Magnetic Resonance Imaging of Intraplaque Hemorrhage and Plaque Lipid Content With Continued Lipid-Lowering Therapy: Results of a Magnetic Resonance Imaging Substudy in AIM-HIGH.

Background: Intraplaque hemorrhage (IPH) is associated with plaque progression and ischemic events, and plaque lipid content (% lipid core) predicts the residual atherosclerotic cardiovascular disease risk. This study examined the impact of IPH on lipid content change in the setting of intensive lipid-lowering therapy.

Methods: In total, 214 AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low High-Density Lipoprotein/High Triglycerides: Impact on Global Health Outcomes) participants with clinically established ASCVD and low high-density lipoprotein cholesterol received cartoid MRI at baseline and 2 years to assess changes in carotid morphology and composition.

Lp(a) (Lipoprotein(a)) Levels Predict Progression of Carotid Atherosclerosis in Subjects With Atherosclerotic Cardiovascular Disease on Intensive Lipid Therapy: An Analysis of the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes) Carotid Magnetic Resonance Imaging Substudy-Brief Report.

Objective: To assess whether Lp(a) (lipoprotein(a)) levels and other lipid levels were predictive of progression of atherosclerosis burden as assessed by carotid magnetic resonance imaging in subjects who have been treated with LDL-C (low-density lipoprotein cholesterol)-lowering therapy and participated in the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes).

Approach And Results: AIM-HIGH was a randomized, double-blind study of subjects with established vascular disease, elevated triglycerides, and low HDL-C (high-density lipoprotein cholesterol). One hundred fifty-two AIM-HIGH subjects underwent both baseline and 2-year follow-up carotid artery magnetic resonance imaging.

Carotid Plaque Lipid Content and Fibrous Cap Status Predict Systemic CV Outcomes: The MRI Substudy in AIM-HIGH.

Objectives: The aim of this study was to investigate whether and what carotid plaque characteristics predict systemic cardiovascular outcomes in patients with clinically established atherosclerotic disease.

Background: Advancements in atherosclerosis imaging have allowed assessment of various plaque characteristics, some of which are more directly linked to the pathogenesis of acute cardiovascular events compared to plaque burden.

Methods: As part of the event-driven clinical trial AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes), subjects with clinically established atherosclerotic disease underwent multicontrast carotid magnetic resonance imaging (MRI) to detect plaque tissue composition and high-risk features.

Clinical factors associated with high-risk carotid plaque features as assessed by magnetic resonance imaging in patients with established vascular disease (from the AIM-HIGH Study).

Association between clinical factors and high-risk plaque features, such as, thin or ruptured cap, intraplaque hemorrhage, presence of lipid-rich necrotic core (LRNC), and increased LRNC volume as assessed by magnetic resonance imaging (MRI), was examined in patients with established vascular disease in the Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides (AIM-HIGH) trial. A total of 214 subjects underwent carotid MRI and had acceptable image quality for assessment of plaque burden, tissue contents, and MRI-modified American Heart Association lesion type by a core laboratory. We found that 77% of subjects had carotid plaques, 52% had lipid-containing plaques, and 11% had advanced American Heart Association type-VI lesions with possible surface defect, intraplaque hemorrhage, or mural thrombus.

Paradoxical reduction in HDL-C with fenofibrate and thiazolidinedione therapy in type 2 diabetes: the ACCORD Lipid Trial.

Objective: To determine the occurrence of extremely low HDL cholesterol (HDL-C) among participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid Trial and to examine the relationship of this finding with treatment with fenofibrate and thiazolidinedione (TZD).

Research Design And Methods: The ACCORD Lipid Trial was a randomized, double-blind, placebo-controlled study conducted in patients with type 2 diabetes at 77 clinical centers across the U.S.

Effect of rosuvastatin on the echolucency of the common carotid intima-media in low-risk individuals: the METEOR trial.

Background: The echolucency of the carotid intima-media is related to increased cardiovascular risk factor levels, morbidity, and mortality. The aim of this study was to assess the effect of statins on the echolucency of the common carotid intima-media in a low-risk population.

Methods: Data from the Measuring Effects on Intima-Media Thickness: An Evaluation of Rosuvastatin study were used.

Biologically implausible carotid intima-media thickness measurement values: effects on rate of change over time.

Objective: Carotid intima-media thickness (CIMT) is a marker of atherosclerosis that is commonly used to assess the effect of therapeutic interventions. It is currently unclear to what extent biologically implausible values affect treatment effects. We evaluated the impact of biologically implausible CIMT values on the estimated rate of change in CIMT.

Multiple imputation of missing repeated outcome measurements did not add to linear mixed-effects models.

Objective: To assess the added value of multiple imputation (MI) of missing repeated outcomes measures in longitudinal data sets analyzed with linear mixed-effects (LME) models.

