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Activated TLR signaling in atherosclerosis among women with lower Framingham risk score: the multi-ethnic study of atherosclerosis.

ABSTRACT: Atherosclerosis is the leading cause of cardiovascular disease (CVD). Traditional risk factors can be used to identify individuals at high risk for developing CVD and are generally associated with the extent of atherosclerosis; however, substantial numbers of individuals at low or intermediate risk still develop atherosclerosis.A case-control study was performed using microarray gene expression profiling of peripheral blood from 119 healthy women in the Multi-Ethnic Study of Atherosclerosis cohort aged 50 or above. All participants had low (<10%) to intermediate (10% to 20%) predicted Framingham risk; cases (N?=?48) had coronary artery calcium (CAC) score >100 and carotid intima-media thickness (IMT) >1.0 mm, whereas controls (N?=?71) had CAC<10 and IMT <0.65 mm. We identified two major expression profiles significantly associated with significant atherosclerosis (odds ratio 4.85; P<0.001); among those with Framingham risk score <10%, the odds ratio was 5.30 (P<0.001). Ontology analysis of the gene signature reveals activation of a major innate immune pathway, toll-like receptors and IL-1R signaling, in individuals with significant atherosclerosis.Gene expression profiles of peripheral blood may be a useful tool to identify individuals with significant burden of atherosclerosis, even among those with low predicted risk by clinical factors. Furthermore, our data suggest an intimate connection between atherosclerosis and the innate immune system and inflammation via TLR signaling in lower risk individuals.

SUBMITTER: Huang CC

PROVIDER: S-EPMC3116882 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Activated TLR signaling in atherosclerosis among women with lower Framingham risk score: the multi-ethnic study of atherosclerosis.

Huang Chiang-Ching CC Liu Kiang K Pope Richard M RM Du Pan P Lin Simon S Rajamannan Nalini M NM Huang Qi-Quan QQ Jafari Nadereh N Burke Gregory L GL Post Wendy W Watson Karol E KE Johnson Craig C Daviglus Martha L ML Lloyd-Jones Donald M DM

PloS one 20110616 6

<h4>Background</h4>Atherosclerosis is the leading cause of cardiovascular disease (CVD). Traditional risk factors can be used to identify individuals at high risk for developing CVD and are generally associated with the extent of atherosclerosis; however, substantial numbers of individuals at low or intermediate risk still develop atherosclerosis.<h4>Results</h4>A case-control study was performed using microarray gene expression profiling of peripheral blood from 119 healthy women in the Multi-E ...[more]

PMID: 21698167

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Project description:BackgroundData are limited on the relation between dietary patterns and left ventricular (LV) structure and function.ObjectiveWe examined cross-sectional associations of a diet-score assessment of a Mediterranean dietary pattern with LV mass, volume, mass-to-volume ratio, stroke volume, and ejection fraction.DesignWe measured LV variables with the use of cardiac MRI in 4497 participants in the Multi-Ethnic Study of Atherosclerosis study who were aged 45-84 y and without clinical cardiovascular disease. We calculated a Mediterranean diet score from intakes of fruit, vegetables, nuts, legumes, whole grains, fish, red meat, the monounsaturated fat:saturated fat ratio, and alcohol that were self-reported with the use of a food-frequency questionnaire. We used linear regression with adjustment for body size, physical activity, and cardiovascular disease risk factors to model associations and assess the shape of these associations (linear or quadratic).ResultsThe Mediterranean diet score had a slight U-shaped association with LV mass (adjusted means: 146, 145, 146, and 147 g across quartiles of diet score, respectively; P-quadratic trend = 0.04). The score was linearly associated with LV volume, stroke volume, and ejection fraction: for each +1-U difference in score, LV volume was 0.4 mL higher (95% CI: 0.0, 0.8 mL higher), the stroke volume was 0.5 mL higher (95% CI: 0.2, 0.8 mL higher), and the ejection fraction was 0.2 percentage points higher (95% CI: 0.1, 0.3 percentage points higher). The score was not associated with the mass-to-volume ratio.ConclusionsA higher Mediterranean diet score is cross-sectionally associated with a higher LV mass, which is balanced by a higher LV volume as well as a higher ejection fraction and stroke volume. Participants in this healthy, multiethnic sample whose dietary patterns most closely conformed to a Mediterranean-type pattern had a modestly better LV structure and function than did participants with less-Mediterranean-like dietary patterns. This trial was registered at clinicaltrials.gov as NCT00005487.

