Cardiovascular Diseases Clinical Trial
To test the hypothesis that the responsiveness of major and emerging cardiovascular disease risk factors to changes in diet composition clusters within families depending on genetic susceptibility factors.
BACKGROUND:
Reduction in risk of cardiovascular disease (CVD) through dietary change has considerable
potential for a beneficial impact on public health. On a population basis, moderation of
both lipid profiles and blood pressure can be accomplished readily with a prudent diet.
Nevertheless, individual response to dietary impact on CVD risk factors varies widely,
presumably as a result of genetic differences. In particular, Blacks who constitute a
subpopulation with documented increased risk of morbidity and mortality from CVD would
disproportionately benefit from interventions designed to maximize the impact of dietary
change tailored to individual genetic makeup. Therefore, study of the influence of diet on
CVD risk factors, along with enhanced understanding of the genetic components involved,
would greatly potentiate chronic disease interventions.
The study is conducted in response to a Request for Applications issued in October, 2001 on
the Interaction of Genes and the Environment in Shaping Risk Factors for Heart, Lung, Blood,
and Sleep Disorders.
DESIGN NARRATIVE:
Two-generational family lines will be identified in Blacks with elevated low density
lipoprotein-C (LDLC) in probands. The population will be fed a controlled diet contrasting
an established heart healthy regimen with a typical American one. Concomitant rigorous
genetic, anthropometric, and behavioral evaluation will provide data with which to analyze
individual differences in response to consistent dietary intake. In Specific Aim 1, Black,
two-generational, families will be recruited and provided interventional diets designed to
reduce (or not) LDL-C and blood pressure. In Specific Aim 2, non-genetic predictors of CVD
risk factor response will be identified through extensive assessments of baseline behavioral
characteristics, anthropometric features, and metabolic factors. In Specific Aim 3, the
underlying genetic factors that predispose to response (or the lack of) to dietary
interventions will be identified through the examination of polymorphisms in candidate genes
and the identification of susceptibility loci by linkage analyses. In Specific Aim 4,
interactions between diet, CVD risk factor response and genetic factors will be dissected
through measures of potential mediating metabolic pathways.
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