Related Articles

OBJECTIVE

The aim of this study was to investigate whether carotid intima-media thickness (IMT) and brachial-ankle pulse wave velocity (baPWV) add value to the Framingham risk score (FRS) in predicting the development of cardiovascular diseases (CVDs) in type 2 diabetic patients with a negative history of CVD.

RESEARCH DESIGN AND METHODS

Type 2 diabetic patients (n = 783) were retrospectively recruited and followed for CVD.

RESULTS

During a 5.4-year follow-up period, 85 incidences of CVD were recorded (10.9%). After adjustment for conventional arterial risk factors, multivariate analysis with the Cox proportional hazards model identified IMT, but not baPWV, as a significant determinant of CVD. In addition, the combination of FRS with IMT, but not with baPWV, improved the prediction of CVD.

CONCLUSIONS

Carotid IMT is a significant predictor of CVD in asymptomatic type 2 diabetic patients, and the combination of FRS and IMT improves the prediction of CVD in these patients.

Objective

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).

Methods

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.

Results

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).

Conclusions

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.

ABSTRACT

Carotid intima-media thickness (CIMT) can be reliably determined in vivo by carotidian ultrasound and is an accessible and reliable method to assess subclinical atherosclerosis. Available epidemiological data showed that CIMT is significantly correlated with future cardiovascular events. However it has limited value to help risk stratification on top of standard risk-derived functions such as Framingham risk score. It is particularly useful in individuals classified as being at intermediate or high risk by the presence of multiple conventional risk factors.

CIMT has a class IIa (LOE: B) reccommendation for cardiovascular risk assessment according to the practice guidelines published in 2010, emphasizing the presence of high risk if the common carotid artery intima–media thickness is above the 75th percentile. There is no indication to measure IMT in patients with full-blown atherosclerotic carotid disease, although carotidian ultrasound still remains a very useful tool to assess the severity of disease even in these subjects.

Progression of CIMT (also associated with increasing age) can be delayed by some drugs (statins, colestipol and niacin) and by risk factors modification. However, there is no consistent data demonstrating a link between progression of CIMT and coronary and cerebral events. Subsequently, studies using CIMT progression as primary outcome to indicate the influence of a certain therapy on cardiovascular risk are inherently misleading as suggested in the recently published ACC/AHA Guidelines.

Aims

To study the utility of risk scores in prediction of subclinical atherosclerosis in young adults.

Methods and results

Participants were 2,204 healthy Finnish adults aged 24–39 years in 2001 from population-based follow-up study Cardiovascular Risk in Young Finns. We examined the performance of the Framingham, Reynolds, SCORE (Systematic Coronary Risk Evaluation), PROCAM, and Finrisk cardiovascular risk scores to predict subclinical atherosclerosis, i.e. carotid artery intima-media thickness(IMT) and plaque, carotid artery distensibility (CDist) and brachial artery flow-mediated dilatation (FMD) 6 years later. In 6-year prediction of high IMT (highest decile or plaque), areas under the receiver operating characteristic curves (AUC) for baseline Finrisk (0.733), SCORE (0.726), PROCAM (0.712) and Reynolds (0.729) risk scores were similar as for Framingham risk score (0.728, P always ≥0.15). All risk scores had similar discrimination in predicting low CDist (lowest decile) (0.652, 0.642, 0.639, 0.658, 0.652 respectively, P always ≥0.41). In prediction of low FMD (lowest decile), Finrisk, PROCAM, Reynolds and Framingham scores had similar AUCs (0.578, 0.594, 0.582, 0.568, P always ≥0.08) and SCORE discriminated slightly better (AUC=0.596, P<0.05). Prediction of subclinical outcomes was consistent when estimated from other statistical measures of discrimination, reclassification, and calibration.

Conclusions

CVD risk scores had equal performance in predicting subclinical atherosclerosis measured by IMT and CDist in young adults. SCORE was more accurate at predicting low FMD than Framingham risk score.

Background

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 study 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 African-Americans that are part of the MESA IMT progression study. Manual tracing IMT (mt_IMT) and edge-detected IMT (ed_IMT) measurements of the far wall of the common carotid artery (CCA) served as outcome variables for multivariable linear regression models using Framingham cardiovascular risk factors and ethnicity as independent predictors.

