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1.  Associations of edge detected and manual traced common carotid intima-media thickness (IMT) measurements with Framingham risk factors: the Multi-Ethnic Study of Atherosclerosis 
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.
doi:10.1161/STROKEAHA.110.603449
PMCID: PMC3169166  PMID: 21546477
Ultrasonography; Risk Factors; Carotid Arteries; Carotid Intima Media Thickness
2.  Changes in Carotid Intima-Media Thickness During the Cardiac Cycle: The Multi-Ethnic Study of Atherosclerosis 
Background
Common carotid artery intima-media thickness (IMT), a measure of subclinical cardiovascular disease, changes during the cardiac cycle. The magnitude of this effect and its implications have not been well studied.
Methods and Results
Far-wall IMT measurements of the right common carotid artery were measured at end diastole and peak systole in 5633 individuals from the Multi-Ethnic Study of Atherosclerosis (MESA). Multivariable regression models were generated with end-diastolic IMT, peak-systolic IMT, and change in IMT during the cardiac cycle as dependent variables and traditional cardiovascular risk factors as independent variables. The average age of our population was 61.9 (45 to 84) years. Average change in carotid IMT during the cardiac cycle was 0.041 mm (95% confidence interval: 0.039 to 0.042 mm), with a mean IMT of 0.68 mm. End-diastolic IMT and peak-systolic IMT were similarly associated with risk factors. In a fully adjusted model, change in carotid IMT during the cardiac cycle was associated with ethnicity and pulse pressure (P=0.001) and not age, sex, or other risk factors. Chinese and Hispanics had less of a change in IMT than did non-Hispanic whites. With peak-systolic IMT reference values used as normative data, 31.3% more individuals were classified as being in the upper quartile of IMT and at high risk for cardiovascular disease than would be expected when IMT is measured at end diastole.
Conclusions
Measurable differences in IMT are seen during the cardiac cycle. This affects the interpretation of IMT measurements used for cardiovascular risk assessment, given published normative data with IMT measured at peak systole.
Clinical Trial Registration
URL: www.ClinicalTrials.gov. Unique identifier: NCT00063440. (J Am Heart Assoc. 2012;1:e001420 doi: 10.1161/JAHA.112.001420.)
doi:10.1161/JAHA.112.001420
PMCID: PMC3487346  PMID: 23130162
atherosclerosis; blood pressure; carotid arteries; diastole; epidemiology; risk factors; systole; ultrasonics
3.  Coronary Artery Calcification Compared with Carotid Intima-Media Thickness in Prediction of Cardiovascular Disease Incidence: The Multi-Ethnic Study of Atherosclerosis (MESA) 
Archives of internal medicine  2008;168(12):1333-1339.
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.
doi:10.1001/archinte.168.12.1333
PMCID: PMC2555989  PMID: 18574091
4.  Associations of occupation, job control and job demands with intima-media thickness: The Multi-Ethnic Study of Atherosclerosis (MESA) 
Objectives
Occupation has been linked to cardiovascular disease (CVD) incidence and mortality, but few studies have investigated occupation in relation to early atherosclerotic disease. This study examined associations between various occupational characteristics and carotid artery intima-media thickness (IMT) in a multi-ethnic sample.
Methods
The Multi-Ethnic Study of Atherosclerosis (MESA) recruited 6814 adults aged 45e84 years and free of clinical CVD (response rate 60%, 51% female). Questionnaire data were used to determine occupational group (managerial/professional, sales/office, service, blue-collar), psychosocial job characteristics (ie, job demands, job control) and other sociodemographic information.
Results
Common carotid artery (CCA)-IMT was greater for blue-collar jobs than for management/professional jobs (mean difference=0.012 mm, p=0.049) after adjustment for age, sex, race, place of birth (US or foreign born) and CVD risk factors. Compared to management/professional jobs, internal carotid artery (ICA)-IMT was greater for sales/office, service and blue-collar jobs (mean difference=0.071 mm, p<0.001; 0.057 mm, p=0.009; and 0.110 mm, p<0.001, respectively) after adjustment for age, sex, race and place of birth. The difference between blue-collar jobs and management/professional jobs remained significant after additional adjustment for CVD risk factors, income and education (mean difference=0.048 mm, p=0.045). Higher levels of control at work were associated with thinner CCA-IMT (mean difference=‒0.009 mm, p=0.016, adjusted for age, sex, race and place of birth) but not with ICA-IMT. Job demands had no significant association with IMT.
Conclusions
Blue-collar jobs and low levels of job control were associated with the development of subclinical atherosclerosis.
doi:10.1136/oem.2010.055582
PMCID: PMC3073024  PMID: 20935285
5.  Risk factors and their impact on carotid intima-media thickness in young and middle-aged ischemic stroke patients and controls: The Norwegian Stroke in the Young Study 
BMC Research Notes  2014;7:176.
Background
Vascular morbidity and mortality due to cardiovascular disease (CVD) are high after ischemic stroke at a young age. Data on carotid intima-media thickness (cIMT) as marker of atherosclerosis are scarce for young stroke populations. In this prospective case–control study, we examined cIMT, the burden of vascular risk factors (RF) and their associations among young and middle-aged ischemic stroke patients and controls. We aimed to detect clinical and sub-clinical arterial disease.
