PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-8 (8)
 

Clipboard (0)
None
Journals
Year of Publication
Document Types
1.  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
2.  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
3.  Carotid-Wall Intima–Media Thickness and Cardiovascular Events 
The New England journal of medicine  2011;365(3):213-221.
BACKGROUND
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.
METHODS
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.
RESULTS
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).
CONCLUSIONS
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.)
doi:10.1056/NEJMoa1012592
PMCID: PMC3153949  PMID: 21774709
4.  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
5.  Association of the Endogenous Nitric Oxide Synthase Inhibitor ADMA with Carotid Artery Intimal Media Thickness in the Framingham Heart Study Offspring Cohort 
Background and Purpose
Higher plasma concentrations of the endogenous nitric oxides synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) are associated with increased risk of cardio- and cerebrovascular events and death, presumably by promoting endothelial dysfunction and subclinical atherosclerosis. We hypothesized that plasma ADMA concentrations are positively related to common carotid artery intimal media thickness (CCA-IMT) and to internal carotid (ICA)/bulb-IMT.
Methods
We investigated the cross-sectional relations of plasma ADMA with CCA-IMT and ICA/bulb-IMT in 2958 Framingham Heart Study participants (mean age 58 years, 55% women).
Results
In unadjusted analyses, ADMA was positively related to both CCA-IMT (β per SD increment 0.012, p<0.001) and ICA/bulb IMT (β per SD increment 0.059, p<0.001). In multivariable analyses (adjusting for age, sex, systolic blood pressure, antihypertensive treatment, smoking status, diabetes, body mass index (BMI), Total to HDL cholesterol ratio, log C-reactive protein, and serum creatinine), plasma ADMA was not associated with CCA-IMT (p=0.991), but remained significantly and positively related to ICA/bulb IMT (β per SD increment 0.0246, p=0.002).
Conclusions
In our large community-based sample, we observed that higher plasma ADMA concentrations were associated with greater ICA/bulb-IMT but not with CCA-IMT. These data are consistent with the notion that ADMA promotes subclinical atherosclerosis in a site-specific manner, with a greater proatherogenic influence at known vulnerable sites in the arterial tree.
doi:10.1161/STROKEAHA.109.552539
PMCID: PMC2749947  PMID: 19498184
Carotid Intimal Medial Thickness; Endothelium; Epidemiology; Risk Factors; Nitric Oxide
6.  Carotid Artery Atherosclerosis, MRI Indices of Brain Ischemia and Aging and Cognitive Impairment: The Framingham Study 
Background and Purpose
Carotid atherosclerosis has been associated with increased risk of stroke, and poorer cognitive performance in older adults. The relation of carotid atherosclerosis to cognitive impairment and MRI indices of ischemia and aging in midlife is less clear.
Methods
We studied 1,975 Framingham Offspring Study participants free of stroke and dementia with available carotid ultrasound, brain MRI and neuropsychological testing. We related common and internal carotid artery intima-media thickness (ICA-IMT and CCA-IMT respectively) and internal carotid stenosis (CAS) to large white matter hyperintensity (>1-SD above age-specific mean; LWMH), total brain volume (TCBV), hippocampal volume, silent cerebral infarcts (SCI) and neuropsychological measures of verbal memory, executive function and non-verbal memory measures.
Results
We observed that ICA-IMT, but not CCA-IMT, was associated with higher prevalence of SCI (OR 1.21, 95% CI 1.03–1.43, p<0.05), LWMH (OR 1.19, 95% CI 1.03–1.38, p<0.05), lower TCBV (−0.05 per SD, p<0.05) and poorer performance in verbal memory (−0.06 per SD; p<0.05) and non-verbal memory measures (−0.08 per SD; p<0.01), but not with hippocampal volume. CAS ≥25% was associated with a higher prevalence of LWMH (adjusted OR 1.77, 95% CI 1.25–2.53) and lower TCBV (−0.11 per SD, p=0.042) but not with SCI or hippocampal volume. CAS ≥50% was associated with higher prevalence of SCI (OR 2.53, 95% CI 1.17 – 5.44), LWMH (OR 2.35, 95% CI 1.08–5.13) and poorer performance on executive function (−0.39 per SD; p<0.05) but not with TCBV or hippocampal volume.
