (95% CI:0.003 to 0.072) while internal cIMT declined from +0.254 mm (95% CI:0.205–0.303) to +0.192 mm (95% CI:0.076–0.308). Attenuation of the association between cIMT and cardiovascular endpoints occurred when within study reader variability was not accounted for. The effect of SME due to use of multiple readers or machines is most important when comparisons are made between two different study populations. Within-cohort measurement error dilutes the association with events.
Carotid intima media thickness; Measurement error; Bias; Carotid ultrasonography
Increased carotid artery intima-media thickness (IMT) is a non-invasive marker of systemic arterial disease. Increased IMT has been associated with atherosclerosis, abnormal arterial mechanics, myocardial infarction, and stroke. Given evidence of a relationship between cardiovascular health and attention-executive-psychomotor functioning, the purpose of this study was to examine IMT in relation to neuropsychological test performance in patients with a variety of cardiovascular diagnoses.
One hundred and nine participants, ages 55 to 85, underwent neuropsychological assessment and B-mode ultrasound of the left common carotid artery. IMT was calculated using an automated algorithm based on a validated edge-detection technique. The relationship between IMT and measures of language, memory, visual-spatial abilities and attention-executive-psychomotor functioning was modeled using hierarchical linear regression analyses adjusted for age, education, sex, cardiovascular risk, current systolic blood pressure, and history of coronary artery disease (CAD).
Increased IMT was associated with significantly lower performance in the attention-executive-psychomotor domain (IMT beta = −0.26, p < .01), independent of age, education, sex, cardiovascular risk, current systolic blood pressure, and CAD (F(10,100) = 3.61, p < .001). IMT was not significantly related to language, memory, or visual-spatial abilities.
Our findings suggest that, in patients with cardiovascular disease, IMT may be associated with the integrity of frontal subcortical networks responsible for attention-executive-psychomotor performance. Future studies are needed to clarify the mechanisms by which IMT affects cognition and examine potential interactions between increased IMT and other measures of cardiovascular health such as blood pressure variability, cardiac systolic performance, and systemic perfusion.
Cognition; Cardiovascular Diseases; Carotid Arteries; Atherosclerosis; IMT; B-mode Ultrasound
Higher plasma total homocysteine (tHcy) is an established risk factor for cardiovascular disease. The relation between tHcy and carotid artery intima-media thickness (IMT) at the internal carotid artery (ICA)/bulb-IMT and common carotid artery (CCA)-IMT has not been systematically examined. Since the ICA/bulb segment is more prone to plaque formation than the CCA segment, differential associations with tHcy at these sites might suggest mechanisms of tHcy action.
We examined the cross-sectional segment-specific relations of tHcy to ICA/bulb-IMT and CCA-IMT in 2,499 participants from the Framingham Offspring Study, free of cardiovascular disease.
In multivariable linear regression analysis, ICA/bulb-IMT was significantly higher in the fourth tHcy quartile category compared to the other quartile categories, in both the age- and sex-adjusted and in the multivariable-adjusted model (P for trend <0.0001 and <0.01, respectively). We observed a significant age by tHcy interaction for ICA/bulb-IMT (P=0.03) and therefore stratified the analyses by median age (58 years). There was a significant positive trend between tHcy and ICA/bulb-IMT in individuals 58 years of age or older (P-trend <0.01), but not in the younger individuals (P-trend=0.24). For CCA-IMT, no significant trends were observed in any of the analyses.
The segment-specific association between elevated tHcy levels and ICA/bulb-IMT suggests an association between tHcy and plaque formation.
carotid artery; intima-media thickness; homocysteine; atherosclerosis; Framingham Offspring Study
Occupation has been linked to cardiovascular disease (CVD) incidence and mortality, but few studies have investigated occupation in relation to early atherosclerotic disease. This study examined associations between various occupational characteristics and carotid artery intima-media thickness (IMT) in a multi-ethnic sample.
