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1.  Serum Carotenoids Reduce Progression of Early Atherosclerosis in the Carotid Artery Wall among Eastern Finnish Men 
PLoS ONE  2013;8(5):e64107.
Several previous epidemiologic studies have shown that high blood levels of carotenoids may be protective against early atherosclerosis, but results have been inconsistent. We assessed the association between atherosclerotic progression, measured by intima-media thickness of the common carotid artery wall, and serum levels of carotenoids.
We studied the effect of carotenoids on progression of early atherosclerosis in a population-based study. The association between concentrations of serum carotenoids, and intima-media thickness of the common carotid artery wall was explored in 840 middle-aged men (aged 46–65 years) from Eastern Finland. Ultrasonography of the common carotid arteries were performed at baseline and 7-year follow-up. Serum levels of carotenoids were analyzed at baseline. Changes in mean and maximum intima media thickness of carotid artery wall were related to baseline serum carotenoid levels in covariance analyses adjusted for covariates.
In a covariance analysis with adjustment for age, ultrasound sonographer, maximum intima media thickness, examination year, body mass index, systolic blood pressure, smoking, physical activity, serum LDL cholesterol, family history of coronary heart disease, antihypertensive medication and serum high sensitivity C-reactive protein, 7-year change in maximum intima media thickness was inversely associated with lycopene (p = 0.005), α-carotene (p = 0.002) and β-carotene (p = 0.019), respectively.
The present study shows that high serum concentrations of carotenoids may be protective against early atherosclerosis.
PMCID: PMC3660262  PMID: 23700460
2.  Carotid-Wall Intima–Media Thickness and Cardiovascular Events 
The New England journal of medicine  2011;365(3):213-221.
Intima–media thickness of the walls of the common carotid artery and internal carotid artery may add to the Framingham risk score for predicting cardiovascular events.
We measured the mean intima–media thickness of the common carotid artery and the maximum intima–media thickness of the internal carotid artery in 2965 members of the Framingham Offspring Study cohort. Cardiovascular-disease outcomes were evaluated for an average follow-up of 7.2 years. Multivariable Cox proportional-hazards models were generated for intima–media thickness and risk factors. We evaluated the reclassification of cardiovascular disease on the basis of the 8-year Framingham risk score category (low, intermediate, or high) after adding intima–media thickness values.
A total of 296 participants had a cardiovascular event. The risk factors of the Framingham risk score predicted these events, with a C statistic of 0.748 (95% confidence interval [CI], 0.719 to 0.776). The adjusted hazard ratio for cardiovascular disease with a 1-SD increase in the mean intima–media thickness of the common carotid artery was 1.13 (95% CI, 1.02 to 1.24), with a nonsignificant change in the C statistic of 0.003 (95% CI, 0.000 to 0.007); the corresponding hazard ratio for the maximum intima–media thickness of the internal carotid artery was 1.21 (95% CI, 1.13 to 1.29), with a modest increase in the C statistic of 0.009 (95% CI, 0.003 to 0.016). The net reclassification index increased significantly after addition of intima–media thickness of the internal carotid artery (7.6%, P<0.001) but not intima–media thickness of the common carotid artery (0.0%, P = 0.99). With the presence of plaque, defined as intima–media thickness of the internal carotid artery of more than 1.5 mm, the net reclassification index was 7.3% (P = 0.01), with an increase in the C statistic of 0.014 (95% CI, 0.003 to 0.025).
The maximum internal and mean common carotid-artery intima–media thicknesses both predict cardiovascular outcomes, but only the maximum intima–media thickness of (and presence of plaque in) the internal carotid artery significantly (albeit modestly) improves the classification of risk of cardiovascular disease in the Framingham Offspring Study cohort. (Funded by the National Heart, Lung, and Blood Institute.)
PMCID: PMC3153949  PMID: 21774709
3.  Carotid Intima-Media Thickness Progression in HIV-Infected Adults Occurs Preferentially at the Carotid Bifurcation and Is Predicted by Inflammation 
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.
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: Unique identifier: NCT01519141
PMCID: PMC3487373  PMID: 23130122
AIDS; carotid arteries; inflammation; atherosclerosis
4.  Common carotid artery intima-media thickness (IMT) progression as a predictor of stroke in MESA (Multi-Ethnic Study of Atherosclerosis) 
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.
PMCID: PMC3202068  PMID: 21885840
Ultrasonography; Risk Factors; Carotid Arteries; Carotid Intima Media Thickness; stroke
5.  Carotid intima-media thickness in young patients with familial hypercholesterolaemia. 
Heart  1996;76(4):321-325.