Study Design And Setting: Data were used from a trial on the effects of Rosuvastatin on rate of change in carotid intima-media thickness (CIMT). The reference treatment effect was derived from a complete data set.

Sample size requirements in trials using repeated measurements and the impact of trial design.

Objective: Sample size calculations for clinical trials generally use expected changes between groups, and variances obtained from the literature. However, this approach neglects the impact of differences in trial design. We studied the effects of variations in trial design on the required sample size.

Reversibility of fenofibrate therapy-induced renal function impairment in ACCORD type 2 diabetic participants.

Objective: To assess the reversibility of the elevation of serum creatinine levels in patients with diabetes after 5 years of continuous on-trial fenofibrate therapy.

Research Design And Methods: An on-drug/off-drug ancillary study to the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid Trial to investigate posttrial changes in serum creatinine and cystatin C. Eligible participants were recruited into a prospective, nested, three-group study based on retrospective on-trial serum creatinine levels: fenofibrate case subjects (n = 321, ≥ 20% increase after 3 months of therapy); fenofibrate control subjects (n = 175, ≤ 2% increase); and placebo control subjects (n = 565).

Extensive or restricted ultrasound protocols to measure carotid intima-media thickness: analysis of completeness rates and impact on observed rates of change over time.

Background: Ultrasound protocols to measure carotid intima-media thickness (CIMT) vary considerably with regard to carotid sites and angles that are assessed. Measurements from the carotid bifurcation and internal carotid artery are thought to be affected by large numbers of missing data. Actual published quantification of completeness rates and the relation with cardiovascular risk factors, however, is scarce.

Algorithms to measure carotid intima-media thickness in trials: a comparison of reproducibility, rate of progression and treatment effect.

Background: Current ultrasound protocols to measure carotid intima-media thickness (CIMT) in trials differ considerably. The best CIMT protocol would be one that combines high reproducibility, a large and precise estimate of the rate of CIMT progression and a large and precise estimate of the treatment effect. We performed a post-hoc analysis to determine the best algorithm for determining CIMT using data from the METEOR study, a randomized double-blind, placebo-controlled study of the effect of rosuvastatin on CIMT progression in 984 low coronary heart disease risk individuals with increased CIMT.

The use of plaque score measurements to assess changes in atherosclerotic plaque burden induced by lipid-lowering therapy over time: the METEOR study.

Aim: To evaluate whether plaque scoring measurements are able to track changes in atherosclerotic plaque burden over time and to study whether this is affected by lipid-lowering therapy.

Methods: Data used were from METEOR (Measuring Effects on Intima-Media Thickness: an Evaluation Of Rosuvastatin), a randomized controlled trial of rosuvastatin 40 mg among 984 low-risk patients with modest carotid intima-media thickening (CIMT). In this analysis, duplicate ultrasound images from 12 carotid sites were collected at the baseline and end of the study from 495 European patients and were evaluated for plaque presence and severity.

Asymmetrical distribution of atherosclerosis in the carotid artery: identical patterns across age, race, and gender.

Background: Small autopsy studies and clinical practice indicated that carotid atherosclerosis develops in an asymmetrical helical pattern coinciding with regions of low shear stress. We investigated the distribution of carotid atherosclerosis as determined by maximum carotid intima-media thickness (CIMT), to assess if we could confirm this atherosclerotic configuration across various populations with different cardiovascular risk.

Methods And Results: We used the individual baseline CIMT data from 3364 subjects from four recent international multicentre randomized controlled trials in which the carotid artery was systematically examined using the same ultrasound protocol and method to quantify CIMT.

Effect of number of ultrasound examinations on the assessment of carotid intima-media thickness changes over time: the example of the METEOR study.

Objective: To evaluate the effect of the number and positioning during follow-up of ultrasound examinations on the rate of change in carotid intima-media thickness (CIMT) using METEOR (Measuring Effects on Intima-Media Thickness: an Evaluation of Rosuvastatin) as an example.

Methods: METEOR was a randomized, placebo-controlled trial showing that rosuvastatin reduced progression of 2-year change in CIMT among low-risk patients with subclinical atherosclerosis. In the full METEOR protocol, ultrasound examinations were performed twice before randomization, once each at 6, 12, and 18 months after randomization, and then twice at the end of study at 24 months.

The association between chronic stress type and C-reactive protein in the multi-ethnic study of atherosclerosis: does gender make a difference?

The objective of this study is to examine how chronic stress in major life domains [relationship, work, sympathetic-caregiving, financial] relates to CVD risk, operationalized using the inflammatory marker C-Reactive Protein (CRP), and whether gender differences exist. Participants were 6,583 individuals aged 45-84 years, recruited as part of the Multi-Ethnic Study of Atherosclerosis. Demographic and behavioral factors, health history, and chronic stress were self-reported.

Factors associated with presence and extent of coronary calcium in those predicted to be at low risk according to Framingham risk score (from the Multi-Ethnic Study of Atherosclerosis).

