Cardiovascular Diseases Clinical Trial
To determine familial and non-familial causes for susceptibility to atherosclerosis and the inflammatory response.
BACKGROUND:
Atherosclerotic cardiovascular disease, along with its related health expenditures,
mortality, and morbidity, remains among the most significant health-related conditions in
the United States and other developed countries. The substantial resources that have been
expended to investigate this problem have led to significant scientific advances in the
basic biology, clinical management, epidemiology, and public health intervention approaches.
Despite these real advances, there remains much more to be done in terms of understanding
the basic biological and social processes, treatment, and public health programs.
Just as earlier research was effective in identifying a variety of epidemiologic risk
factors for cardiovascular disease, recent advances make it possible to bring to bear a
variety of new and powerful tools to detailed study of the basic processes involved in
atherogenesis. Application of these tools, in combination with synthesis of prior basic and
epidemiologic results, provides a powerful approach that is more model-driven than many
previous studies.
DESIGN NARRATIVE:
The Subclinical Atherosclerosis Network is a multicenter study of the genetic epidemiology
of coronary and aortic calcification and of inflammatory markers. It examines two areas of
great interest in contemporary vascular medicine, namely vascular calcification and
inflammation in approximately 3000 persons who have been recruited to the Family Heart
Study, with additional persons of African American descent contributed by the HyperGEN
Study. Considerable data, including a large number of genotypes, have been collected in the
Family Heart Study. The subjects will be brought back for additional data collection,
including the measurement of inflammatory markers and coronary and aortic calcification by
computed tomography (CT).
The network will quantify coronary and aortic artery calcium volume in 441 selected,
informative pedigrees ( approximately 3,000 individuals) previously examined and extensively
genotyped ( approximately 400 markers spanning the genome) by the NHLBI Family Heart Study,
in order to identify genes associated with human atherosclerosis. An additional 275 African
American sibships (approximately 600 individuals, also examined and comparably genotyped)
will be included to address these study questions in this high-risk population. Assessment
of the inter-individual variability in the inflammatory burden and the host response, and
the extensive metabolic, behavioral, and environmental data already collected on these
pedigrees will provide enhanced phenotypic homogeneity and increased analytic power in
assessing the genetic basis of atherosclerosis.
State of the art laboratory and statistical methods will be used to find, localize and
characterize the influence of predisposing genes to atherosclerosis and the inflammatory
response. Novel genetic analysis methods will be used to address the issues of phenotypic,
genetic and population heterogeneity, epistasis, complex interactions among the genetic and
environmental risk factors, and to optimize the detection of genomic regions affecting
phenotypic susceptibility.
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Observational Model: Family-Based, Time Perspective: Cross-Sectional
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