OBJECTIVE: To assess the extent of early atherosclerotic changes of the carotid arteries in young patients with familial hypercholesterolaemia (FH) detected as increased intima-media thickness (IMT), and to determine the relations between IMT and some clinical and blood variables such as lipid and lipoprotein(a) (Lp(a)) concentration and haemostatic factors. DESIGN: The IMT of the carotid bifurcation, the proximal 1 cm of the internal carotid artery, and the distal 1 cm of the common carotid artery was determined in all subjects using B mode ultrasonography. Blood lipids, fasting glucose, and several haemostatic variables were also analysed. SUBJECTS: 28 patients with FH (12 males and 16 females aged 11 to 27 years, one homozygote, 27 heterozygotes) and 28 sex and age matched normolipidaemic healthy subjects. RESULTS: The mean carotid IMT (the average of six measurements of the maximum far wall IMT in the three carotid segments on each side) was significantly greater in patients with FH than in controls (mean (SD) 0.71 (0.15) v 0.49 (0.08) mm, P < 0.001). In all subjects, the mean IMT was significantly correlated with total cholesterol (r = 0.59), low density lipoprotein (LDL) cholesterol (r = 0.60), triglycerides (r = 0.27), and systolic blood pressure (r = 0.47). No correlation was found between the mean IMT and Lp(a), fibrinogen, tissue plasminogen activator, and plasminogen activator inhibitor 1. CONCLUSIONS: The majority of young patients with FH have a greater intima-media thickness of the carotid arteries than healthy subjects. Since the individual susceptibility of patients with FH to increased LDL cholesterol is different, B mode ultrasonography could provide a useful tool to identify those who are more likely to develop premature atherosclerotic disease.
PMCID: PMC484543  PMID: 8983678
6.  Hyperuricemia and its association with carotid intima-media thickness in hypertensive and non hypertensive patients 
Carotid intima-media thickness (C-IMT) measured noninvasively by ultrasonography is widely used as a marker for increased risk of cardiovascular disease. Also hyperuricemia (HU) is a well recognized risk factor for cardiovascular diseases. The study was designed to assess the relation between hyperuricemia and carotid intima-media thickness C-IMT in patients with and without hypertension (HTN).
This study included 126 patients divided into four groups: (1) Group A, included 59 hypertensive patients with hyperuricemia. (2) Group B, included 29 hypertensive patients without hyperuricemia. (3) Group C, included 17 patients with hyperuricemia and normal blood pressure without history of hypertension. (4) Group D, included 21 control subjects.
We measured carotid intima-media thickness by B-mode ultrasound in the common carotid and internal carotid artery. Routine echocardiography and uric acid level was assessed for all patients.
We found that C-IMT was significantly higher in group A, B and C than group D; and it was significantly higher in group A than B. This means that C-IMT is significantly higher in all hypertensive groups than control group but it was significantly higher in hypertensive hyperuricemia (group A) than those hypertensives without hyperuricemia. We also observed a higher C-IMT in hyperuricemic non hypertensive patients than control group this means that hyperuricemia per se could be a risk factor for atherosclerosis.
Uric acid levels among the whole number of patients included in the study and among the groups with hyperuricemia (group A and C) were positively correlated with the intimal-media thickness (IMT) while there were no correlations in the other two groups without hyperuricemia.
We found that left ventricular hypertrophy (LVH) was significantly higher in hypertensive patients (group A&B) than normotensives (group C&D) either with or without hyperuricemia and this was evident in the hypertensive hyperuricemic patients (group A); but unexpectedly we observed the presence of LVH in the hyperuricemic non hypertensive patients (group C) which was significantly higher than the control group (group D). This means that hyperuricemia is a risk factor for development of LVH hypertrophy independently of hypertension.
Therefore, higher serum uric acid levels are associated with increased C-IMT and left ventricular hypertrophy in hypertensive and even non hypertensive patients. So, early screening for hyperuricemia and lowering serum uric acid levels might be beneficial in slowing progression of atherogenesis.
PMCID: PMC3727469  PMID: 23960588
Hyperuricemia; Hypertension; Left ventricular hypertrophy; Caroid intima mediathickness
7.  Determination of site-specific carotid-intima media thickness: common –carotid artery and carotid bifurcation in hypercholesterolemia patients 
Pakistan Journal of Medical Sciences  2013;29(5):1249-1252.
Objective: To determine site specific carotid intima-media thickness: common–carotid artery and carotid bifurcation in hypercholesterolemia patients as a marker for atherosclerosis.
Methods: Fifty patients with hypercholesterolemia and twenty controls were selected after getting informed consent regarding the investigation of carotid- intima media thickness by B-mode ultrasound. All the patients of hypercholesterolemia with LDL-C > 160mg/dL had family history of coronary artery diseases. This procedure was carried out in the Radiology Department of Dr. Ziauddin Hospitals. Measurement of carotid -intima media thickness, B-mode ultrasonography of common carotid artery, carotid bifurcation and internal carotid artery (left and right carotid arteries) was performed with Toshiba (M# SSA-580A/E2) ultrasound scanner with linear probe. The posterior or far wall of the carotid artery is, the distance between the leading edge first bright line (lumen -intima interface) and the leading edge of the second bright line (media-adventitia interface) of far wall was recorded as intima -media thickness. The average mean of six segments of intima-media thickness was taken as mean CIMT of right and left common carotid, bifurcation and internal carotid arteries.