Results

Measurements of mt_IMT was obtainable in 99.9% (5633/5640) and of ed_IMT 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 on 5538 individuals, associations of IMT with risk factors were stronger (p < 0.0001) for mt_IMT (model r2: 19.5%) than ed_IMT (model r2: 18.5%).

Conclusion

We conclude that this edge-detection process generates IMT values equivalent to manually traced ones since it preserves key associations with cardiovascular risk factors. It also decreases inter-reader bias, potentially making it applicable for use in cardiovascular risk assessment.

Background

Secondary treatment of arteriosclerosis may be applicable for the primary prevention of atherosclerosis in diabetic patients. This prospective, 2-year follow-up study was designed to determine the efficacy and safety of antiplatelet therapy in the prevention of atherosclerosis of diabetic subjects.

Methods

Patients with type 2 diabetes and arteriosclerosis obliterans from the Eastern Asian countries were registered online and randomly assigned either to the aspirin group (81–100 mg/day) or the cilostazol group (100–200 mg/day) in this international, 2-year, prospective follow-up interventional study.

Results

The primary study endpoint was changes in right and left maximum intima-media thickness of the common carotid artery. Secondary endpoints include changes in right and left maximum intima-media thickness of the internal carotid artery; semiquantitative evaluation of cerebral infarction by magnetic resonance imaging; cardiovascular events including sudden death, stroke, transient cerebral ischemic attacks, acute myocardial infarction, angina, and progression of arteriosclerosis obliterans; overall death; withdrawal; and change in ankle-brachial pressure index.

Conclusion

This is the first study to use an online system that was developed in Asian countries for pooling data from an international clinical trial. These findings are expected to help in the prevention of diabetic atherosclerosis and subsequent cardiovascular and cerebrovascular disease.

Background

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.

Methods

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.

Results

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.

Conclusions

The segment-specific association between elevated tHcy levels and ICA/bulb-IMT suggests an association between tHcy and plaque formation.

Background

To compare the predictability of the Framingham Risk Score (FRS), United Kingdom Prospective Diabetes Study (UKPDS) risk engine, and the Systematic Coronary Risk Evaluation (SCORE) for carotid atherosclerosis and peripheral arterial disease in Korean type 2 diabetic patients.

Methods

Among 1,275 registered type 2 diabetes patients in the health center, 621 subjects with type 2 diabetes participated in the study. Well-trained examiners measured the carotid intima-media thickness (IMT), carotid plaque, and ankle brachial index (ABI). The subject's 10-year risk of coronary heart disease was calculated according to the FRS, UKPDS, and SCORE risk scores. These three risk scores were compared to the areas under the curve (AUC).

Results

The odds ratios (ORs) of all risk scores increased as the quartiles increased for plaque, IMT, and ABI. For plaque and IMT, the UKPDS risk score provided the highest OR (95% confidence interval) at 3.82 (2.36, 6.17) and at 6.21 (3.37, 11.45). For ABI, the SCORE risk estimation provided the highest OR at 7.41 (3.20, 17.18). However, no significant difference was detected for plaque, IMT, or ABI (P = 0.839, 0.313, and 0.113, respectively) when the AUCs of the three risk scores were compared. When we graphed the Kernel density distribution of these three risk scores, UKPDS had a higher distribution than FRS and SCORE.

Conclusion

No significant difference was observed when comparing the predictability of the FRS, UKPDS risk engine, and SCORE risk estimation for carotid atherosclerosis and peripheral arterial disease in Korean type 2 diabetic patients.

Background

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.

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 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.

Conclusion

Common carotid artery IMT progression is associated with incident stroke in this cohort free of prevalent cardiovascular disease and atrial fibrillation at baseline.

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.

Results

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.

Context

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.

Objective

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.

Results

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.

Conclusions

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.

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.

Methods

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.

Results

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.

Conclusions

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.

Background

Shear stress gradients and inflammation have been causally associated with atherosclerosis development in carotid bifurcation regions. The mechanism underlying higher levels of carotid intima-media thickness observed among HIV-infected individuals remains unknown.