The Multi-Ethnic Study of Atherosclerosis (MESA) recruited 6814 adults aged 45e84 years and free of clinical CVD (response rate 60%, 51% female). Questionnaire data were used to determine occupational group (managerial/professional, sales/office, service, blue-collar), psychosocial job characteristics (ie, job demands, job control) and other sociodemographic information.
Common carotid artery (CCA)-IMT was greater for blue-collar jobs than for management/professional jobs (mean difference=0.012 mm, p=0.049) after adjustment for age, sex, race, place of birth (US or foreign born) and CVD risk factors. Compared to management/professional jobs, internal carotid artery (ICA)-IMT was greater for sales/office, service and blue-collar jobs (mean difference=0.071 mm, p<0.001; 0.057 mm, p=0.009; and 0.110 mm, p<0.001, respectively) after adjustment for age, sex, race and place of birth. The difference between blue-collar jobs and management/professional jobs remained significant after additional adjustment for CVD risk factors, income and education (mean difference=0.048 mm, p=0.045). Higher levels of control at work were associated with thinner CCA-IMT (mean difference=‒0.009 mm, p=0.016, adjusted for age, sex, race and place of birth) but not with ICA-IMT. Job demands had no significant association with IMT.
Blue-collar jobs and low levels of job control were associated with the development of subclinical atherosclerosis.
Carotid intima-media thickness (cIMT) is an independent predictor of cardiovascular risk. Furthermore, ethnicity and gender-specific normative data are required to assess cIMT, which are not available for Andean-Hispanics. In addition, data regarding correlates of subclinical atherosclerosis in ethnic population are needed.
We studied 1448 adults enrolled in a population-based study in Peru. cIMT and carotid plaque were measured with high-resolution ultrasonography. A healthy reference sample (n=472) with no cardiovascular disease, normal weight and normal metabolic parameters was selected to establish normative cIMT values. Correlates of abnormal cIMT and carotid plaque were assessed in the entire population.
In the reference sample, 95th-percentile cIMT values were both age and gender-dependent. In stepwise regression, selected predictors of increasing cIMT were: older age, impaired fasting glucose, diabetes mellitus, higher systolic blood pressure, higher LDL-cholesterol, smoking and male gender. Predictors of carotid plaque included older age, male gender, higher systolic blood pressure, lower diastolic blood pressure and higher LDL-cholesterol. HDL-cholesterol and C-reactive protein were not associated with cIMT or carotid plaque. The lack of association with HDL-cholesterol was confirmed using high performance liquid chromatography.
We present ethnic-specific cutoffs for abnormal cIMT applicable to Andean-Hispanics and correlates of subclinical atherosclerosis in this population. Pending longitudinal studies, our data supports several risk associations seen in other populations and can be used to identify Andean-Hispanics at increased risk for atherosclerotic cardiovascular disease. The lack of association between HDL-C and cIMT or carotid plaque in this population requires further investigation.
carotid intima-media thickness; Andean-Hispanics; definitions; cardiovascular disease; Latin America
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 three different levels of the carotid bifurcation. Methods: Cross-sectional study of a cohort of Whites and African Americans of both genders with mean age 45 years. Traditional cardiovascular risk factors were determined in cohort members. Carotid IMT was measured from high-resolution B-mode ultrasound images at three levels: the common carotid artery (CCA), the carotid artery bulb (Bulb) and the internal carotid artery (ICA). Associations with risk factors were evaluated by multivariate linear regression analyses.
Of 3258 who underwent carotid IMT measurements, CCA, Bulb, and ICA IMT were measured at all three separate levels in 3023 (92.7%). A large proportion of the variability of CCA IMT was explained by cardiovascular risk factors (26.8%) but less so for the Bulb (11.2%) and ICA (8.0%). Carotid IMT was consistently associated with age, LDL-cholesterol, smoking and hypertension in all segments. Associations with fasting glucose and diastolic blood pressure were stronger for CCA than for the other segments. Hypertension, diabetes and current smoking had qualitatively stronger associations with Bulb IMT, and LDL cholesterol with ICA IMT. Conclusion: In our cohort of relatively young white and African-American 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.