Results: Maximal CIMT was significantly increased at sites common carotid, carotid bifurcation and internal carotid arteries in fifty patients with hypercholesterolemia as compared to controls. At carotid bifurcation mean of maximal CIMT was (0.9+ 0.3mm). Range of maximum CIMT in hypercholesterolemia patients was (0.8- 3.3mm) and in controls (0.4- 0.8 mm). The thickness was more frequently increased at site of bifurcation.
Conclusions: Carotid intima- media thickness in hypercholesterolemia patients was increased and carotid bifurcation was site that has shown greater increase in intima-media thickness and plaques in these patients predict high risk for atherosclerosis.
PMCID: PMC3858954  PMID: 24353730
CIMT- Carotid- intima media thickness; CCA- Common carotid artery; BULB – Bifurcation of carotid artery; B-mode ultrasound
Echocardiography (Mount Kisco, N.Y.)  2012;10.1111/j.1540-8175.2012.01774.x.
Framingham Risk Scores (FRS) were validated in a mostly Caucasian population. Evaluation of subclinical atherosclerosis by carotid ultrasound may improve ascertainment of risk in non-White populations. This study aimed to evaluate carotid intima-media thickness (cIMT) and carotid plaquing among Mexican Americans, and to correlate these markers with coronary risk factors and the FRS.
Participants (n=141) were drawn from the Cameron County Hispanic Cohort. Carotid artery ultrasound was performed and cIMT measured. Carotid plaque was defined as areas of thickening >50% of the thickness of the surrounding walls. Mean age was 53.1±11.7 years (73.8% female). Most were overweight or obese (88.7%) and more than half (53.2%) had the metabolic syndrome. One third (34.8%) had abnormal carotid ultrasound findings (either cIMT ≥75th percentile for gender and age or presence of plaque). Among those with abnormal carotid ultrasound, the majority were classified as being at low 10-year risk for cardiovascular events. Carotid ultrasound reclassified nearly a third of the cohort as being at high risk. This discordance between 10-year FRS and carotid ultrasound was noted whether risk was assessed for hard coronary events or global risk. Concordance between FRS and carotid ultrasound findings was best when long-term (30-year) risk was assessed and no subject with an abnormal carotid ultrasound was categorized as low risk by the 30-year FRS algorithm.
Integration of carotid ultrasound findings to coronary risk assessments and use of longer term prediction models may provide better risk assessment in this minority population, with earlier initiation of appropriate therapies.
PMCID: PMC3687003  PMID: 22747630
Carotid ultrasound; Subclinical atherosclerosis; Framingham risk score; Minority population; Risk assessment
9.  The Relation Between Hypoalbuminemia and Compliance and Intima-media Thickness of Carotid Artery in Continuous Ambulatory Peritoneal Dialysis Patients 
The aim of this study was to identify the main factor affecting compliance and intimamedia thickness of the elastic common carotid artery in continuous ambulatory peritoneal dialysis patients. Increased intima-media thickness and decreased arterial compliance are associated with elevated risk of cardiovascular disease. This study included 20 patients and 20 age- and sex- matched healthy control subjects. The compliance and intima-media thickness of the right common carotid artery within 1 cm to the bifurcation were measured three times using high-resolution B-mode echocardiography. Blood samples were obtained to measure levels of hemoglobin, phosphorus, total calcium, total CO2, serum albumin, C-reactive protein, serum total cholesterol, LDL- and HDL-cholesterol and triglycerides. We found that the compliance of common carotid artery was lower in the patient group than in the control group. In the patient group, the compliance of common carotid artery was positively correlated with serum albumin concentration, and intima-media thickness of common carotid artery was negatively correlated with serum albumin levels. Stepwise regression analysis showed that serum albumin concentration was independently related to the compliance of common carotid artery, suggesting hypoalbuminemia can independently give deleterious effects on the arterial wall in continuous ambulatory peritoneal dialysis patients.
PMCID: PMC2808580  PMID: 15716606
Peritoneal Dialysis, Continuous Ambulatory; Artery; Compliance; Albumins
10.  C-reactive protein is an independent predictor for carotid artery intima-media thickness progression in asymptomatic younger adults (from the Bogalusa Heart Study) 
Conflicting information exists regarding the association between hsCRP and the progression of early stages of atherosclerosis. The purpose of the study was to investigate the association of high sensitiviy c-reactive protein (hsCRP) along with major cardiovascular (CV) risk factors on early carotid atherosclerosis progression in a large, population-based cohort study.
The study cohort included 839 young adults (aged 24 to 43 years, 70% white, 42% men) enrolled in Bogalusa Heart Study, who in 2001-2002 attended baseline examination with measurements of CV risk factors. Progression of carotid artery intima-media thickness (IMT) was assessed during a mean follow-up of 2.4 years.