Methods
This study was conducted in 150 patients aged 15–60 years and 84 controls free of CVD. We related RF to ultrasonographic B-mode cIMT-measurements obtained from 12 standardized multiangle measurements in the common carotid artery (CCA), carotid bifurcation (BIF) and internal carotid artery (ICA).
Results
RF burden was higher among patients than among controls (p < 0.001). In multivariate analyses of all 234 participants, increased cIMT was associated with age in each carotid segment. Incident stroke was associated with increased ICA-IMT. ICA-IMT increase was associated with a family history of CVD among patients aged 15–44 years, and with RF at mid-age. The overall cIMT difference between patients and controls was 12% for CCA, 17% for BIF and 29% for ICA. Further, increased CCA-IMT was associated with male sex and hypertension. Increased BIF-IMT was associated with dyslipidemia, coronary heart disease and smoking. Increased ICA-IMT was associated with dyslipidemia and stroke.
Conclusions
Ischemic stroke is associated with increased ICA-IMT, related to a family history of CVD among patients aged <45 years, and to increasing RF burden with increasing age. Preventive strategies and aggressive RF treatment are indicated to avoid future cardiovascular events.
Trial registration
NOR-SYS is registered in ClinicalTrials.gov (NCT01597453).
doi:10.1186/1756-0500-7-176
PMCID: PMC3986875  PMID: 24669965
Young stroke; Ischemic stroke; Risk factors; Carotid intima-media thickness; Atherosclerosis; Ultrasound
6.  Variations in Common Carotid Artery Intima-Media Thickness (cIMT) during the Cardiac Cycle: Implications for Cardiovascular Risk Assessment 
Introduction
Common carotid artery (CCA) intima-media thickness (cIMT), a measure of atherosclerosis, varies between peak-systole (PS) and end-diastole (ED). This difference might affect cardiovascular risk assessment.
Materials and methods
IMT measurements of the right and left CCA were synchronized with an electrocardiogram: R-wave for ED and T-wave for PS. IMT was measured in 2930 members of the Framingham Offspring Study. Multivariable regression models were generated with ED-IMT, PS-IMT and change in IMT as dependent variables and Framingham risk factors as independent variables. ED-IMT estimates were compared to the upper quartile of IMT based on normative data obtained at PS.
Results
The average age of our population was 57.9 years. Average difference in IMT during the cardiac cycle was 0.037 mm (95% CI: 0.035–0.038 mm). ED-IMT and PS-IMT had similar associations with Framingham risk factors (total R2= 0.292 versus 0.275) and were significantly associated with all risk factors. In a fully adjusted multivariable model, a thinner IMT at peak-systole was associated with pulse pressure (p < 0.0001), LDL-cholesterol (p = 0.0064), age (p = 0.046), and no other risk factors. Performing ED-IMT measurements while using upper quartile PS-IMT normative data lead to inappropriately increasing by 42.1% the number of individuals in the fourth IMT quartile (high cardiovascular risk category).
Conclusion
The difference in IMT between peak-systole and end-diastole is associated with pulse pressure, LDL-cholesterol, and age. In our study, mean IMT difference during the cardiac cycle lead to an overestimation by 42.1% of individuals at high risk for cardiovascular disease.
doi:10.1016/j.echo.2012.05.007
PMCID: PMC3544292  PMID: 22721828
Ultrasonics; Risk Factors; Carotid Arteries; Blood Pressure; systole; diastole
7.  Carotid intima-media thickness progression to predict cardiovascular events in the general population (the PROG-IMT collaborative project): a meta-analysis of individual participant data 
Lancet  2012;379(9831):2053-2062.
Summary
Background
Carotid intima-media thickness (cIMT) is related to the risk of cardiovascular events in the general population. An association between changes in cIMT and cardiovascular risk is frequently assumed but has rarely been reported. Our aim was to test this association.
Methods
We identified general population studies that assessed cIMT at least twice and followed up participants for myocardial infarction, stroke, or death. The study teams collaborated in an individual participant data meta-analysis. Excluding individuals with previous myocardial infarction or stroke, we assessed the association between cIMT progression and the risk of cardiovascular events (myocardial infarction, stroke, vascular death, or a combination of these) for each study with Cox regression. The log hazard ratios (HRs) per SD difference were pooled by random effects meta-analysis.
Findings
Of 21 eligible studies, 16 with 36 984 participants were included. During a mean follow-up of 7·0 years, 1519 myocardial infarctions, 1339 strokes, and 2028 combined endpoints (myocardial infarction, stroke, vascular death) occurred. Yearly cIMT progression was derived from two ultrasound visits 2–7 years (median 4 years) apart. For mean common carotid artery intima-media thickness progression, the overall HR of the combined endpoint was 0·97 (95% CI 0·94–1·00) when adjusted for age, sex, and mean common carotid artery intima-media thickness, and 0·98 (0·95–1·01) when also adjusted for vascular risk factors. Although we detected no associations with cIMT progression in sensitivity analyses, the mean cIMT of the two ultrasound scans was positively and robustly associated with cardiovascular risk (HR for the combined endpoint 1·16, 95% CI 1·10–1·22, adjusted for age, sex, mean common carotid artery intima-media thickness progression, and vascular risk factors). In three studies including 3439 participants who had four ultrasound scans, cIMT progression did not correlate between occassions (reproducibility correlations between r=−0·06 and r=−0·02).
Interpretation
The association between cIMT progression assessed from two ultrasound scans and cardiovascular risk in the general population remains unproven. No conclusion can be derived for the use of cIMT progression as a surrogate in clinical trials.