Carotid Intimal Medial Thickness; Risk Factors; Carotid Ultrasound
Background and Purpose
Both carotid intima-media thickness (IMT) and obesity are independent determinants of stroke and cardiovascular disease. The prevalence of obesity is higher in Hispanics. The genetic basis of IMT and obesity has not been well-characterized in Caribbean Hispanics. The purpose of this study was to examine the genetic and environmental contributions to IMT and obesity in this population.
The data included 440 subjects from 77 Caribbean Hispanic families. Mean IMT and maximum IMT were measured in the internal carotid artery, common carotid artery, and carotid bifurcation. The total IMT was calculated as the mean value of IMT at all segments. Obesity phenotypes included body mass index (BMI), waist circumference, waist-to-hip ratio (WHR), and skin-fold thickness. Variance component methods were used to estimate age-adjusted and sex-adjusted heritability. Bivariate analyses were conducted to test for genetic and environmental correlations between IMT and obesity.
Heritabilities for IMT ranged from 9% to 40%, with the highest for total maximum IMT and lowest for internal carotid artery maximum IMT. Heritabilities for BMI, waist circumference, WHR, and skin-fold thickness were 44%, 47%, 5%, and 36%, respectively. There were significant genetic, but not environmental, correlations between IMT and BMI, waist circumference, and skin-fold thickness. There were no genetic or environmental correlations between IMT and WHR.
We found a substantial genetic contribution to IMT, BMI, waist circumference, and skin-fold thickness. Obesity and IMT may share common genetic factors. Future gene mapping studies are warranted to identify genes predisposing to IMT and obesity in this population.
carotid arteries; genetics; obesity; stroke
This study investigated the long-term effects of intensive diabetic treatment on the progression of atherosclerosis, measured as common carotid artery intima-media thickness (IMT).
RESEARCH DESIGN AND METHODS
A total of 1,116 participants (52% men) in the Epidemiology of Diabetes Interventions and Complications (EDIC) trial, a long-term follow-up of the Diabetes Control and Complications Trial (DCCT), had carotid IMT measurements at EDIC years 1, 6, and 12. Mean age was 46 years, with diabetes duration of 24.5 years at EDIC year 12. Differences in IMT progression between DCCT intensive and conventional treatment groups were examined, controlling for clinical characteristics, IMT reader, and imaging device.
Common carotid IMT progression from EDIC years 1 to 6 was 0.019 mm less in intensive than in conventional (P < 0.0001), and from years 1 to 12 was 0.014 mm less (P = 0.048); but change from years 6 to 12 was similar (intensive − conventional = 0.005 mm, P = 0.379). Mean A1C levels during DCCT and DCCT/EDIC were strongly associated with progression of IMT, explaining most of the differences in IMT progression between DCCT treatment groups. Albuminuria, older age, male sex, smoking, and higher systolic blood pressure were significant predictors of IMT progression.
Intensive treatment slowed IMT progression for 6 years after the end of DCCT but did not affect IMT progression thereafter (6–12 years). A beneficial effect of prior intensive treatment was still evident 13 years after DCCT ended. These differences were attenuated but not negated after adjusting for blood pressure. These results support the early initiation and continued maintenance of intensive diabetes management in type 1 diabetes to retard atherosclerosis.
To estimate the heritability of carotid intima-media thickness (IMT), a surrogate marker for atherosclerosis, independent of traditional coronary risk factors.
Methods and Results
We performed a classical twin study of carotid IMT using 98 middle-aged male twin pairs, 58 monozygotic (MZ) and 40 dizygotic (DZ) pairs, from the Vietnam Era Twin Registry. All twins were free of overt cardiovascular disease. Carotid IMT was measured by ultrasound. Bivariate and multivariate analyses were used to determine the association between traditional cardiovascular risk factors and carotid IMT. Intraclass correlation coefficients and genetic modeling techniques were used to determine the relative contributions of genes and environment to the variation in carotid IMT. In our sample, the mean of the maximum carotid IMT was 0.75 ± 0.11. Age, systolic blood pressure and HDL were significantly associated with carotid IMT. The intraclass correlation coefficient for carotid IMT was larger in MZ (0.66; 95% confidence interval [CI], 0.62–0.69) than in DZ twins (0.37; 95% CI, 0.29–0.44), and the unadjusted heritability was 0.69 (95% CI, 0.54–0.79). After adjusting for traditional coronary risk factors, the heritability of carotid IMT was slightly reduced but still of considerable magnitude (0.59; 95% CI, 0.39–0.73).