Carotid artery IMT progression rates were as follows: composite carotid artery = 9.2 ± 52 μm/y, common carotid artery = 0.0 ± 51 μm/y, carotid bulb = 8.8 ± 103 μm/y, and internal carotid artery = 18.9 ± 81 μm/y. Elevated baseline hsCRP, reflecting an inflammatory state, showed independent association with composite carotid artery IMT progression. Increased age, systolic blood pressure, fasting glucose, LDL cholesterol, and current smoking were other risk associates of carotid artery IMT progression in young adults, indicating an underlying burden on the CV system by multiple risk factors.
In this population-based study, we observed independent categorical association of increased hsCRP with carotid artery IMT progression in young adults. This study underlines the importance of assesssing hsCRP levels along with smoking and traditional CV risk factor profiles in asymptomatic young adults.
PMCID: PMC3264529  PMID: 22208681
Carotid artery intima-media thickness progression; cardiovascular risk; c-reactive protein; epidemiology; young adults
11.  Carotid Intima-Media Thickness Is Associated With Allelic Variants of Stromelysin-1, Interleukin-6, and Hepatic Lipase Genes The Northern Manhattan Prospective Cohort Study 
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.
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).
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.
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.
PMCID: PMC2692936  PMID: 11988625
genetics; interleukin-6; intima-media thickness; lipase; stromelysin 1; ultrasonography
12.  Interaction of workplace demands and cardiovascular reactivity in progression of carotid atherosclerosis: population based study. 
BMJ : British Medical Journal  1997;314(7080):553-558.
OBJECTIVE: To examine the combined influence of workplace demands and changes in blood pressure induced by stress on the progression of carotid atherosclerosis. DESIGN: Population based follow up study of unestablished as well as traditional risk factors for carotid atherosclerosis, ischaemic heart disease, and other outcomes. SETTING: Eastern Finland. SUBJECTS: 591 men aged 42-60 who were fully employed at baseline and had complete data on the measures of carotid atherosclerosis, job demands, blood pressure reactivity, and covariates. MAIN OUTCOME MEASURES: Change in ultrasonographically assessed intima-media thickness of the right and left common carotid arteries from baseline to 4 year follow up. RESULTS: Significant interactions between workplace demands and stress induced reactivity were observed for all measures of progression (P < 0.04). Men with large changes in systolic blood pressure (20 mm Hg or greater) in anticipation of a maximal exercise test and with high job demands had 10-40% greater progression of mean (0.138 v 0.123 mm) and maximum (0.320 v 0.261 mm) intima-media thickness and plaque height (0.347 v 0.264) than men who were less reactive and had fewer job demands. Similar results were obtained after excluding men with prevalent ischaemic heart disease at baseline. Findings were strongest among men with at least 20% stenosis or non-stenotic plaque at baseline. In this subgroup reactive men with high job demands had more than 46% greater atherosclerotic progression than the others. Adjustment for atherosclerotic risk factors did not alter the results. CONCLUSIONS: Men who showed stress induced blood pressure reactivity and who reported high job demands experienced the greatest atherosclerotic progression, showing the association between dispositional risk characteristics and contextual determinants of disease and suggesting that behaviourally evoked cardiovascular reactivity may have a role in atherogenesis.
PMCID: PMC2126071  PMID: 9055713
13.  B-mode ultrasound common carotid artery intima-media thickness and external diameter: cross-sectional and longitudinal associations with carotid atherosclerosis in a large population sample 
Arterial diameter and intima-media thickness (IMT) enlargement may each be related to the atherosclerotic process. Their separate or combined enlargement may indicate different arterial phenotypes with different atherosclerosis risk.
We investigated cross-sectional (baseline 1987–89: n = 7956) and prospective (median follow-up = 5.9 years: n = 4845) associations between baseline right common carotid artery (RCCA) external diameter and IMT with existing and incident carotid atherosclerotic lesions detected by B-mode ultrasound in any right or left carotid segments. Logistic regression models (unadjusted, adjusted for IMT, or adjusted for IMT and risk factors) were used to relate baseline diameter to existing carotid lesions while comparably adjusted parametric survival models assessed baseline diameter associations with carotid atherosclerosis progression (incident carotid lesions). Four baseline arterial phenotypes were categorized as having 1) neither IMT nor diameter enlarged (reference), 2) isolated IMT thickening, 3) isolated diameter enlargement, and 4) enlargement of both IMT and diameter. The association between these phenotypes and progression to definitive carotid atherosclerotic lesions was assessed over the follow-up period.