Funding
Deutsche Forschungsgemeinschaft.
doi:10.1016/S0140-6736(12)60441-3
PMCID: PMC3918517  PMID: 22541275
8.  Carotid artery plaque and progression of coronary artery calcium: the Multi-Ethnic Study of Atherosclerosis 
Background
Carotid and coronary atherosclerosis are associated to each other in imaging and autopsy studies. We evaluated whether carotid artery plaque seen on carotid ultrasound can predict incident coronary artery calcification (CAC).
Materials and Methods
We repeated Agatston calcium score measurements in 5445 participants of the Multi-Ethnic Study of Atherosclerosis (MESA) (mean age 57.9 years; 62.9% female). Internal carotid artery lesions were graded as 0%, 1-24%, >25% diameter narrowing and intima-media thickness (IMT) was measured. Plaque was present for any stenosis > 0%. CAC progression was evaluated with multivariable relative risk regression in cases with CAC = 0 at baseline and with multivariable linear regression for CAC > 0 adjusting for cardiovascular risk factors, body mass index, ethnicity, and common carotid IMT.
Results
CAC was positive at baseline in 2708/5445 (49.7%) participants and became positive in 458/2837 (16.1%) at mean interval of 2.4 years between repeat examinations. Plaque and ICA IMT were both strongly associated with presence of CAC. After statistical adjustment, presence of carotid artery plaque significantly predicted incident CAC with a relative risk(RR) of 1.37 (95% Confidence Intervals: 1.12, 1.67). Incident CAC was associated with ICA IMT with an RR of 1.13 (95% Confidence Intervals: 1.03, 1.25) for each mm increase. Progression of CAC was also significantly associated (p < 0.001) with plaque and ICA IMT.
Conclusions
In individuals free of cardiovascular disease, subjective and quantitative measures of carotid artery plaques by ultrasound imaging are associated with CAC incidence and progression.
doi:10.1016/j.echo.2013.02.009
PMCID: PMC4084492  PMID: 23522805
9.  Changes in Clinical and Microbiological Periodontal Profiles Relate to Progression of Carotid Intima‐Media Thickness: The Oral Infections and Vascular Disease Epidemiology Study 
Background
No prospective studies exist on the relationship between change in periodontal clinical and microbiological status and progression of carotid atherosclerosis.
Methods and Results
The Oral Infections and Vascular Disease Epidemiology Study examined 420 participants at baseline (68±8 years old) and follow‐up. Over a 3‐year median follow‐up time, clinical probing depth (PD) measurements were made at 75 766 periodontal sites, and 5008 subgingival samples were collected from dentate participants (average of 7 samples/subject per visit over 2 visits) and quantitatively assessed for 11 known periodontal bacterial species by DNA‐DNA checkerboard hybridization. Common carotid artery intima‐medial thickness (CCA‐IMT) was measured using high‐resolution ultrasound. In 2 separate analyses, change in periodontal status (follow‐up to baseline), defined as (1) longitudinal change in the extent of sites with a ≥3‐mm probing depth (Δ%PD≥3) and (2) longitudinal change in the relative predominance of bacteria causative of periodontal disease over other bacteria in the subgingival plaque (Δetiologic dominance), was regressed on longitudinal CCA‐IMT progression adjusting for age, sex, race/ethnicity, diabetes, smoking status, education, body mass index, systolic blood pressure, and low‐density lipoprotein cholesterol and high‐density lipoprotein cholesterol. Mean (SE) CCA‐IMT increased during follow‐up by 0.139±0.008 mm. Longitudinal IMT progression attenuated with improvement in clinical or microbial periodontal status. Mean CCA‐IMT progression varied inversely across quartiles of longitudinal improvement in clinical periodontal status (Δ%PD≥3) by 0.18 (0.02), 0.16 (0.01), 0.14 (0.01), and 0.07 (0.01) mm (P for trend<0.0001). Likewise, mean CCA‐IMT increased by 0.20 (0.02), 0.18 (0.02), 0.15 (0.02), and 0.12 (0.02) mm (P<0.0001) across quartiles of longitudinal improvement in periodontal microbial status (Δetiologic dominance).
Conclusion
Longitudinal improvement in clinical and microbial periodontal status is related to a decreased rate of carotid artery IMT progression at 3‐year average follow‐up.
doi:10.1161/JAHA.113.000254
PMCID: PMC3886779  PMID: 24166489
atherosclerosis; infection; inflammation; periodontal; progression
10.  Coronary Artery Calcium, Carotid Artery Wall Thickness and Cardiovascular Disease Outcomes in Adults 70 to 99 Years Old 
The American journal of cardiology  2008;101(2):186-192.