Genetic factors have a substantial influence on the variation of carotid IMT. Most of this genetic effect occurs through pathways independent of traditional coronary risk factors.
heritability; carotid intima-media thickness; twin study; atherosclerosis
Although intima-media thickness (IMT) was increased in several inflammatory diseases, studies investigating whether the inflammatory processes lead to macrovascular alteration with increased IMT in complex regional pain syndrome (CRPS) lack.
Using ultrasound (high-resolution B-mode), we compared bilaterally the IMT of the common carotid artery (CCA-IMT), the radial artery (RA-IMT), the brachial artery (BRA-IMT) and the quotient QRA/CCA, in CRPS type I (n=17), peripheral nerve injury (PNI, n=17) and pain-free controls (PFC, n=22, matched to CRPS by gender, age and traditional cardiovascular risk factors). Statistics: Spearman’s correlation, paired t-test, ANOVA (p<0.05).
Compared to PFC, RA-IMT were significantly increased in both patient groups bilaterally (mean±standard deviation, CRPS affected side vs. PFC dominant side: 0.32±0.08 mm vs. 0.19±0.08 mm, p<0.001; PNI affected side vs. PFC dominant side: 0.27±0.09 mm vs. 0.19±0.08 mm, p< 0.05; CRPS non-affected side vs. PFC non-dominant side: 0.30±0.10 mm vs. 0.19±0.09 mm, p<0.001; PNI non-affected side vs. PFC non-dominant side: 0.25±0.10 mm vs. 0.19±0.09 mm, p<0.05) and QRA/CCA (CRPS affected-side vs. PFC dominant side: 0.49±0.12 vs. 0.30±0.11, p<0.001; PNI affected side vs. PFC dominant side: 0.41±0.10 vs. 0.30±0.11, p<0.05; CRPS non-affected side vs. PFC non-dominant side: 0.43±0.19 vs. 0.30±0.13, p<0.001; PNI non-affected side vs. PFC non-dominant side: 0.39±0.14 vs. 0.30±0.13, p<0.05), and BRA-IMT - only on the affected side in CRPS (CRPS: 0.42±0.06 mm vs. PFC: 0.35±0.08 mm; p<0.05). In CRPS, QRA/CCA was significantly higher on the affected side compared to PNI (p<0.05). However, only CRPS displayed within-group side-to-side differences with a significantly increased RA-IMT and QRA/CCA on the affected side (p<0.05). The CCA-IMT was comparable between all groups and sides.
The increased IMT of peripheral arteries in CRPS suggests ongoing inflammatory process. Until now, only endothelial dysfunction has been reported. The presented morphological macrovascular alterations might explain the treatment resistance of some CRPS patients.
Complex regional pain syndrome; Macrovascular changes; Intima-media thickness; Inflammatory alterations
Atherosclerosis is the leading cause of cardiovascular disease (CVD). Traditional risk factors can be used to identify individuals at high risk for developing CVD and are generally associated with the extent of atherosclerosis; however, substantial numbers of individuals at low or intermediate risk still develop atherosclerosis.
