Joint Determinants of Bone Density and CVD Calcification
Condition: Atherosclerosis; Cardiovascular Diseases; Heart Diseases; Osteoporosis
MeSH terms: Osteoporosis; Cardiovascular Diseases; Heart Diseases; Atherosclerosis
Study type: Observational

Summary: 
      To evaluate the relationship bone marrow density and coronary artery and aortic
      calcification.
    

Detailed description: 
      BACKGROUND:

      There is growing evidence of a link between osteoporosis and atherosclerosis. Recent studies
      document that bone mineral density (BMD) is inversely correlated with severity of aortic and
      coronary artery calcification, markers of atherosclerosis. Cardiovascular disease and
      osteoporosis have tremendous negative public health impacts on the nation. Besides increased
      mortality, these negative impacts include severely diminished quality of life and huge
      financial burdens. With an ever aging population, this situation will get even worse. As
      increasing numbers of individuals now live well into their 80s and 90s, there is a great deal
      of interest on what has become known as healthy aging.

      The study is in response to a Request for Applications (RFA) entitled Bone Formation and
      Calcification in Cardiovascular Disease which was developed jointly with the National
      Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) to support research into
      the pathophysiology and molecular mechanisms of vascular calcification, and the possible
      links between vascular calcification, bone formation, and cardiovascular disease. The RFA was
      released in January, 2001.

      DESIGN NARRATIVE:

      The study evaluates the relationship between BMD and coronary artery and aortic
      calcification, measured by electron beam computed tomography, in 700 members of a large Amish
      pedigree already participating in the Amish Family Osteoporosis Study (AFOS). By focusing on
      families, the investigators hope to tease out the respective contributions of genetic and
      non-genetic factors to this clustering of traits. The AFOS was initiated in 1997 to identify
      genes influencing susceptibility to osteoporosis in families ascertained for fracture risk.
      Through NIH funding available to the AFOS parent study, the investigators will genotype 391
      highly polymorphic short tandem repeat (STR) markers spaced at approximately 10 cM intervals
      and perform a genome-wide scan to detect quantitative trait loci (QTLs) associated with
      variation in bone marrow density and related traits. The Old Order Amish are ideal for the
      studies since they are a closed founder population who are relatively genetically
      homogeneous, have very large family sizes, and well-documented genealogies. The study uses
      the available measures of bone marrow density, related traits, and genotypes in the AFOS
      along with the newly collected measures of vascular calcification.

      The specific goals are to determine if bone marrow density is correlated with coronary artery
      and aortic calcification (CAC) and, if so, to determine the contribution of common genes or
      shared environments to this association in families. The investigators will next assess
      genetic heritability and non-genetic contributions to variability in vascular calcification
      determinants of CAC in these families. They will assess the individual and joint
      contributions of lipid oxidation to bone marrow density and vascular calcification. Using the
      extensive genotyping that will be available, they will perform a genome wide scan of coronary
      artery and aortic calcification. These results will complement the similar analyses obtained
      on the bone-related phenotypes. Finally, they will determine if chromosomal regions linked to
      variation in bone marrow density are also linked to variation in vascular calcification or to
      another possible joint determinant such as CAC (or to lipid oxidation).
    

Observational model: Cohort
Time perspective: Cross-Sectional
Biospecimen description: 
      Plasma and serum samples.