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

Braxton D. Mitchell, Patrick F. McArdle, Haiqing Shen, Evadnie Rampersaud, Toni I. Pollin, Lawrence F. Bielak, Cashell Jaquish, Julie A. Douglas, Marie Hélène Roy-Gagnon, Paul Sack, Rosalie Naglieri, Scott Hines, Richard B. Horenstein, Yen Pei C. Chang, Wendy Post, Kathleen A. Ryan, Nga Hong Brereton, Ruth E. Pakyz, John Sorkin, Coleen M. DamcottJeffrey R. O'Connell, Charles Mangano, Mary Corretti, Robert Vogel, William Herzog, Matthew R. Weir, Patricia A. Peyser, Alan R. Shuldiner

Research output: Contribution to journalArticlepeer-review

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)823-828
Number of pages6
JournalAmerican heart journal
Volume155
Issue number5
DOIs
StatePublished - May 2008

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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