The genetic response to short-term interventions affecting cardiovascular function: Rationale and design of the Heredity and Phenotype Intervention (HAPI) Heart Study

Division of Endocrinology, Department of Medicine, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
American heart journal (Impact Factor: 4.46). 06/2008; 155(5):823-8. DOI: 10.1016/j.ahj.2008.01.019
Source: PubMed


The etiology of cardiovascular disease (CVD) is multifactorial. Efforts to identify genes influencing CVD risk have met with limited success to date, likely because of the small effect sizes of common CVD risk alleles and the presence of gene by gene and gene by environment interactions.
The HAPI Heart Study was initiated in 2002 to measure the cardiovascular response to 4 short-term interventions affecting cardiovascular risk factors and to identify the genetic and environmental determinants of these responses. The measurements included blood pressure responses to the cold pressor stress test and to a high salt diet, triglyceride excursion in response to a high-fat challenge, and response in platelet aggregation to aspirin therapy.
The interventions were carried out in 868 relatively healthy Amish adults from large families. The heritabilities of selected response traits for each intervention ranged from 8% to 38%, suggesting that some of the variation associated with response to each intervention can be attributed to the additive effects of genes.
Identifying these response genes may identify new mechanisms influencing CVD and may lead to individualized preventive strategies and improved early detection of high-risk individuals.

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    • "The features of the Amish discussed here have enabled the discovery and characterization of a unique mutation in the APOC3 gene, R19X, which in turn is providing access to biological insights previously unavailable. The Heredity and Phenotype Intervention (HAPI) Heart Study was begun in 2002 to evaluate the role of genetic and non-genetic risk factors in the response to four short-term interventions affecting cardiovascular risk factors (Mitchell et al. 2008). These interventions included: a single high-fat meal, a cold pressor stress test, a dietary intervention altering salt intake, and short-term aspirin therapy. "
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    • "The study was carried out in an Old Order Amish community in Lancaster County, PA, and the study sample included 868 individuals aged 20 years and older who were relatively healthy. Details of the study aims and recruitment procedures have been previously described [13]. Exclusion criteria included severe hypertension (blood pressure > 180/105 mmHg), malignancy, and kidney, liver or untreated thyroid disease. "
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