Methods and Results

We measured carotid intima-media thickness progression and development of plaque in the common carotid, bifurcation region, and internal carotid artery in 300 HIV-infected persons and 47 controls. The median duration of follow-up was 2.4 years. When all segments were included, the rate of intima-media thickness progression was greater in HIV-infected subjects compared with controls after adjustment for traditional risk factors (0.055 vs. 0.024 mm/year, P=0.016). Rate of progression was also greater in the bifurcation region (0.067 vs. 0.025 mm/year, P=0.042) whereas differences were smaller in the common and internal regions. HIV-infected individuals had a greater incidence of plaque compared with controls in the internal (23% vs. 6.4%, P=0.0037) and bifurcation regions (34% vs. 17%, P=0.014). Among HIV-infected individuals, the rate of progression in the bifurcation region was more rapid compared with the common carotid, internal, or mean intima-media thickness; in contrast, progression rates among controls were similar at all sites. Baseline hsCRP was elevated in HIV-infected persons and was a predictor of progression in the bifurcation region.

Conclusions

Atherosclerosis progresses preferentially in the carotid bifurcation region in HIV-infected individuals. hsCRP, a marker of inflammation, is elevated in HIV and is associated with progression in the bifurcation region. These data are consistent with a model in which the interplay between hemodynamic shear stresses and HIV-associated inflammation contribute to accelerated atherosclerosis. (J Am Heart Assoc. 2012;1:jah3-e000422 doi: 10.1161/JAHA.111.000422.)

Clinical Trial Registration

URL: http://clinicaltrials.gov. Unique identifier: NCT01519141

Objective

To quantify the direct and indirect effects of fetal life, childhood, and adult life on risk of cardiovascular disease at age 49-51 years.

Design

Follow up study of the “Newcastle thousand families” birth cohort established in 1947.

Participants

154 men and 193 women who completed a health and lifestyle questionnaire and attended for clinical examination between October 1996 and December 1998.

Main outcome measures

Correlations between mean intima-media thickness of the carotid artery (carotid intima-media thickness) and family history, birth weight, and socioeconomic position around birth; socioeconomic position, growth, illness, and adverse life events in childhood; and adult socioeconomic position, lifestyle, and biological risk markers. Proportions of variance in carotid intima-media thickness that were accounted for by each stage of the lifecourse.

Results

Socioeconomic position at birth and birth weight were negatively associated with carotid intima-media thickness, although only social class at birth in women was a statistically significant covariate independent of adult lifestyle. These early life variables accounted directly for 2.2% of total variance in men and 2.0% in women. More variation in carotid intima-media thickness was explained by adult socioeconomic position and lifestyle, which accounted directly and indirectly for 3.4% of variance in men (95% confidence interval 0.5% to 6.2%) and 7.6% in women (2.1% to 13.0%). Biological risk markers measured in adulthood independently accounted for a further 9.5% of variance in men (2.4% to 14.2%) and 4.9% in women (1.6% to 7.4%).

Conclusions

Adult lifestyle and biological risk markers were the most important determinants of the cardiovascular health of the study members of the Newcastle thousand families cohort at age 49-51 years. The limited overall effect of early life factors may reflect the postwar birth year of this cohort.

Objective

To examine the association between cardiovascular reactivity to a set of psychological stressors and carotid artery intima-media thickness, a marker of subclinical cardiovascular disease in healthy adolescents.

Methods

Participants were 25 boys and 23 girls age 14.2±0.9 years who were measured for heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure reactivity to mirror-tracing, reaction time, speech preparation and ad lib speech tasks and for common carotid artery intima-media thickness. Sequential regression analyses were used to establish the incremental increase in R2 (R2inc) for the prediction of intima-media thickness due to cardiovascular reactivity independent of age, BMI percentile, sex, socioeconomic status, and resting HR or BP.

Results

SBP reactivity while preparing (β= 0.0019, R2inc = 0.09) and giving the speech (β = 0.0014, R2inc = 0.10) and an aggregate reactivity score based on all 4 tasks (β= 0.0026, R2inc = 0.11) independently predicted (p ≤ 0.05) mean carotid artery intima-media thickness. Neither DBP reactivity nor HR reactivity during any task were independent predictors of intima-media thickness.

Conclusion

Stress-induced cardiovascular reactivity, and especially SBP reactivity, is associated with carotid intima-media thickness and the early pathogenesis of cardiovascular disease. The use of an aggregate stress reactivity index provides a more reliable reflection of trait SBP reactivity to psychological stress and increases the confidence that youth with greater cardiovascular stress reactivity may indeed have greater progression of subclinical cardiovascular disease.

OBJECTIVE

To describe and test a practical protocol to measure common carotid intima-media thickness that uses the combined values of two longitudinal examination angles to increase sensitivity.