A case-control study was performed using microarray gene expression profiling of peripheral blood from 119 healthy women in the Multi-Ethnic Study of Atherosclerosis cohort aged 50 or above. All participants had low (<10%) to intermediate (10% to 20%) predicted Framingham risk; cases (N = 48) had coronary artery calcium (CAC) score >100 and carotid intima-media thickness (IMT) >1.0 mm, whereas controls (N = 71) had CAC<10 and IMT <0.65 mm. We identified two major expression profiles significantly associated with significant atherosclerosis (odds ratio 4.85; P<0.001); among those with Framingham risk score <10%, the odds ratio was 5.30 (P<0.001). Ontology analysis of the gene signature reveals activation of a major innate immune pathway, toll-like receptors and IL-1R signaling, in individuals with significant atherosclerosis.
Gene expression profiles of peripheral blood may be a useful tool to identify individuals with significant burden of atherosclerosis, even among those with low predicted risk by clinical factors. Furthermore, our data suggest an intimate connection between atherosclerosis and the innate immune system and inflammation via TLR signaling in lower risk individuals.
Intima-media thickness of the common carotid artery (CCA-IMT) is a validated marker of systemic atherosclerosis process. The aim of this study was to evaluate the association between coronary artery disease (CAD), left ventricular hypertrophy (LVH) and CCA-IMT, assessed by Radio Frequency-Quality Intima Media Thickness (RFQIMT) method, the next generation of IMT real-time measurement, based on the direct analysis of the radiofrequency signal and endowed with high accuracy and reproducibility in early detection of arterial wall thickness.
115 patients (76 men, mean age: 65.1 ± 12 years) referred to our department and shown significant (≥ 70% luminal obstruction) stenosis at least in one major epicardial coronary artery were studied. Coronary angiograms were divided for severity and extent of the disease: 79 patients (69%) had one, 24 patients (21%) two, 12 patients (10%) three major epicardial coronary arteries with ≥ 70% stenosis. All patients underwent echocardiography and carotid ultrasound examination, assessed by RF.
Dividing RFQIMT data in tertiles, dyslipidaemia (31 patients with IMT ≥ 1.20 mm vs 16 with IMT = 0.91-1.19 vs 25 with IMT ≤ 0.9, p = 0.004), LVMI (153.5 ± 20.6 g/m2 in IMT ≥ 1.20 mm vs 131.2 ± 8.4 g/m2 in IMT = 0.91-1.19 mm vs 114.3 ± 11.1 g/m2 in IMT ≤ 0.9 mm, P < 0.001) and number of high stenosed coronary arteries (IMT ≥ 1.20 mm population more often showed three vessel diseases than IMT ≤ 0.90 mm one, P < 0.001) seemed to be significantly related to CCA-IMT increases. Furthermore, LVMI is positively related to IMT (r = 0.91; P < 0.001). In a multivariate regression model (R2 = 0.88), RFQIMT remained significantly associated with the dyslipidemia (regression coefficient ± standard error [SE]: 0.057 ± 0.023; p = 0.017), LVMI (regression coefficient ± SE: 0.01 ± 0.001; P < 0.0001) and number of damaged coronaries (regression coefficient ± SE: 0.0174 ± 0.028; P < 0.0001).
RFQIMT is a sophisticated method for carotid ultrasound evaluation. Its evaluation in patients with at least one important major epicardial coronary vessel stenosis would help the accuracy in the general assessment of the number of coronary lesions in these patients.
RFQIMT; LVMI; coronary stenosis; CAD; cardiovascular risk
The use of carotid intima-media thickness (carotid IMT) as a surrogate marker of cardiovascular disease is increasing and the method has now also been applied in several trials investigating patients with type 2 diabetes (T2D). Even though knowledge about methodology is of highest importance in order to make accurate power calculations and analyses of results, no reproducibility studies have been performed in this group of patients. The aim of this study was to quantify the variability of the measurement of carotid IMT in individuals with and without T2D.
We used B-mode ultrasound and a computerized software programme (MIA vascular tools) for analysis of carotid IMT. Measurement of carotid IMT in the far wall of the common carotid artery (CCA) was done for 30 patients with T2D and 30 persons without T2D. The examinations were done by two different sonographers and two different readers on two separate days in order to quantify sonographer-, reader-, and day-to-day variability.