Conclusions
Carotid atherosclerosis markers were associated with MRI indices of brain ischemia and aging and with cognitive impairment in a community-based sample of middle-aged adults. Our data suggest that ICA-IMT may be a better marker for cognitive impairment than CCA-IMT.
doi:10.1161/STROKEAHA.108.535245
PMCID: PMC2705324  PMID: 19265054
Carotid atherosclerosis; brain MRI; cognitive performance
7.  Association of Carotid Artery Atherosclerosis with Circulating Biomarkers of Extracellular Matrix Remodeling: The Framingham Offspring Study 
Objective
To relate circulating biomarkers of extracellular matrix (ECM) turnover to site-specific measures of carotid artery atherosclerosis on duplex ultrasound.
Background
Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) regulate ECM remodeling, a key feature of atherosclerosis, and their circulating concentrations can be assayed. MMP-9, TIMP-1 and protocollagen-III n-terminal propeptide (PIIINP) may relate differentially to the severity of atherosclerosis at different carotid artery sites. However, data examining this premise are sparse.
Design/Methods
We related circulating MMP-9, TIMP-1 and/or PIIINP concentrations to carotid atherosclerosis on duplex ultrasound in1006 Framingham Offspring (mean age 58 years, 56% women) who attended a routine examination from 1995–1998. We used multivariable regression to relate MMP-9 (detectable versus undetectable), and TIMP-1 and PIIINP (age- and sex-specific quartiles) to internal carotid artery stenosis (>25%), and log-transformed common and internal carotid intima-media thickness (CC-IMT, IC-IMT, respectively).
Results
Detectable MMP-9 was associated with carotid stenosis (OR 1.71, p=0.032) but not with IMT. Higher TIMP-1 was associated with carotid stenosis (OR for Q4 versus Q1-3, 1.63, p=0.022) and a higher IC-IMT (β 0.057 ±0.025, Q4 versus Q1-3, p=0.023). Higher PIIINP (Q4 versus Q1-3) showed a borderline association with carotid stenosis (OR 1.45 for Q4 versus Q1-3, p=0.095) but not with IMT. TIMP-1 was not associated with CC-IMT.
Conclusions
In our community-based sample of middle-aged to older adults, higher circulating biomarkers of matrix remodeling were associated with a greater prevalence of carotid stenosis, and subclinical atherosclerosis in the IC artery. Our findings are consistent with regional differences in matrix remodeling in the carotid artery.
doi:10.1016/j.jstrokecerebrovasdis.2008.06.002
PMCID: PMC2613480  PMID: 18984437
Carotid artery; atherosclerosis; matrix proteins; intima media thickness; stenosis
8.  Prevalence and Correlates of Silent Cerebral Infarcts in the Framingham Offspring Study 
Background and Purpose
Prior estimates of the prevalence of silent cerebral infarction (SCI) on magnetic resonance imaging (MRI) in community-based samples have varied between 5.8 and 17.7% depending on age, ethnicity, presence of co-morbidities and imaging techniques. We document the prevalence and risk factors associated with SCI at midlife in the community-based Framingham sample.
Methods
2040 Framingham Offspring (53% F; mean age 62±9 yrs) who attended the 6th examination (1996–98), underwent volumetric brain MRI (1999–2005) and were free of clinical stroke at MRI, constituted our study sample. We examined the age- and sex-specific prevalence and the clinical correlates of SCI using multivariable logistic regression models.
Results
At least one SCI was present in 10.7% of participants. 84% had a single lesion. SCI were largely located in the basal ganglia (52%), other subcortical (35%) and cortical areas (11%). Prevalent SCI was associated with the Framingham Stroke Risk Profile score (OR: 1.27; 95% CI: 1.10 – 1.46); Stage I hypertension by JNC-VII criteria (OR:1.56; CI:1.15 – 2.11)), an elevated plasma homocysteine in the highest quartile (OR: 2.23; CI: 1.42 – 3.51), atrial fibrillation (OR: 2.16; CI: 1.07 – 4.40), carotid stenosis >25% (OR: 1.62; 1.13 – 2.34)) and increased carotid intimal-medial thickness above the lowest quintile (OR: 1.65; CI: 1.22 – 2.24).
Conclusion
The prevalence and distribution of SCI in the Framingham Offspring.is comparable to prior estimates. Risk factors previously associated with clinical stroke were also found to be associated with midlife SCI. Our results support current guidelines emphasizing early detection and treatment of stroke risk factors.
doi:10.1161/STROKEAHA.108.516575
PMCID: PMC2712254  PMID: 18583555
cerebral infarction; magnetic resonance imaging; risk factors; prevalence; hypertension

Results 1-8 (8)