Comparison of Two Methods to Diagnose Coronary Artery Disease
Condition: Cardiovascular Diseases; Coronary Disease; Heart Diseases
MeSH terms: Cardiovascular Diseases; Heart Diseases; Coronary Disease; Coronary Artery Disease
Study type: Observational

Summary: 
      The purpose of this study is to compare two methods of diagnosing coronary artery disease
      (CAD), thallium single photon emission computed tomography (SPECT) and ultrafast computed
      tomography (CT).
    

Detailed description: 
      BACKGROUND:

      The ability to noninvasively detect CAD at a subclinical stage is fundamental to
      understanding the biology of the transition of occult CAD to clinical CAD in asymptomatic
      people at the highest risk for future CAD.

      DESIGN NARRATIVE:

      The cross-sectional study is designed to identify the factors explaining why some individuals
      have exercise ischemia without significant coronary artery calcium (CAC) while others have
      extensive CAC without exercise ischemia. The investigators will compare the
      pathophysiological features of a functional test for subclinical CAD detection (exercise
      radionuclide perfusion SPECT) and an anatomical test to detect coronary calcification
      (ultrafast CT) in a high-risk asymptomatic population of 30 to 59 year old siblings of people
      with premature CAD. Siblings will undergo screening for occult CAD using both detection
      methods. Individuals who are abnormal on either test (exercise-induced ischemia or calcium
      score greater than 75th percentile for age and sex) will be offered cardiac catheterization,
      which will include quantitative coronary angiography, assessment of endothelial function by
      intracoronary acetylcholine, and measurement of plaque volume and composition in a selected
      coronary artery by intravascular ultrasound (IVUS). The study will focus on the
      pathophysiology of occult CAD among individuals who have exercise ischemia with low calcium
      scores and other individuals who have high calcium scores without ischemia. Discrepancies
      between these two tests measure potentially different biological pathways and such
      discrepancies are observed frequently in high-risk asymptomatic siblings (40% in our recent
      pilot study). Analyses will be done to determine which biological risk factors can account
      for variation in plaque calcification that results in discordances between these two measures
      of occult disease (including lipid levels and subclasses, Lp(a), diabetes, thrombotic
      factors, pro-inflammatory cytokines, and importantly, those factors involved in calcium
      regulation, and bone regulatory proteins). In those siblings undergoing cardiac
      catheterization, analyses will be done to determine whether the severity or extent of
      coronary luminal narrowing, the presence of epicardial or microvascular endothelial
      dysfunction, or the volume or calcium content of plaque by IVUS can account for discordances
      between the two screening tests. Polymorphisms in several candidate genes that may affect
      tissue calcification will be examined as a possible explanation for variations in plaque
      calcification as reflected in test discordance. Plasma and DNA will also be collected for
      novel studies of factors that may account for variability in coronary plaque calcification in
      this unique well characterized asymptomatic high risk population. This will be the first
      comprehensive study to define the unique biological and genetic factors related to occult
      CAD, as detected by both perfusion imaging and ultrafast CT.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Healthy siblings of patients with early onset CAD (<age 60) or the adult offspring of the
        siblings or probands, all participants in the GeneSTAR study.
      
Biospecimen description: 
      Blood