METHOD

Between February and September 2005, 206 patients underwent duplex scan examination of carotid vessels, and the intima-media thickness of 407 common carotids were measured in three angles: transversal, longitudinal posterolateral, and anterolateral, with three intima-media thickness measurements for each near and far wall. In addition to numbers obtained from the three angles of measurement, a fourth visual perspective was obtained by combining the intima-media thickness results of posterolateral and anterolateral longitudinal views and considering the thickest wall measurement.

RESULTS

Two hundred seventy (66.3%) carotid arteries had an intima-media thickness thicker than 1mm. The mean intima-media thickness values achieved by the different incidences were 1.26±0.6mm (transversal), 1.17±0.54mm (longitudinal anterolateral), and 1.18±0.58mm (longitudinal posterolateral). A significant difference in intima-media thickness measurement values was observed when the three angles of examination plus the combined positive results of both longitudinal angles were compared by ANOVA (P=0.005). The LSD Post-Hoc test determined that the combined longitudinal view results were similar to the transversal views (P=0.28) and had greater intima-media thickness means than isolated anterolateral or posterolateral longitudinal views (P=0.02 and 0.05, respectively).

CONCLUSIONS

The protocol presented is a practical method for obtaining common carotid artery intima-media thickness measurements. The combined longitudinal posterolateral and anterolateral longitudinal views provide a more sensitive evaluation of the inner layers of the carotid walls than isolated longitudinal views.

Maximum carotid artery wall thickness was utilized in a primary prevention population and compared with baseline risk factors. Carotid wall thickness was measured between the blood–intima and media–adventitia interfaces by B-mode ultrasonography using software calipers at points of protrusion. Long-axis measures were confirmed by short-axis assessment. The maximum carotid wall thickness for each subject was divided by age in years to yield an annual accretion rate (called carotid intima–media thickness accretion rate [CIMTAR]). The entire study population was then divided by median CIMTAR to investigate the association with baseline variables used in standard risk assessments with the bifurcated groups. Traditional risk factors such as age, diabetes, smoking, hyperlipidemia, and obesity were not associated with greater than median CIMTAR. Only male gender (P = 0.02) and systolic blood pressure (P = 0.002) in baseline variables were associated with an elevated CIMTAR for the entire population. Among those not taking lipid-lowering therapy at baseline, only systolic blood pressure remained significant (P = 0.0002). Correlations between low-density lipoprotein (LDL) cholesterol level and maximum carotid wall thickness/CIMTAR were weak for the entire population (r = −0.17/r = −0.12, respectively). Measure of maximum carotid wall thickness may select patients earlier for treatment than traditional risk factors. The addition of CIMTAR to risk algorithms may permit a single-point assignation of subsequent vascular risk that is more efficacious than traditional risk factors.

Aims

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.

Conclusion

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.

Background:

The measurement of carotid intima-medial thickness is a well validated measure of cardiovascular risk. Although atherosclerosis occurs in the intima, this arterial layer is not measured alone due to limitation in ultrasound resolution with standard frequency probes.

Methods:

We evaluated the feasibility of using a 55-MHz ultrasound system with high resolution to measure intima thickness in several vascular territories compared to a “standard” frequency probe.

Results:

The intima and medial thickness was measured in the brachial, radial and tibial arteries in 10 healthy subjects and 5 subjects with peripheral arterial disease. The high frequency ultrasound probe showed superior resolution compared to the standard frequency probe allowing for measurement of intima separately from media.

Conclusions:

The intima can be measured independently of media with a high degree of reproducibility using a high frequency probe. This technology may allow for early detection of cardiovascular risk and extend knowledge about the physiological changes in the early atherosclerotic development.

Objectives

To evaluate the association between carotid intima-media thickness (CIMT) and the presence of aortic arch plaques (AP) in a community-based cohort.

Background

Large AP are associated with ischemic stroke. CIMT is a marker of subclinical atherosclerosis and a strong predictor of cardiovascular disease and stroke. The association between CIMT and AP has been studied in stroke patients, but not in the general population. Aim of this study was to investigate this association in an elderly asymptomatic cohort, and the possibility to use CIMT to predict the presence or absence of large AP.

Methods

Stroke-free control subjects from the Aortic Plaque and Risk of Ischemic Stroke (APRIS) Study underwent transesophageal echocardiography and high-resolution B-mode ultrasound of the carotid arteries. CIMT was measured at the common carotid artery, bifurcation and internal carotid artery. The association between CIMT and AP was analyzed by multivariate regression models. Positive and negative predictive values of CIMT for large (≥ 4 mm) AP were calculated.