Comparisons of measurement of carotid IMT in CCA between sonographers (sonographer variability) resulted in limits of agreement (LoA) from -0.18 to 0.13 mm for patients with T2D and -0.12 to 0.10 mm for persons without T2D. This means, that a second scanning of the same person with 95% probability would be within this interval of the first scanning. Comparisons between readers assessing the same scanning (reader variability) resulted in LoA from -0.05 to 0.07 mm and -0.04 to 0.05 mm respectively. LoA of the day-to-day variability was -0.13 to 0.18 mm and -0.09 to 0.18 mm respectively. This corresponds to coefficients of variations (CV) of the sonographer- and day-to-day variability of 10% in patients with T2D and 8% in persons without T2D. The CV of the reader variability was 4% and 3% respectively.
Measurement of carotid IMT in the CCA can be determined with good and comparable reproducibility in both patients with T2D and persons without T2D. These findings support the use of carotid IMT in clinical trials with T2D patients and suggest that the numbers of patients needed to detect a given difference will be the same whether the patients have T2D or not.
Background and Purpose
Higher plasma concentrations of the endogenous nitric oxides synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) are associated with increased risk of cardio- and cerebrovascular events and death, presumably by promoting endothelial dysfunction and subclinical atherosclerosis. We hypothesized that plasma ADMA concentrations are positively related to common carotid artery intimal media thickness (CCA-IMT) and to internal carotid (ICA)/bulb-IMT.
We investigated the cross-sectional relations of plasma ADMA with CCA-IMT and ICA/bulb-IMT in 2958 Framingham Heart Study participants (mean age 58 years, 55% women).
In unadjusted analyses, ADMA was positively related to both CCA-IMT (β per SD increment 0.012, p<0.001) and ICA/bulb IMT (β per SD increment 0.059, p<0.001). In multivariable analyses (adjusting for age, sex, systolic blood pressure, antihypertensive treatment, smoking status, diabetes, body mass index (BMI), Total to HDL cholesterol ratio, log C-reactive protein, and serum creatinine), plasma ADMA was not associated with CCA-IMT (p=0.991), but remained significantly and positively related to ICA/bulb IMT (β per SD increment 0.0246, p=0.002).
In our large community-based sample, we observed that higher plasma ADMA concentrations were associated with greater ICA/bulb-IMT but not with CCA-IMT. These data are consistent with the notion that ADMA promotes subclinical atherosclerosis in a site-specific manner, with a greater proatherogenic influence at known vulnerable sites in the arterial tree.
Carotid Intimal Medial Thickness; Endothelium; Epidemiology; Risk Factors; Nitric Oxide
Background and Purpose
Carotid atherosclerosis has been associated with increased risk of stroke, and poorer cognitive performance in older adults. The relation of carotid atherosclerosis to cognitive impairment and MRI indices of ischemia and aging in midlife is less clear.
We studied 1,975 Framingham Offspring Study participants free of stroke and dementia with available carotid ultrasound, brain MRI and neuropsychological testing. We related common and internal carotid artery intima-media thickness (ICA-IMT and CCA-IMT respectively) and internal carotid stenosis (CAS) to large white matter hyperintensity (>1-SD above age-specific mean; LWMH), total brain volume (TCBV), hippocampal volume, silent cerebral infarcts (SCI) and neuropsychological measures of verbal memory, executive function and non-verbal memory measures.
We observed that ICA-IMT, but not CCA-IMT, was associated with higher prevalence of SCI (OR 1.21, 95% CI 1.03–1.43, p<0.05), LWMH (OR 1.19, 95% CI 1.03–1.38, p<0.05), lower TCBV (−0.05 per SD, p<0.05) and poorer performance in verbal memory (−0.06 per SD; p<0.05) and non-verbal memory measures (−0.08 per SD; p<0.01), but not with hippocampal volume. CAS ≥25% was associated with a higher prevalence of LWMH (adjusted OR 1.77, 95% CI 1.25–2.53) and lower TCBV (−0.11 per SD, p=0.042) but not with SCI or hippocampal volume. CAS ≥50% was associated with higher prevalence of SCI (OR 2.53, 95% CI 1.17 – 5.44), LWMH (OR 2.35, 95% CI 1.08–5.13) and poorer performance on executive function (−0.39 per SD; p<0.05) but not with TCBV or hippocampal volume.