Each standard deviation increment of baseline RCCA diameter was associated with increasing carotid lesion prevalence (unadjusted odds ratio [OR] = 1.54, 95% confidence interval [CI] = 1.47–1.62) and with progression of carotid atherosclerosis (unadjusted hazards ratio (HR) = 1.37, 95% CI = 1.28–1.46); and the associations remained significant even after adjustment for IMT and risk factors (prevalence OR = 1.11, 95% CI = 1.04–1.18; progression HR = 1.11, 95% CI = 1.03–1.19). Controlling for gender, age and race, persons with both RCCA IMT and diameter in the upper 50th percentiles had the greatest risk of progressing to clearly defined carotid atherosclerotic lesions (all HR = 1.71, 95% CI = 1.47–2.0; men HR = 1.88, 95% CI = 1.48–2.39; women HR = 1.59, 95% CI = 1.31–1.95) while RCCA IMT or diameter alone in the upper 50th percentile produced significantly lower estimated risks.
RCCA IMT and external diameter provide partially overlapping information relating to carotid atherosclerotic lesions. More importantly, the RCCA phenotype of coexistent wall thickening with external diameter enlargement indicates higher atherosclerotic risk than isolated wall thickening or diameter enlargement.
PMCID: PMC2277382  PMID: 18321381
14.  Ultrasonographic measures of cardiovascular disease risk in antiretroviral treatment-naïve individuals with HIV infection 
AIDS (London, England)  2013;27(6):929-937.
To evaluate associations between traditional cardiovascular disease (CVD) risk factors, inflammatory markers, and markers of HIV disease activity with ultrasonographic measures of CVD risk in patients with HIV who are not receiving antiretroviral therapy (ART).
Cross-sectional, baseline evaluation of ART-naïve HIV-infected individuals without known CVD or diabetes mellitus enrolled in a randomized ART treatment trial.
Prior to ART initiation, carotid artery intima-media thickness (CIMT) and brachial artery flow-mediated dilation (FMD) were measured. Additional parameters included CD4 cell count, HIV viral load, body composition, lipoproteins, and inflammatory markers. Associations with common CIMT, bifurcation CIMT, presence of carotid artery lesions, and brachial artery FMD were evaluated.
The 331 enrolled subjects were a median (1st–3rd quartile) of 36 (28–45) years old. Common and bifurcation CIMT values were higher and lesions more prevalent with older age (p <0.001). FMD was lower with older age (p =0.009). Those with a Framingham Risk Score >6%/10 years (N =44) had higher common and bifurcation CIMT (p <0.001), carotid lesion prevalence (p <0.001), and lower FMD (p =0.035). Independent associations with common CIMT were identified for increasing age, height, weight, small LDL particles, and black race; these were similar for bifurcation CIMT. Presence of carotid artery lesions was associated with increasing age, presence of metabolic syndrome, interleukin-6, and lower HIV-1 RNA.
In a contemporary cohort of ART-naive HIV-infected individuals, ultrasonographic measures of CVD risk were more strongly associated with traditional risk factors than CD4 cell counts, HIV replication, or inflammatory markers.
PMCID: PMC3664137  PMID: 23196938
atherosclerosis; carotid arteries; endothelial function; human immunodeficiency virus; inflammation
15.  Risk Factors for the Progression of Intima-Media Thickness of Carotid Arteries: A 2-Year Follow-Up Study in Patients with Newly Diagnosed Type 2 Diabetes 
Diabetes & Metabolism Journal  2013;37(5):365-374.
Intima-media thickness (IMT) of the carotid arteries is known to have a positive correlation with the risk of cardiovascular disease. This study was designed to identify risk factors affecting the progression of carotid IMT in patients with type 2 diabetes mellitus (T2DM).
Patients with newly diagnosed T2DM with carotid IMT measurements were enrolled, and their clinical data and carotid IMT results at baseline and 2 years later were compared.
Of the 171 patients, 67.2% of males and 50.8% of females had abnormal baseline IMT of the left common carotid artery. At baseline, systolic blood pressure, body mass index and smoking in male participants, and fasting plasma glucose and glycated hemoglobin levels in females were significantly higher in patients with abnormal IMT than in those with normal IMT. Low density lipoprotein cholesterol (LDL-C) levels in males and high density lipoprotein cholesterol (HDL-C) levels in females at the 2-year follow-up were significantly different between the nonprogression and the progression groups. Reduction of the United Kingdom Prospective Diabetes Study (UKPDS) 10-year coronary heart disease (CHD) risk score after 2 years was generally higher in the nonprogression group than the progression group.
LDL-C levels in males and HDL-C levels in females at the 2-year follow-up were significantly different between participants with and without progression of carotid IMT. Furthermore, a reduction in the UKPDS 10-year CHD risk score appeared to delay the advancement of atherosclerosis. Therefore, the importance of establishing the therapeutic goal of lipid profiles should be emphasized to prevent the progression of carotid IMT in newly diagnosed T2DM patients.