Results

Among 138 subjects, large AP was present in 35 (25.4%) subjects. Only CIMT at the bifurcation was associated with large AP after adjustment for atherosclerotic risk factors (p=0.007). Positive and negative predictive value for AP ≥ 4 mm of CIMT at the bifurcation above the 75th percentile (≥ 0.95 mm) were 42% and 80%, respectively. Negative predictive value increased to 87% when the median CIMT value (0.82 mm) was used.

Conclusions

CIMT at the bifurcation is independently associated with AP ≥ 4 mm. Its strong negative predictive value for large arch plaque indicates that CIMT may be used as an initial screening test to exclude severe arch atherosclerosis in the general population.

Objectives: This study investigated (a) the hypothesis that stroke patients with aortic atheroma would show comparable atherosclerotic changes in the carotid arteries, which are easily accessible for ultrasound evaluation and (b) the possibility of carotid duplex sonography as a replacement for transoesophageal echocardiography (TEE) for the exclusion or prediction of relevant aortic plaques.

Methods: In 301 consecutive patients (mean age 62 years) with acute cerebral ischaemia, two dimensional ultrasound measurements were taken of common carotid artery intima media thickness (IMT) and maximal plaque area (PA) and the local degree of internal carotid artery (ICA) stenosis were determined. Maximal aortic wall thickness (AWT) was assessed by TEE.

Results: An IMT ⩽0.9 mm yielded a negative predictive value (NPV) of 95.8% for exclusion of aortic atheromas ⩾4 mm and an NPV of 100% for the exclusion of aortic thrombi. However, positive predictive value of IMT >0.9 mm was low (29.6%), increasing only slightly in the presence of carotid plaques (33%). Incidence of aortic thrombi was significantly higher with ⩾50% compared with <50% ICA stenosis (11.3% v 3.9%, respectively). IMT and PA correlated moderately with AWT (r = 0.47, r = 0.53, respectively; p<0.001). Systolic blood pressure, coronary heart disease and peripheral artery disease, increased IMT, and ICA stenosis ⩾50% were independently related to AWT ⩾4 mm.

Conclusions: A high NPV of normal carotid ultrasound does not support routine TEE for the exclusion of complex aortic plaques as a high risk source of cerebral embolism. However, in patients with carotid atherosclerosis, particularly in those with ICA stenosis ⩾50%, TEE should be performed to exclude an additional high risk source for stroke.

BACKGROUND

Cardiovascular disease causes severe morbidity and mortality in type 1 diabetes, although the specific risk factors and whether chronic hyperglycemia has a role are unknown. We examined the progression of carotid intima–media thickness, a measure of atherosclerosis, in a population with type 1 diabetes.

METHODS

As part of the Epidemiology of Diabetes Interventions and Complications (EDIC) study, the long-term follow-up of the Diabetes Control and Complications Trial (DCCT), 1229 patients with type 1 diabetes underwent B-mode ultrasonography of the internal and common carotid arteries in 1994–1996 and again in 1998–2000. We assessed the intima–media thickness in 611 subjects who had been randomly assigned to receive conventional diabetes treatment during the DCCT and in 618 who had been assigned to receive intensive diabetes treatment.

RESULTS

At year 1 of the EDIC study, the carotid intima–media thickness was similar to that in an age- and sex-matched nondiabetic population. After six years, the intima–media thickness was significantly greater in the diabetic patients than in the controls. The mean progression of the intima–media thickness was significantly less in the group that had received intensive therapy during the DCCT than in the group that had received conventional therapy (progression of the intima–media thickness of the common carotid artery, 0.032 vs. 0.046 mm; P=0.01; and progression of the combined intima–media thickness of the common and internal carotid arteries, −0.155 vs. 0.007; P=0.02) after adjustment for other risk factors. Progression of carotid intima–media thickness was associated with age, and the EDIC base-line systolic blood pressure, smoking, the ratio of low-density lipoprotein to high-density lipoprotein cholesterol, and urinary albumin excretion rate and with the mean glycosylated hemoglobin value during the mean duration (6.5 years) of the DCCT.

CONCLUSIONS

Intensive therapy during the DCCT resulted in decreased progression of intima–media thickness six years after the end of the trial.