Project description:PurposeTo develop a new calcium score for use with unenhanced cardiac computed tomography (CT) that can be used to define the percentage of coronary arteries affected by calcium and to correlate this score with risk factors and cardiovascular events.Materials and methodsInstitutional review boards at all participating centers approved this HIPAA-compliant study, and all participants gave written informed consent. Calcium coverage score (CCS), which represents the percentage of coronary arteries affected by calcific plaque, was calculated for 3252 participants in the Multi-Ethnic Study of Atherosclerosis in whom calcific plaque was detected with CT. Quasi-Poisson models were used to estimate associations (assessed by using t tests with robust standard errors) between CCS and risk factors. Associations between the CCS, Agatston, and calcium mass scores (hereafter, mass scores) and outcomes were estimated and assessed by using Cox proportional hazards models with Wald tests. The predictive ability of these models was assessed by using area under the receiver operating characteristic curves and bootstrap t tests.ResultsAfter adjustments were made for age, race, ethnicity, and sex in the quasi-Poisson model, CCS was associated with hypertension, dyslipidemia, and diabetes (P < .001 for all diseases). After adjustments for age and sex, a twofold increase in CCS was associated with a 52% (95% confidence interval: 34%, 72%) increase in risk for any coronary heart disease (CHD) event. When Agatston or mass scores were included with CCS in a Cox model for prediction of CHD events, neither Agatston score nor mass score was a significant predictor, whereas CCS remained significantly associated with CHD events. Although receiver operating characteristic curves suggested that there was a difference between CCS score and Agatston and mass scores in prediction of a cardiac event, no differences in prediction of hard cardiac events (myocardial infarction, death) were found.ConclusionBoth spatial distribution and amount of calcified plaque contribute to risk for CHD.

Project description:The aim of this study was to investigate whether inclusion of simple measures of calcified plaque distribution might improve the ability of the traditional Agatston coronary artery calcium (CAC) score to predict cardiovascular events.Agatston CAC scoring does not include information on the location and distributional pattern of detectable calcified plaque.We studied 3,262 (50%) individuals with baseline CAC >0 from MESA (Multi-Ethnic Study of Atherosclerosis). Multivessel CAC was defined by the number of coronary vessels with CAC (scored 1 to 4, including the left main). The "diffusivity index" was calculated as: 1 - (CAC in most affected vessel/total CAC), and was used to group participants into concentrated and diffuse CAC patterns. Multivariable Cox proportional hazards regression, area under the curve, and net reclassification improvement analyses were performed for both coronary heart disease (CHD) and cardiovascular disease (CVD) events to assess whether measures of regional CAC distribution add to the traditional Agatston CAC score.Mean age of the population was 66 ± 10 years, with 42% women. Median follow-up was 10.0 (9.5 to 10.7) years and there were 368 CHD and 493 CVD events during follow-up. Considerable heterogeneity existed between CAC score group and number of vessels with CAC (p < 0.01). Addition of number of vessels with CAC significantly improved capacity to predict CHD and CVD events in survival analysis (hazard ratio: 1.9 to 3.5 for 4-vessel vs. 1-vessel CAC), area under the curve analysis (C-statistic improvement of 0.01 to 0.033), and net reclassification improvement analysis (category-less net reclassification improvement 0.10 to 0.45). Although a diffuse CAC pattern was associated with worse outcomes in participants with ?2 vessels with CAC (hazard ratio: 1.33 to 1.41; p < 0.05), adding this variable to the Agatston CAC score and number of vessels with CAC did not further improve global risk prediction.The number of coronary arteries with calcified plaque, indicating increasingly "diffuse" multivessel subclinical atherosclerosis, adds significantly to the traditional Agatston CAC score for the prediction of CHD and CVD events.

Dataset Information

Activated TLR signaling in atherosclerosis among women with lower Framingham risk score: the multi-ethnic study of atherosclerosis.

Publications

Activated TLR signaling in atherosclerosis among women with lower Framingham risk score: the multi-ethnic study of atherosclerosis.

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