Carotid atherosclerosis markers were associated with MRI indices of brain ischemia and aging and with cognitive impairment in a community-based sample of middle-aged adults. Our data suggest that ICA-IMT may be a better marker for cognitive impairment than CCA-IMT.
Carotid atherosclerosis; brain MRI; cognitive performance
Persons with early kidney disease have an increased risk of cardiovascular events and mortality, but the importance of accelerated atherosclerosis in promoting these outcomes is unclear. We therefore explored whether serum cystatin C level is associated with carotid intima-media thickness (IMT) in ambulatory adults without clinical heart disease.
Setting & Participants
We evaluated 6,557 ethnically diverse persons free of clinical cardiovascular disease aged 45 to 84 years at the baseline visit of the Multi-Ethnic Study of Atherosclerosis.
Kidney function was estimated by using 2 methods: serum cystatin C level and estimated glomerular filtration rate, based on creatinine and cystatin C levels.
Outcomes & Measurements
Study outcomes were internal and common carotid IMT, measured by using high-resolution B-mode ultrasound. Multivariate linear and logistic regressions were used to evaluate the independent association of kidney function with carotid IMT.
In unadjusted linear analysis, each SD (0.23 mg/L) greater cystatin C level was associated with 0.091-mm greater internal carotid IMT (P < 0.001), but this association was diminished by 70% after adjustment for age, sex, and race/ethnicity (0.027 mm; P < 0.001) and was no longer significant after adjustment for cardiovascular risk factors (0.005 mm; P = 0.5). Similarly, the strong unadjusted associations of cystatin C level with common carotid IMT disappeared after adjustment. Chronic kidney disease, defined by using either creatinine level or cystatin C–based estimated glomerular filtration rate less than 60 mL/min/1.73 m2, had no independent association with internal and common carotid IMT.
There were few participants with severe kidney disease.
Cystatin C level had no independent association with carotid IMT in a population free of clinical heart disease. This observation suggests that accelerated atherosclerosis is unlikely to be the primary mechanism explaining the independent association of cystatin C level with cardiovascular risk.
Cystatin C; intima-media thickness (IMT); atherosclerosis; cardiovascular diseases; kidney
Epidemiologic studies of the association between alcohol consumption and carotid artery structure have reported conflicting results. We investigated the association between alcohol consumption and carotid atherosclerosis by evaluating the effects of alcohol intake on carotid artery enlargement.
The study population consisted of 4302 community-dwelling Koreans (1577 men and 2725 women) aged 50 years and over. All the subjects had participated in the baseline survey of the Dong-gu Study conducted between 2007 and 2008. Daily alcohol consumption was determined by the number and frequency of alcoholic beverages consumed. We measured common carotid artery intima-media thickness (CCA-IMT), common carotid and bulb IMT (CB-IMT), carotid plaques, and the diameter of the common carotid artery (CCA-diameter) using high-resolution B-mode ultrasonography. We used analysis of covariance and multiple logistic regressions to determine the relationship between alcohol consumption and carotid artery parameters.
CCA-IMT and CB-IMT were negatively correlated with alcohol consumption after controlling for cardiovascular risk factors in men (p for linear trend = 0.009 and = 0.038, respectively). The multivariate-adjusted odds ratio (OR) for carotid plaques was significantly higher in men who consumed >40.0 g/d (OR = 1.81, 95% CI = 1.13-2.91), although a significant positive correlation was observed between alcohol consumption and carotid plaques (p for linear trend = 0.027). Neither carotid IMT nor carotid plaques were correlated with alcohol intake in women. Alcohol intake was positively correlated with CCA-diameter adjusted for carotid IMT and plaques in the multivariate-adjusted model in both sexes (p for linear trend <0.001 for men and 0.020 for women).