PMCID: PMC3816138  PMID: 24199166
Atherosclerosis; Carotid artery intima-media thickness; Diabetes mellitus type 2; Risk factors
16.  The Carotid Intima Media Thickness: A Predictor of the Clincal Coronary Events 
Background: The Carotid Intima-Media Thickness (CIMT) is a simple and an inexpensive tool which can be used to assess the cumulative effect of atherosclerotic risk factors and it is also an independent predictor of the future cardiovascular risk. Nevertheless, criticism has been raised throughout the scientific community, based on the observations which indicated a weak correlation between CIMT and coronary atherosclerosis.
It has been suggested by the International Atherosclerosis Project, that the atherosclerotic process occurs at the same time in the carotid, cerebral and the coronary arteries. Measurement of the Carotid Intima-Media Thickness (CIMT) of the Common Carotid Artery (CCA) by B-mode ultrasound was found to be a suitable non-invasive method, to visualize the arterial walls and to monitor the early stages of the atherosclerotic process.
Aim: This study sought to determine the usefulness of B-mode ultrasound as a non-invasive marker to examine the association between CIMT and the extent and the severity of coronary artery disease and its association with the cardiovascular risk factors, if any.
Methods: A cross-sectional study was done among hundred cases and hundred age and sex matched controls who were in the age group of 30-65 years. The cases included those who had undergone coronary angiography. The controls included non-diabetic non-hypertensives with no cardiovascular risk factors. The CIMT was assessed by using a 7MHz linear array transducer. Fasting blood samples were collected for measuring the blood sugar and the lipid profiles.
Results: The statistical analysis was done by using the Student’s t test and ANOVA and a p value of <0.001 was considered to be significant. The Average Carotid Intima Media Thickness (AVCIMT) was higher in the cases (0.90 vs 0.47 in controls, p<0.001, very highly significant). The AVCIMT was found to be higher in those with triple vessel disease (1.00mm)
Conclusion: The easy applicability and the non invasive nature of B-mode ultrasonography make it suitable for use as a surrogate endpoint for measuring the atherosclerotic burden in people with cardiovascular risk factors. Even in this present study, we found a significant association between the extent of carotid atherosclerosis which was measured by B-mode ultrasound, and the presence, its extent, or the lack of coronary atherosclerosis which was documented by coronary angiography.
PMCID: PMC3708203  PMID: 23905108
Atherosclerosis; Carotid; Intima; Coronary
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.
PMCID: PMC3163306  PMID: 19910544
Carotid Intimal Medial Thickness; Risk Factors; Carotid Ultrasound
Carotid artery intima media is a surrogate marker of atherosclerosis and related with ethnicity, age, sex, traditional and non-traditional risk factors. Black ethnicity is related to greater mean and maximum carotid artery intima media thickness when compared to South Asians. Our study was done to find out the mean carotid artery intima media thickness (CAIMT) of normal healthy people of India and Bangladesh, and the relationship of non-modifiable risk factors such as age and sex with CAIMT.
Materials and Methods:
In this observational study, CAIMT of 93 people were examined by B-mode ultrasonography. All subjects underwent a careful interview and clinical, radiological, biochemical examination. Data was analyzed by software statistical package for social sciences (SPSS) (17th version for window).
In our study, the mean CAIMT of healthy subjects including all age group was (754.94 ± 11.96 micron.). Mean CAIMT was higher in age group of 61-80 years (908.75 ± 39.02 micron) than age group of 20-40 years (713.62 ± 16.59 micron) and 41-60 years (745.55 ± 13.05 micron). CAIMT was positively correlated with age (P value <0.001) and sex (P value=0.001).
An aggregated analysis based on this study in different age groups of healthy people may be useful for assessing carotid artery abnormalities as an aid to defining abnormalities and predicting risk of atherosclerosis in individual healthy people living in India and Bangladesh.
PMCID: PMC3354456  PMID: 22629031
Age; carotid artery intima media thickness; ethnicity; normal healthy subjects; sex
Background and Purpose
Carotid intima-media thickness (IMT) is a surrogate marker of subclinical atherosclerosis and a strong predictor of stroke and myocardial infarction. The object of this study was to determine the association between carotid IMT and 702 single nucleotide polymorphisms in 145 genes.
B-mode carotid ultrasound was performed among 408 Hispanics from the Northern Manhattan Study. The common carotid artery IMT and bifurcation IMT were phenotypes of interest. Genetic effects were evaluated by the multivariate regression model adjusting for traditional vascular risk factors. For each individual, we calculated a gene risk score (GRS) defined as the total number of the significant single nucleotide polymorphisms in different genes. Subjects were then divided into 3 GRS categories using the 2 cutoff points: mean GRS ±1 SD.
We identified 6 significant single nucleotide polymorphisms in 6 genes for common carotid artery IMT and 7 single nucleotide polymorphisms in 7 genes for bifurcation IMT using the probability value of 0.005 as the significant level. There were no common significant genes for both phenotypes. The most significant genes were the tissue plasminogen activator (P=0.0005 for common carotid artery IMT) and matrix metallopeptidase-12 genes (P=0.0004 for bifurcation IMT). Haplotype analysis did not yield a more significant result. Subjects with GRS ≥9 had significantly increased IMT than those with GRS ≤5 (P<0.001). GRS was an independent predictor of both common carotid artery IMT (P=2.3×10−9) and bifurcation MT (P=7.2×10−8).