Few population studies have evaluated the associations of both coronary artery calcium (CAC) and carotid ultrasound with cardiovascular events, especially in adults > 70 years of age. At the Pittsburgh Field Center of the Cardiovascular Health Study, 559 men and women, mean age 80.2 (SD 4.1) years had CAC score assessed by electron beam computerized tomography scan and common and internal carotid intimal-medial wall thickness (CCA-IMT and ICA-IMT) by carotid ultrasound between 1998−2000 and were followed for total and incident cardiovascular disease events through June 2003. Crude rates and hazard ratios for total and incident events were examined with and without adjustment for cardiovascular risk factors. After 5 years, there were 127 cardiovascular disease events, 48 myocardial infarctions or cardiovascular disease deaths and 28 strokes or stroke deaths. Total and incident cardiovascular disease event rates were higher in each quartile of CAC and CCA-IMT, but not ICA-IMT. For total cardiovascular disease, the adjusted hazard ratio for the 4th vs. 1st quartile of CAC was 2.1 (95% CI = 1.2−3.9) and for CCA-IMT was 2.3 (95% CI = 1.3−4.1). The CCA-IMT was more strongly related to stroke risk than was CAC, though CAC was also an important predictor of stroke. No significant sex differences were found, though relative risks appeared to be stronger in women, especially for stroke. In conclusion, in these adults > 70 years of age, CAC and CCA-IMT had similar hazard ratios for total cardiovascular disease and coronary heart disease. The CCA-IMT was more strongly related to stroke than was CAC, but CAC was also a predictor of stroke.
doi:10.1016/j.amjcard.2007.07.075
PMCID: PMC2213559  PMID: 18178404
calcium; cardiovascular diseases; coronary disease; prognosis
11.  Associations of Carotid Artery Intima-Media Thickness (IMT) With Risk Factors and Prevalent Cardiovascular Disease 
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.
PMCID: PMC3186063  PMID: 21098848
atherosclerosis; carotid artery; disease prevalence; intima-media thickness; risk factors
12.  Effects of Obesity, Body Composition, and Adiponectin on Carotid Intima-Media Thickness in Healthy Women 
Context
Increased common carotid intima-media thickness (IMT) is predictive of coronary artery disease and stroke.
Objective
In this study, we investigated common carotid IMT by obesity category in a cohort of healthy women without previously known cardiovascular disease.
Design, Setting, Participants, and Main Outcome Measures
One hundred healthy women (aged 24-59 yr) from the general community enrolled in an observational study conducted at an academic medical center participated in the study. B-mode ultrasound imaging of the common carotid arteries was used to measure common carotid IMT in 99 subjects. Fat distribution was determined by computed tomography. Hormonal and inflammatory parameters related to cardiovascular disease and obesity were measured.
Results
IMT was higher in obese [body mass index (BMI) ≥ 30 kg/m2], compared with overweight women (BMI ≥ 25 and < 30 kg/m2) [0.69 mm, interquartile range (IQR) 0.60-0.75 mm] vs. 0.62 mm [IQR 0.56-0.68 mm), P = 0.044] and in comparison with lean women (BMI < 25 kg/m2) [0.69 mm (IQR 0.60-0.75 mm) vs. 0.59 mm (IQR 0.54-0.67 mm), P = 0.016]. In multivariate modeling, age (beta = 0.0050 mm change in IMT per year of age, P = 0.003), smoking (beta = 0.0044 mm change in IMT per pack-year, P = 0.046), and sc abdominal adiposity (beta = 0.00026 mm change in IMT per square centimeter, P = 0.010) were positively associated with IMT, whereas adiponectin (beta =–0.0042 mm change in IMT per milligram per liter, P = 0.045) was negatively associated with IMT. Visceral adiposity (beta = 0.00048 mm change in IMT per square centimeter, P = 0.092) was not significantly associated with IMT after adjusting for age, race, smoking, sc abdominal adiposity, and adiponectin.
Conclusions
Obesity is associated with increased common carotid IMT in young and middle-aged women. Adiponectin and sc abdominal adiposity are associated with carotid IMT in this population.
doi:10.1210/jc.2005-2775
PMCID: PMC3210448  PMID: 16522690
13.  Association Between Carotid Intima-Media Thickness and Pericardial Fat in the Multi-Ethnic Study of Atherosclerosis (MESA) 
Introduction
Carotid intima-media thickness (IMT) is a sub-clinical marker of atherosclerosis and a strong predictor of stroke. Pericardial fat (PF), the fat depot around the heart, has been associated with several atherosclerosis risk factors. We sought to examine the association between carotid IMT and PF, and to examine whether such an association is independent from common atherosclerosis risk factors including measures of overall adiposity.
Methods
Unadjusted and multivariable adjusted linear regression analysis was used to examine associations between common (CCA-IMT) and internal (ICA-IMT) carotid IMT with PF in a random sample of 996 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) who underwent carotid ultrasound and chest CT at baseline examination.
Results
A significant positive correlation was observed between PF and CCA-IMT (r =0.27, P<0.0001) and ICA-IMT (r =0.17, P<0.0001). In an unadjusted sex-specific linear regression analysis, there was a significant association between PF (1-SD difference) and CCA-IMT (mm) in both women (β coefficient (95% CI): 0.06 (0.04, 0.08), P<0.0001) and men (0.03 (0.01, 0.05), P<0.0002), an association that persisted after further adjusting for age and ethnicity (0.02 (+0.00, 0.04), P=0.0120 for women, and 0.02 (+0.00, 0.03), P=0.0208 for men). However, after additional adjustment for atherosclerosis risk factors and either BMI or waist circumference, these relations were no longer significant in either sex. In similar analyses, PF was significantly associated with ICA-IMT in both men (0.11 (0.06, 0.15), P<0.0001) and women (0.08 (0.02, 0.13), P=041). These relations were no longer significant in women in multivariable adjusted models, but persisted in men in all models except after adjusting for age, ethnicity and waist circumference.