The results of our study indicate that alcohol consumption is inversely related to carotid IMT and positively related to carotid plaques in men, but not women. However, alcohol intake is positively associated with CCA-diameter in both men and women. Additional large population-based prospective studies are needed to confirm the effects of alcohol consumption on carotid artery structure.
Increased common carotid intima-media thickness (IMT) is predictive of coronary artery disease and stroke.
In this study, we investigated common carotid IMT by obesity category in a cohort of healthy women without previously known cardiovascular disease.
Design, Setting, Participants, and Main Outcome Measures
One hundred healthy women (aged 24-59 yr) from the general community enrolled in an observational study conducted at an academic medical center participated in the study. B-mode ultrasound imaging of the common carotid arteries was used to measure common carotid IMT in 99 subjects. Fat distribution was determined by computed tomography. Hormonal and inflammatory parameters related to cardiovascular disease and obesity were measured.
IMT was higher in obese [body mass index (BMI) ≥ 30 kg/m2], compared with overweight women (BMI ≥ 25 and < 30 kg/m2) [0.69 mm, interquartile range (IQR) 0.60-0.75 mm] vs. 0.62 mm [IQR 0.56-0.68 mm), P = 0.044] and in comparison with lean women (BMI < 25 kg/m2) [0.69 mm (IQR 0.60-0.75 mm) vs. 0.59 mm (IQR 0.54-0.67 mm), P = 0.016]. In multivariate modeling, age (beta = 0.0050 mm change in IMT per year of age, P = 0.003), smoking (beta = 0.0044 mm change in IMT per pack-year, P = 0.046), and sc abdominal adiposity (beta = 0.00026 mm change in IMT per square centimeter, P = 0.010) were positively associated with IMT, whereas adiponectin (beta =–0.0042 mm change in IMT per milligram per liter, P = 0.045) was negatively associated with IMT. Visceral adiposity (beta = 0.00048 mm change in IMT per square centimeter, P = 0.092) was not significantly associated with IMT after adjusting for age, race, smoking, sc abdominal adiposity, and adiponectin.
Obesity is associated with increased common carotid IMT in young and middle-aged women. Adiponectin and sc abdominal adiposity are associated with carotid IMT in this population.
Carotid intima–media thickness (CIMT) and plaque information can improve coronary heart disease (CHD) risk prediction when added to traditional risk factors (TRF). However, obtaining adequate images of all carotid artery segments (A-CIMT) may be difficult. Of A-CIMT, the common carotid artery intima–media thickness (CCA-IMT) is relatively more reliable and easier to measure. We evaluated whether CCA-IMT is comparable to A-CIMT when added to TRF and plaque information in improving CHD risk prediction in the Atherosclerosis Risk in Communities (ARIC) study.
Methods and results
Ten-year CHD risk prediction models using TRF alone, TRF + A-CIMT + plaque, and TRF + CCA-IMT + plaque were developed for the overall cohort, men, and women. The area under the receiver operator characteristic curve (AUC), per cent individuals reclassified, net reclassification index (NRI), and model calibration by the Grønnesby–Borgan test were estimated. There were 1722 incident CHD events in 12 576 individuals over a mean follow-up of 15.2 years. The AUC for TRF only, TRF + A-CIMT + plaque, and TRF + CCA-IMT + plaque models were 0.741, 0.754, and 0.753, respectively. Although there was some discordance when the CCA-IMT + plaque- and A-CIMT + plaque-based risk estimation was compared, the NRI and clinical NRI (NRI in the intermediate-risk group) when comparing the CIMT models with TRF-only model, per cent reclassified, and test for model calibration were not significantly different.
Coronary heart disease risk prediction can be improved by adding A-CIMT + plaque or CCA-IMT + plaque information to TRF. Therefore, evaluating the carotid artery for plaque presence and measuring CCA-IMT, which is easier and more reliable than measuring A-CIMT, provide a good alternative to measuring A-CIMT for CHD risk prediction.
CIMT; Plaque; Risk prediction