Multiple genes contributed to the variation in carotid IMT. IMT in different carotid segments may be regulated by different sets of susceptibility genes.
PMCID: PMC2676928  PMID: 18787196
atherosclerosis; carotid intima-media thickness; genetics; polymorphism
The composition of atherosclerotic plaque affects the likelihood of an atherothrombotic event but prospective studies relating risk factors to carotid wall and plaque characteristics measured by MRI are lacking. We hypothesized that traditional risk factors are predictors of carotid wall and plaque characteristics measured two decades later.
Methods and Results
A high-resolution contrast-enhanced MRI exam of the carotid artery was performed in 1769 participants. Measures of carotid wall volume and maximum thickness; lipid core presence, volume and maximum area; and fibrous cap thickness were performed centrally. The average age of the sample was 70 years, 57% female, 81% white, and 19% African American. Greater age, total and LDL cholesterol, male gender, white race, diabetes, hypertension and smoking as measured at baseline, were all significant predictors of increased wall volume and maximum wall thickness 18 years later. An analysis of lipid core was restricted to the 1180 participants with maximum wall thickness ≥1.5mm. Lipid core was observed in 569 individuals (weighted percentage = 42%). Baseline age, total and LDL cholesterol were predictors of presence of lipid core 18 years later; however, these relationships were attenuated after adjustment for wall thickness. Concurrently measured LDL was associated with greater lipid core volume, independent of wall thickness. Concurrently measured glucose and body mass index were inversely associated fibrous cap thickness.
Traditional atherosclerosis risk factors are related to increased wall volume and wall thickness two decades later, but they do not discriminate characteristics of plaque composition (core and cap) independent of wall size.
PMCID: PMC2747117  PMID: 19808612
carotid arteries; epidemiology; magnetic resonance imaging; plaque
Clinics (Sao Paulo, Brazil)  2009;64(7):657-664.
To compare common carotid intima-media thickness (IMT) between the two major Brazilian ethnic groups (those of African descent and those of European descent) among individuals with one or more risk factors for atherosclerotic disease.
Two hundred and six patients with one or more risk factors for atherosclerotic disease were evaluated in a cross-sectional study in which their clinical, ethnic and Demographic characteristics were collected. All patients underwent duplex ultrasound examination of their carotid vessels to obtain IMT measurements.
One hundred and fifty-three patients (74.3%) had a carotid IMT greater than 1.0 mm at one or more point of measurement in at least one common carotid artery. There was a significant correlation between older age and mean carotid wall thickness (R=0.479 / P<0.01). Multivariate analysis identified male sex, arterial hypertension and older age as variables associated with increased IMT (P<0.05 for all variables). When IMT was compared between the two ethnic groups in this study, no significant differences were noted. Euro-descendants and Afro-descendants had similar IMT values, even when the groups were stratified by degree of IMT (normal vs. increased) and presence of stroke and/or transient ischemic attack (yes vs. no).
The risk factors associated with increased common carotid artery IMT in Brazilian individuals are similar to those in previously described populations. No differences were observed between the two main Brazilian ethnic groups. Longitudinal studies are required for a better evaluation of the incidence, etiologic factors and evolution of carotid intimomedial thickening in this population.
PMCID: PMC2710439  PMID: 19606242
Intima-media thickness; Carotid; Atherosclerosis; Ethnic groups; Ultrasound
PLoS ONE  2012;7(7):e40606.
The SNP (rs2230500) in PRKCH (the gene encoding protein kinase C η) is associated with ischemic stroke and cerebral hemorrhage in the Chinese population, but the molecular mechanisms are not clear. The aim of the present study is to investigate the association between the SNP and atherosclerosis that is common pathological basis of ischemic stroke and cerebral hemorrhage.
Methodology/Principal Findings
We examined the associations of the SNP with carotid intima-media thickness (CIMT), atherosclerosis diagnosed by CIMT, and factors related with inflammation in the Beijing Child Blood Pressure Study. A total of 1190 subjects participated in the follow-up study. The SNP was genotyped by allele-specific real-time PCR assay. The SNP (rs2230500) in PRKCH was significantly associated with CIMT (in far wall of left common carotid arteries, P = 0.016; in far wall of right common carotid arteries, P = 0.012) under a recessive model after adjustment for age, gender, smoking, and hypertension. The SNP was also significantly associated with complement C3 (P = 0.012) under a dominant model after adjustment for age, gender, and high sensitivity C-reactive protein.
Our data provide evidence that the SNP (rs2230500) in PRKCH decreases the risk of CIMT that is a worthwhile predictor of stroke and complement system possibly mediates this process.