Conclusions
In the general population PF is associated with carotid IMT, an association that possibly not independent from markers of overall adiposity or common atherosclerosis risk factors.
doi:10.1016/j.jstrokecerebrovasdis.2009.03.008
PMCID: PMC2817960  PMID: 20123228
14.  Bone mineral density and atherosclerosis: The Multi-Ethnic Study of Atherosclerosis, Abdominal Aortic Calcium Study 
Atherosclerosis  2009;209(1):283-289.
Context
Molecular and cell biology studies have demonstrated an association between bone and arterial wall disease, but the significance of a population-level association is less clear and potentially confounded by inability to account for shared risk factors.
Objective
To test population-level associations between atherosclerosis types and bone integrity.
Main Outcome Measures
Volumetric trabecular lumbar bone mineral density (vBMD), ankle-brachial index (ABI), intima-media thickness of the common carotid (CCA-IMT) and internal carotid (ICA-IMT) arteries, and carotid plaque echogenicity.
Design, Setting and Participants
A random subset of participants from the Multi-Ethnic Study of Atherosclerosis (MESA) assessed between 2002 and 2005.
Results
904 post-menopausal female (62.4 years; 62% non-white; 12% ABI<1; 17% CCA-IMT>1mm; 33% ICA-IMT>1mm) and 929 male (61.4 years; 58% non-white; 6% ABI<1; 25% CCA-IMT>1mm; 40% ICA-IMT>1mm) were included. In serial, sex-specific regression models adjusting for age, ethnicity, body mass index, dyslipidemia, hypertension, smoking, alcohol consumption, diabetes, homocysteine, interleukin-6, sex hormones, and renal function, lower vBMD was associated with lower ABI in men (p for trend <0.01) and greater ICA-IMT in men (p for trend <0.02). CCA-IMT was not associated with vBMD in men or women. Carotid plaque echogenicity was independently associated with lower vBMD in both men (trend p=0.01) and women (trend p<0.04). In all models, adjustment did not materially affect results.
Conclusions
Lower vBMD is independently associated with structural and functional measures of atherosclerosis in men and with more advanced and calcified carotid atherosclerotic plaques in both sexes.
doi:10.1016/j.atherosclerosis.2009.09.011
PMCID: PMC4254856  PMID: 19819456
15.  Longitudinal Predictors of Progression of Carotid Atherosclerosis in Rheumatoid Arthritis 
Arthritis and rheumatism  2011;63(11):3216-3225.
Objective
To explore predictors of change in measures of carotid atherosclerosis among rheumatoid arthritis (RA) patients without known cardiovascular disease (CVD) at baseline
Methods
RA patients underwent carotid ultrasonography at two timepoints, separated by an average of 3.2 ± 0.3 years. The associations of baseline and average patient characteristics with the average yearly change in mean maximal intima-medial thickness (IMT) of the common (CCA) and internal carotid arteries (ICA), and with incident or progressive plaque in the ICA/carotid bulb, were explored.
Results
Among the 158 RA patients, maxCCA-IMT increased in 82% (median=16 μm/year; p<0.001) and maxICA-IMT increased in 70% (median=25 μm/year; p<0.001). Incident plaque was observed in 14% without baseline plaque [incidence rate=4.2/100 person-years (95% CI 1.61–6.82)]. Plaque progression was observed in 5% with baseline plaque. Among RA predictors, the adjusted average yearly change in maxCCA-IMT was significantly greater in patients with earlier RA vs. longer disease. Those prescribed TNF inhibitors at baseline had a 37% lower adjusted rate of maxCCA-IMT progression vs. non-users (14 vs. 22 μm/year; p=0.026). For maxICA-IMT, cumulative prednisone exposure was associated with progression [1.2 μm/year per gram (95% CI 0.1–2.4)] after adjustment, and was lower in patients prescribed statins concomitant with prednisone. Higher swollen joint count and higher average CRP were both associated with incident or progressive plaque, primarily in patients with elevated baseline CVD risk based on the Framingham score.
Conclusions
These prospective data provide evidence for inflammation as a contributor to subclinical atherosclerosis progression in RA, potentially modified favorably by TNF inhibitors and detrimentally by glucocorticoids.
doi:10.1002/art.30542
PMCID: PMC3205252  PMID: 21965129
Atherosclerosis; Inflammation; prediction; carotid ultrasound
16.  Associations of cardiovascular risk factors, carotid intima-media thickness and left ventricular mass with inter-adventitial diameters of the common carotid artery: the Multi-Ethnic Study of Atherosclerosis (MESA) 
Atherosclerosis  2011;218(2):344-349.
Background
Common carotid artery inter-adventitial diameter (IAD) and intima-media thickness (IMT) are measurable by ultrasound. IAD may be associated with left ventricular mass (LV mass) while IMT is a marker of subclinical atherosclerosis. It is not clear if IAD is associated with LV mass after accounting for IMT and traditional cardiovascular risk factors.
Methods
IAD and IMT were measured on participants of the Multi-Ethnic Study of Atherosclerosis (MESA) IMT progression study. A total of 5641 of the originally enrolled 6814 MESA participants were studied. LV mass was measured by magnetic resonance imaging. Multivariable linear regression was used with IAD as the outcome and adjustment for risk factors, as well as IMT and LV mass.