Even among asymptomatic persons at low risk (<10%) according to the Framingham risk score, high coronary artery calcium (CAC) scores signify a greater predicted risk of coronary heart disease events. We sought to determine the noninvasive factors (without radiation exposure) significantly associated with CAC in low-risk, asymptomatic persons. In a cross-sectional analysis, we studied 3,046 participants from the Multi-Ethnic Study of Atherosclerosis at a low 10-year predicted risk (Framingham risk score <10%) of coronary heart disease events.

30-year trends in serum lipids among United States adults: results from the National Health and Nutrition Examination Surveys II, III, and 1999-2006.

Data from National Health and Nutrition Examination Survey (NHANES) II (1976 to 1980), NHANES III (1988 to 1994), and NHANES 1999 to 2006 were examined to assess trends in total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, triglycerides (TGs), lipid-lowering medication use, and obesity. Age-adjusted decreases in TC (210 to 200 mg/dl) and LDL cholesterol (134 to 119 mg/dl) were observed. Those with high TC showed a decrease of 9% from NHANES II to NHANES 1999 to 2006, whereas those with LDL cholesterol ≥160 mg/dl showed a decrease of 8%.

Effects of combination lipid therapy in type 2 diabetes mellitus.

Background: We investigated whether combination therapy with a statin plus a fibrate, as compared with statin monotherapy, would reduce the risk of cardiovascular disease in patients with type 2 diabetes mellitus who were at high risk for cardiovascular disease.

Methods: We randomly assigned 5518 patients with type 2 diabetes who were being treated with open-label simvastatin to receive either masked fenofibrate or placebo. The primary outcome was the first occurrence of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes.

The epidemiology of subclavian stenosis and its association with markers of subclinical atherosclerosis: the Multi-Ethnic Study of Atherosclerosis (MESA).

Background: Recent studies indicate that subclavian stenosis (SS), diagnosed by a large systolic blood pressure difference (SBPD) between the right and left brachial arteries, is associated with cardiovascular disease (CVD) risk factors and outcomes. We sought to describe the epidemiology of SS and determine its association with markers of subclinical CVD in the baseline cohort of the Multi-Ethnic Study of Atherosclerosis.

Methods: We defined SS by an absolute SBPD>or=15 mmHg.

Does baseline carotid intima-media thickness modify the effect of rosuvastatin when compared with placebo on carotid intima-media thickness progression? The METEOR study.

Background: Many studies have used carotid intima-media thickness (CIMT) measurement to study atherosclerosis and the efficacy of interventions. The placebo-controlled Measuring Effects on intima-media Thickness: an Evaluation Of Rosuvastatin (METEOR) study showed significant reduction in the progression rate of maximum CIMT with 2 years of lipid treatment in asymptomatic individuals with subclinical atherosclerosis.

Design: The present post-hoc subgroup analysis of METEOR was carried out to determine whether the effect of rosuvastatin treatment varied according to baseline CIMT level.

Predictive value of brachial flow-mediated dilation for incident cardiovascular events in a population-based study: the multi-ethnic study of atherosclerosis.

Background: Although brachial artery flow-mediated dilation (FMD) predicts recurrent cardiovascular events, its predictive value for incident cardiovascular disease (CVD) events in adults free of CVD is not well established. We assessed the predictive value of FMD for incident CVD events in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods And Results: Brachial artery FMD was measured in a nested case-cohort sample of 3026 of 6814 subjects (mean+/-SD age, 61.

Differences in carotid arterial morphology and composition between individuals with and without obstructive coronary artery disease: a cardiovascular magnetic resonance study.

Objective: We sought to determine differences with cardiovascular magnetic resonance (CMR) in the morphology and composition of the carotid arteries between individuals with angiographically-defined obstructive coronary artery disease (CAD, > or = 50% stenosis, cases) and those with angiographically normal coronaries (no lumen irregularities, controls).

Methods And Results: 191 participants (50.3% female; 50.

Interaction of age with lipoproteins as predictors of aortic valve calcification in the multi-ethnic study of atherosclerosis.

Background: Previous epidemiologic studies have shown that low-density lipoprotein is an independent risk factor for prevalent aortic valve calcification (AVC); however, to our knowledge, the interactions between plasma lipoprotein concentrations and age on the relative risks (RRs) for AVC prevalence and severity have not been examined in a large, racially and ethnically diverse cohort.

Methods: Using stepwise RR regression, the relationships of baseline fasting lipid levels and lipoprotein levels to baseline prevalence and severity of AVC were determined in 5801 non-statin-using participants in the Multi-Ethnic Study of Atherosclerosis (MESA).

Results: In age-stratified, adjusted analyses, the low-density lipoprotein-associated RRs (95% confidence intervals) for prevalent AVC were higher for younger compared with older participants (age 45-54 years, 1.