PMCID: PMC3394745  PMID: 22808203
Korean Circulation Journal  2009;39(8):317-321.
Background and Objectives
Carotid artery intima-media thickness (CIMT) has recently been recommended as a non-invasive tool for primary prevention of cardiovascular events; the association between CIMT and adverse cardiovascular events is well-known. We sought to evaluate the prevalence and significance of carotid artery plaque, especially in patients with coronary atherosclerosis.
Subjects and Methods
The study population consisted of 1,705 consecutive patients {933 males (54.7%); mean age, 59.7±10.9 years} who underwent coronary angiography and carotid artery scanning using high-resolution ultrasonography. Carotid plaque was defined as a focal structure encroaching into the arterial lumen by at least 50% of the surrounding IMT value or a thickness >1.2 mm.
Carotid plaque was identified in 30.3% (516/1,705) of the patients. Of patients in whom the plaque location could be evaluated (n=1,027), carotid plaque was located at the common carotid artery {n=64/267 (24.0%)}, carotid bulb {n=194/267 (72.7%)}, and at both sites {n=9/267 (3.4%)}. The prevalence of hypertension (58.5% vs. 45.2%, p<0.001) and diabetes mellitus (30.6% vs. 23.5%, p=0.007) was higher in patients with carotid plaques. The patients with carotid plaques were older (65.4±8.9 years vs. 57.2±10.7 years, p<0.0001), had a thicker CIMT (0.89±0.20 mm vs. 0.77±0.16 mm, p<0.001), and higher fasting blood sugar (FBS) levels (132.1±60.7 mg/dL vs. 121.6±47.1 mg/dL, p<0.001) than those without carotid plaque. Patients with carotid plaque more frequently presented with acute coronary syndrome (32.4% vs. 23.9%, p<0.001) than those without carotid plaque. Significant coronary artery stenosis by coronary angiography (75.4% vs. 58.3%, p<0.001), especially multi-vessel disease (46.3% vs. 27.2%, p<0.001), was more frequent in patients with carotid plaques. On multivariate analysis, old age (≥65 years), hypertension, and increased CIMT (≥1.0 mm) were independent predictors of carotid plaque. Carotid plaque (odds ratio, 1.85; 95% confidence interval, 1.39-2.45; p<0.001) was an independent predictor of multivessel disease based on multivariate regression analysis.
Carotid plaque was common (30.3%) in Korean patients with coronary atherosclerosis, but it is still relatively uncommon compared to Western populations. Carotid plaque was associated with old age, hypertension, and increased IMT, and was an independent predictor of multi-vessel disease.
PMCID: PMC2771847  PMID: 19949637
Carotid arteries; Atherosclerosis; Coronary artery disease
PLoS ONE  2012;7(7):e39519.
Elevated levels of calcium and parathyroid hormone (PTH), characteristics of primary hyperparathyroidism (PHPT), may be associated with cardiovascular morbidity and mortality in the general population. We evaluated the possible vascular effects of these risk factors in patients with mild PHPT by using standard methods and new imaging techniques.
A prospective case-control study.
Subjects and Methods
Forty-eight patients with mild PHPT without any known cardiovascular risk factors were studied at baseline and at one year after parathyroidectomy (PTX) in comparison with 48 healthy age- and gender-matched controls. We measured biochemical variables, augmentation index (AIx), aortic pulse wave velocity (PWVao), radial (IMTrad) and common carotid artery (IMTcca) intima media thicknesses, and the grayscale median (IM-GSM) of the latter.
No significant differences were observed between PHPT patients and controls at baseline for AIx (28.6±12.2 vs. 27.7±12.8%), IMTrad (0.271±0.060 vs. 0.255±0.053 mm), IMTcca (0.688±0.113 vs. 0.680±0.135 mm), or IM-GSM (82.3±17.2 vs. 86.5±15.3), while PWVao was slightly higher in patients (8.68±1.50 vs. 8.13±1.55, p<0.05). Systolic blood pressure (SBP), calcium, and PTH were higher in patients compared with controls, and decreased after PTX, while vitamin D was lower in patients and increased after PTX. While AIx, PWVao, IMTrad, and IMTcca were related to SBP, neither correlated to vitamin D levels. Only PWVao correlated weakly to plasma PTH (r = 0.29, p<0.01) and ionized calcium (r = 0.22, p<0.05) but showed no relation when age and SBP were adjusted for.
We found normal arterial function despite high calcium, PTH, and low vitamin D levels, in patients with mild PHPT without cardiovascular risk factors. The cardiovascular risk associated with low vitamin D and/or high PTH and calcium levels may be explained by their coupling to blood pressure and other risk factors rather than direct effects on arterial structure.
PMCID: PMC3397993  PMID: 22815708
Clinics  2008;63(4):515-520.
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.
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.
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).
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.
PMCID: PMC2664129  PMID: 18719764
Intima-media thickness; Carotid artery; Protocol; Atherosclerosis; Duplex scan

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