Results
Traditional cardiovascular risk factors, height, weight and ethnicity were significantly associated with IAD. After adjustment for risk factors, a one mm difference in IMT was associated with a 1.802 mm (95% CI: 1.553, 2.051) higher mean IAD. A one gm difference in LV mass was associated with a 0.006 mm (95% CI: 0.005, 0.007) higher mean IAD. LV mass was independently associated with IAD after adjusting for cardiovascular risk factors and IMT. These associations were slightly different for men and women.
Conclusions
Inter-adventitial diameters are associated with left ventricular mass after adjusting for cardiovascular risk factors and IMT. IAD might serve as a surrogate for left ventricular mass and have predictive value for cardiovascular outcomes.
doi:10.1016/j.atherosclerosis.2011.05.033
PMCID: PMC3186064  PMID: 21726862
carotid arteries; ultrasonics; hypertrophy; magnetic resonance imaging; remodeling; risk factors; left ventricle
17.  Bilateral common carotid artery ultrasound for prediction of incident strokes using intima-media thickness and external diameter: an observational study 
Background
External common carotid artery (CCA) diameter and intima-media thickness (IMT) are independently associated with incident stroke and other cardiovascular events. Arterial geometry such as large IMT and large diameter may reflect vulnerable plaques and so impact stroke risk. Finally, arterial changes that exist bilaterally may increase stroke risk.
Method
We studied middle-aged men and women (n=7276) from a prospective observational study who had right (R) and left (L) CCA IMT and external diameters measured via B-mode ultrasound (1987–89) in order to categorize CCA geometry. Using side- and gender-specific IMT and diameter medians, we categorized each measurement as large (≥ median) vs. not large (< median) and defined four geometries: both IMT and diameter were large, only one parameter was large, or neither was large (reference group). Participants were followed for first time stroke through December 31, 1999. We used proportional hazards models to assess associations between right and left CCA geometries with new stroke. We also calculated positive and negative likelihood ratios (+LR and -LR) for CCA bilateral phenotypes as a measure of diagnostic accuracy.
Results
Presence of both large CCA IMT and large diameter on one side was associated with strong stroke risk even after risk factor adjustment (men: RCCA hazard ratio [HR]=3.7 95% confidence interval [CI]=1.9-7.4; LCCA HR=2.4 95% CI=1.4-4.4; women: RCCA HR=4.0 95% CI=1.5-10.5; LCCA HR=5.7 95% CI=1.7-19.0). Presence of both large IMT and large diameter bilaterally was the strongest predictor of stroke identifying 64% of women and 44% of men who developed strokes. This phenotype showed potential for predicting stroke among individuals (women: +LR=3.1, 95% CI=2.6-3.8; men: +LR=2.3, 95% CI=1.8-2.8).
Conclusion
Bilateral carotid artery geometries may be useful for stroke risk prediction.
doi:10.1186/1476-7120-11-22
PMCID: PMC3686606  PMID: 23768019
Stroke; Atherosclerosis; Carotid arteries; Ultrasound; Intima-media thickness; Arterial diameter; Arterial geometry; Bilateral; Prospective study
18.  Snoring and Insomnia are Not Associated with Subclinical Atherosclerosis in the Northern Manhattan Study (NOMAS) 
Background and Aims
Sleep disordered breathing (SDB) is a risk factor for stroke, but its association with subclinical atherosclerosis remains controversial. Snoring and insomnia are frequently co-morbid with SDB and may contribute to stroke. Data on the relationship between snoring and insomnia with atherosclerotic disease is sparse. We investigated the relationship between insomnia, snoring and carotid intima-media thickness (IMT), a marker of subclinical atherosclerosis, in the Northern Manhattan Study (NOMAS).
Methods
A group of 1,605 participants (mean age 65 ± 8 years; 40% men; 61% Hispanic, 19% black, 20% white) who had carotid IMT measurements performed was assessed for self-reported sleep habits. Habitual snoring was defined as self-reported snoring > 4 times per week. Presence of insomnia was based on three items extracted from the Hamilton Rating Scale for Depression. Carotid IMT was expressed as a mean composite measure of IMT in the carotid bifurcation, common and internal carotid artery. Multivariate linear regression models were used to identify associations between snoring, insomnia and carotid IMT.
Results
Habitual snoring was present in 29% of the subjects and insomnia in 26%. There was a higher prevalence of self reported snoring (84%) and insomnia (66%) among Hispanics than non-Hispanics. The mean total carotid IMT was 0.95 ± 0.09 mm; among those with self reported snoring was 0.94 ± 0.09 mm; and among those with insomnia was 0.95 ± 0.08 mm. After controlling for age, sex, race-ethnicity, BMI and cardiovascular risk factors, snoring (p= 0.986) and insomnia (p= 0.829) were not significantly associated with increased carotid IMT.
Conclusion
Snoring and insomnia were not significantly associated with subclinical atherosclerosis in this population based community cohort.
doi:10.1111/j.1747-4949.2010.00438.x
PMCID: PMC2907549  PMID: 20636708
sleep; snoring; insomnia; African American; Hispanic; Intima-Media Thickness; Risk factors; Sonography; Ultrasound
19.  Carotid Intima‐Media Thickness is Associated With Incident Heart Failure Among Middle‐Aged Whites and Blacks: The Atherosclerosis Risk in Communities Study 
Background
Increased carotid intima‐media thickness (IMT) is associated with subclinical left ventricular myocardial dysfunction, suggesting a possible role of carotid IMT in heart failure (HF) risk determination.
