Atherosclerosis, Plaque and CVD in Communities
Condition: Atherosclerosis; Cardiovascular Diseases; Heart Diseases; Cerebrovascular Accident; Coronary Arteriosclerosis; Coronary Disease
MeSH terms: Stroke; Cardiovascular Diseases; Heart Diseases; Atherosclerosis; Coronary Disease; Coronary Artery Disease; Arteriosclerosis; Myocardial Ischemia
Study type: Observational

Summary: 
      To identify new cellular, metabolic, and genomic correlates of atherosclerotic plaque and
      early pathologic changes in the vascular wall and determine their consequences for coronary
      heart disease and stroke.
    

Detailed description: 
      BACKGROUND:

      This study draws upon the existing ARIC cohort of 15,792 members aged 45-64 years at baseline
      in 1987-1989 who have completed four clinic exams three years apart with the last exam in
      1998. The longitudinal ARIC cohort study focused on new cardiovascular disease [CVD] risk
      factors and subclinical measures of atherosclerosis through B-mode ultrasound of the carotid
      arteries. The current study collects new and novel risk factors and performs carotid magnetic
      resonance imaging (MRI) examinations on a stratified random sample of 1,200 ARIC participants
      with high (>85th percentile) carotid intimal-medial thickness [IMT] by ultrasound and 800
      participants with <85th percentile IMT.

      DESIGN NARRATIVE:

      The study examines an informative subset of the bi-ethnic Atherosclerosis Risk in Communities
      (ARIC) cohort to identify cellular, metabolic and genomic correlates of atherosclerotic
      plaque characteristics and of early changes in the vascular wall. The longitudinal follow-up
      and stored DNA in ARIC will allow testing the ability of the genomic correlates of plaque
      characteristics to predict incident coronary heart disease and stroke. One thousand two
      hundred individuals with high (>85th percentile) carotid artery wall thickness documented by
      B-mode ultrasound and 800 individuals sampled from the remainder of the carotid artery wall
      thickness distribution (<85th percentile) will receive a contrast-enhanced carotid MRI
      examination. Standardized MRI measures will include carotid artery wall thickness, T2 signal
      intensity changes and percent contrast enhancement indicative of endothelial dysfunction, and
      for those with plaque, fibrous cap thickness, lipid core volume, and calcification. Novel
      cellular, metabolic and genomic measures will be collected and will be related to
      MRI-measurable plaque characteristics. In particular, flow cytometry will be used to measure
      monocyte and platelet presentation of cytokines, growth factors and adhesion molecules, and
      cell-cell aggregation. High throughput genotyping methods will be used to measure 5 to 7
      polymorphic sites in each of 150 positional, expressional and biologic candidate genes,
      permitting multilocus and haplotype genomic analyses. The depth and breadth of existing risk
      factor and lifestyle data, extensive follow-up since 1986-89, and accumulation of clinical
      outcomes, including coronary heart disease, stroke and arteriosclerosis, contribute
      additional strengths to the laboratory and MRI investigations. Inferences will be made both
      cross-sectionally and longitudinally, with a special emphasis on genotype plus environment
      interaction. The ARIC cohort is in an ideal age range for the research because of the
      frequent and documented occurrence of plaque and the spectrum of clinically relevant stages
      from plaque initiation to mature fibrosis, calcification and even erosion and near-rupture.
    

Observational model: Cohort
Time perspective: Other
Sampling method: Probability Sample
Study population: 
        The current study collects new and novel risk factors and performs carotid magnetic
        resonance imaging (MRI) examinations on a stratified random sample of 1,200 ARIC
        participants with high (>85th percentile) carotid intimal-medial thickness [IMT] by
        ultrasound and 800 participants with <85th percentile IMT.
      
Biospecimen description: 
      Stored DNA in Atherosclerosis Risk in Communities (ARIC) cohort study to test the ability of
      the genomic correlates of plaque characteristics to predict incident coronary heart disease
      and stroke.