Background and Objectives

Coronary artery disease (CAD) is a major cause of heart failure associated with left ventricular systolic dysfunction (LVSD). The prognosis of LVSD is significantly influenced by the etiology of heart failure and therefore, differentiation of significant CAD from other etiologies is important. Carotid intima-media thickness (IMT) and plaque are useful predictors for cardiovascular events, including stroke and CAD. The purpose of this study was to evaluate the predictive value of carotid IMT and plaque for the diagnosis of CAD in LVSD patients.

Subjects and Methods

Seventy-three (n= 73, 47 male, 67.6±12.4 years) patients hospitalized for heart failure with severe LVSD were retrospectively enrolled. The severity of CAD was analyzed by the Duke Jeopardy Score system, and carotid IMT and plaque were measured according to the Mannheim Carotid IMT Consensus.

Results

Significant CAD was found in 41 patients (56.1%, CAD group) on coronary angiography. Mean common carotid artery (CCA) IMT (0.74±0.05 mm vs. 1.04±0.04 mm, p<0.01) was significantly higher in the CAD group. Plaque in CCA (6.25% vs. 19.5%, p<0.01) and plaque in bulb (25.0% vs. 60.9%, p<0.001) were significantly higher in the CAD group. Mean CCA IMT {odds ratio (OR) 2.61, 95% confidence interval (CI) 1.134-4.469, p<0.01} and plaque in bulb (OR 4.69, 95% CI 1.702-12.965, p<0.01) were significant predictors for the diagnosis of CAD according to multivariate logistic regression analysis.

Conclusion

In patients with severe LVSD, mean CCA IMT and bulb plaque can be useful additional predictors for the diagnosis of CAD.

Background and Purpose

Atherosclerosis is a complex disorder with hereditary and environmental causes. Carotid artery intima-media wall thickness (IMT) is a useful measure of atherosclerosis. The objective of this study was to determine the association between carotid IMT and functional promoter variants of stromelysin-1 (MMP3: −1612 5A>6A), interleukin-6 (IL6: −174G>C), and hepatic lipase (HL: −480C>T) genes.

Methods

B-mode carotid ultrasound was performed among 87 subjects (mean age, 70 ± 12 years; 55% women; 60% Caribbean-Hispanic, 25% black, and 13% white) from the Northern Manhattan Prospective Cohort Study. Carotid IMT was calculated as a composite measure (mean of the maximum IMT in the bifurcation, the common carotid artery, and the internal carotid artery).

Results

For all polymorphisms, genotype distribution was not significantly different from Hardy-Weinberg equilibrium. The frequencies of the rare alleles were as follows: MMP3 −1612 5A>6A, 0.31 (95% CI, 0.25 to 0.39); IL6 −174 G>C, 0.20 (95% CI, 0.13 to 0.25); and HL −480 C>T, 0.45 (95% CI, 0.35 to 0.50). Carotid IMT in the sample was 0.78±0.18 mm. Subjects with the MMP3 genotype 6A6A had 8% greater mean carotid IMT than the other MMP3 genotypes combined (0.95±0.17 versus 0.87±0.15 mm; P=0.04). Subjects with the IL6 genotype GG had 11% greater IMT (0.85±0.17 versus 0.76±0.16 mm; P=0.03), and those with the HL genotype CC had 13% greater IMT (0.87±20 versus 0.76±0.18 mm; P=0.02) than the other genotypes combined. Adjustment for other risk factors did not change these associations.

Conclusions

Carotid IMT is higher among subjects homozygous for functional variants in genes related to matrix deposition (MMP3 −16126A), inflammation (IL6 −174G), and lipid metabolism (HL −480C). These associations were independent of race-ethnicity and some environmental exposures. Further studies are needed to confirm these genotype-phenotype associations.

Carotid disease is a common finding in patients with coronary artery disease (CAD) and its presence is associated with worse clinical outcomes. Intima-media thickness provides incremental value over traditional risk factors in predicting cardiovascular events; however, it does not predict the absence of CAD or its extent and severity. The presence of carotid plaques is associated with an increased risk of cardiovascular events in patients with CAD regardless of the treatment strategy (medical therapy alone or myocardial revascularization). Hence, we advocate the screening of patients with diagnosed CAD for carotid atherosclerosis. The prognostic impact of ultrasound characteristics of carotid plaques on cardiovascular outcomes of patients with CAD remains controversial.