Methods and Results
Mean far wall carotid IMT, measured by B‐mode ultrasound, was available for 13 590 Atherosclerosis Risk in Communities study participants aged 45 to 64 years and free of HF at baseline. HF was defined using ICD‐9 428 and ICD‐10 I‐50 codes from hospitalization records and death certificates. The association between carotid IMT and incident HF was assessed using Cox proportional hazards analysis with models adjusted for demographic variables, major CVD risk factors, and interim CHD. There were 2008 incident HF cases over a median follow‐up of 20.6 years (8.1 cases per 1000 person‐years). Mean IMT was higher in those with HF than in those without (0.81 mm±0.23 versus 0.71 mm±0.17, P<0.001). Unadjusted rate of HF for the fourth compared with the first quartile of IMT was 15.4 versus 3.9 per 1000 person‐years; P<0.001. In multivariable analysis, after adjustment, each standard deviation increase in IMT was associated with incident HF (HR 1.20 [95% CI: 1.16 to 1.25]). After adjustment, the top quartile of IMT was associated with HF (HR 1.60 [95% CI: 1.37 to 1.87]). Results were similar across race and gender groups.
Conclusions
Increasing carotid IMT is associated with incident HF in middle‐aged whites and blacks, beyond risks explained by major CVD risk factors and CHD. This suggests that carotid IMT may be associated with HF through mechanisms different from myocardial ischemia or infarction.
doi:10.1161/JAHA.114.000797
PMCID: PMC4309069  PMID: 24815496
carotid intima‐media thickness; heart failure; subclinical atherosclerosis
20.  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 
Background
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.
Methods
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.
Results
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.
Conclusion
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.
doi:10.1186/1476-7120-6-10
PMCID: PMC2277382  PMID: 18321381
21.  Retinal Microvascular Signs and Risk of Stroke: The Multi-Ethnic Study of Atherosclerosis (MESA) 
Background and Purpose
Small vessel disease contributes to the pathophysiology of stroke, and retinal microvascular signs have been linked to risk of stroke. We examined the relationship of retinal signs with incident stroke in a multi-ethnic cohort.
Methods
The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective cohort study that enrolled participants without clinical cardiovascular diseases from six United States communities between 2000–02. Of the participants, 4,849 (71.2%) had fundus photography performed in 2002–04. Retinopathy and retinal vessel caliber were assessed from retinal images. Stroke risk factors including high-sensitivity C-reactive protein (hsCRP), carotid artery intima-media thickness (IMT) and coronary artery calcium (CAC) were measured using standardized protocols. Incident stroke was confirmed from medical record review and death certificates.
Results
After 6 years of follow-up, there were 62 incident strokes. Narrower retinal arteriolar caliber was associated with increased risk of stroke after adjusting for conventional cardiovascular risk factors (adjusted incidence rate ratio [IRR] 2.83, 95% confidence interval [CI] 1.34–5.95, p=0.006; adjusted hazard ratio [HR] 3.01, 95% CI 1.29–6.99, p=0.011). Retinopathy in persons without diabetes was associated with increased risk of stroke (adjusted IRR 2.96, 95% CI 1.50–5.84, p=0.002; adjusted HR 3.07, 95%CI 1.17–8.09, p=0.023). These associations remained significant after adjusting for hsCRP, carotid IMT or CAC.
Conclusions
Narrower retinal arteriolar caliber and retinopathy in non-diabetic persons were associated with increased risk of stroke in this relatively healthy multi-ethnic cohort independent of traditional risk factors and measures of atherosclerosis. The association between narrower retinal arteriolar caliber and stroke warrants further investigation.
doi:10.1161/STROKEAHA.112.673335
PMCID: PMC3508325  PMID: 23111439
Stroke; Retinal microvascular signs; Retinopathy; Retinal vessel caliber
22.  Relationship Between Brachial Flow - Mediated Dilation and Carotid Intima- Media Thickness in an Elderly Cohort: The Cardiovascular Health Study 
Atherosclerosis  2007;197(2):840-845.
Objective
The aim of this study was to determine the relationship between brachial flow-mediated dilation (FMD) and carotid intima-media thickness (IMT) in a large multi-ethnic elderly cohort.
Background
Brachial flow-mediated dilation (FMD) is a physiologic measure and Carotid IMT is an anatomic structural measure of subclinical atherosclerosis. Both brachial FMD and carotid IMT have been associated with cardiovascular risk factors and cardiovascular events. The relationship between brachial FMD and carotid IMT is less clear especially in older adults.
Methods
Brachial FMD, carotid IMT and traditional cardiovascular risk factors were measured in 2338 adults, age 72–98 years who were participants in the Cardiovascular Health Study. The relationship between FMD and IMT was assessed both unadjusted and also after adjusting for age, gender, race/ethnicity. BMI, HDL, LDL, systolic and diastolic blood pressure, serum creatinine, current smoking, diabetes mellitus, hormone therapy and prior CVD.
Results
Both brachial FMD and carotid IMT correlated significantly with age, HDL levels, waist/hip ratio, serum cholesterol and number of CV risk factors. Brachial FMD was not associated with CCA IMT in this elderly cohort (Pearson partial correlation coefficient= −0.0252, p=0.222). In the adjusted linear regression model with CCA IMT as the dependent variable, brachial FMD was also not associated with CCA IMT (beta coefficient= −0.006, p=0.470)
Conclusion
Brachial FMD and CCA IMT are not related in population-based older adults. Brachial FMD and CCA IMT may be distinct and independent stages in the complex atherosclerotic process.
doi:10.1016/j.atherosclerosis.2007.07.032
PMCID: PMC4115586  PMID: 17804000
Brachial flow-mediated dilation; carotid intima-media thickness; endothelial function; atherosclerosis; elderly
23.  Segment-specific association between plasma homocysteine and carotid artery intima-media thickness in the Framingham Heart Study 
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.
doi:10.1016/j.jstrokecerebrovasdis.2009.10.012
PMCID: PMC3011043  PMID: 20580253
carotid artery; intima-media thickness; homocysteine; atherosclerosis; Framingham Offspring Study
24.  Association between circulating leukocyte subtype counts and carotid intima-media thickness in Japanese subjects with type 2 diabetes 
Background
An increased leukocyte count is an independent risk factor for cardiovascular events, but the association between leukocyte subtype counts and carotid atherosclerosis in patients with diabetes has not been determined. We therefore investigated the correlation between leukocyte subtype counts and intima-media thickness of the common carotid artery (CCA-IMT) in subjects with type 2 diabetes.
Methods
This cross-sectional study involved 484 in-patients with type 2 diabetes (282 males and 202 females), who were hospitalized for glycemic control and underwent carotid ultrasonography at Kumamoto University Hospital between 2005 and 2011. Mean and maximum CCA-IMT was measured by high-resolution B-mode ultrasonography.
Results
Univariate analyses revealed that mean CCA-IMT was positively correlated with age, systolic blood pressure, brachial-ankle pulse wave velocity (PWV), urinary albumin excretion and duration of diabetes, but was negatively correlated with diastolic blood pressure and fasting plasma glucose. Maximum CCA-IMT was positively and negatively correlated with the same factors as mean CCA-IMT except for fasting plasma glucose. Mean CCA-IMT was positively correlated with total leukocyte (r = 0.124, p = 0.007), monocyte (r = 0.373, p < 0.001), neutrophil (r = 0.139, p = 0.002) and eosinophil (r = 0.107, p = 0.019) counts. Maximum CCA-IMT was positively correlated with total leukocyte (r = 0.154, p < 0.001), monocyte (r = 0.398, p < 0.001), neutrophil (r = 0.152, p < 0.001) and basophil counts (r = 0.102, p = 0.027). Multiple regression analyses showed that monocyte count, age and PWV were significant and independent factors associated with mean CCA-IMT (adjusted R2 = 0.239, p < 0.001), and that monocyte count, age and urinary albumin excretion were significant and independent factors associated with maximum CCA-IMT (adjusted R2 = 0.277, p < 0.001).
Conclusions
Monocyte counts were positively correlated with both mean CCA-IMT and maximum CCA-IMT in patients with type 2 diabetes. Monocyte count may be a useful predictor of macrovascular complications in patients with type 2 diabetes.
Trial registration
Trial registry no: UMIN000003526.
doi:10.1186/1475-2840-12-177
PMCID: PMC3878795  PMID: 24373412
Leukocyte subtype counts; Carotid intima-media thickness; Diabetic macrovascular complication; Type 2 diabetes
25.  Cystatin C and Carotid Intima-Media Thickness in Asymptomatic Adults: The Multi-Ethnic Study of Atherosclerosis (MESA) 
Background
Persons with early kidney disease have an increased risk of cardiovascular events and mortality, but the importance of accelerated atherosclerosis in promoting these outcomes is unclear. We therefore explored whether serum cystatin C level is associated with carotid intima-media thickness (IMT) in ambulatory adults without clinical heart disease.
Study Design
Cross-sectional study.
Setting & Participants
We evaluated 6,557 ethnically diverse persons free of clinical cardiovascular disease aged 45 to 84 years at the baseline visit of the Multi-Ethnic Study of Atherosclerosis.
Predictors
Kidney function was estimated by using 2 methods: serum cystatin C level and estimated glomerular filtration rate, based on creatinine and cystatin C levels.
Outcomes & Measurements
Study outcomes were internal and common carotid IMT, measured by using high-resolution B-mode ultrasound. Multivariate linear and logistic regressions were used to evaluate the independent association of kidney function with carotid IMT.
Results
In unadjusted linear analysis, each SD (0.23 mg/L) greater cystatin C level was associated with 0.091-mm greater internal carotid IMT (P < 0.001), but this association was diminished by 70% after adjustment for age, sex, and race/ethnicity (0.027 mm; P < 0.001) and was no longer significant after adjustment for cardiovascular risk factors (0.005 mm; P = 0.5). Similarly, the strong unadjusted associations of cystatin C level with common carotid IMT disappeared after adjustment. Chronic kidney disease, defined by using either creatinine level or cystatin C–based estimated glomerular filtration rate less than 60 mL/min/1.73 m2, had no independent association with internal and common carotid IMT.
Limitations
There were few participants with severe kidney disease.
Conclusions
Cystatin C level had no independent association with carotid IMT in a population free of clinical heart disease. This observation suggests that accelerated atherosclerosis is unlikely to be the primary mechanism explaining the independent association of cystatin C level with cardiovascular risk.
doi:10.1053/j.ajkd.2008.06.025
PMCID: PMC3046734  PMID: 18823684
Cystatin C; intima-media thickness (IMT); atherosclerosis; cardiovascular diseases; kidney

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