title: The genetic response to short-term interventions affecting cardiovascular function: rationale and design of the Heredity and Phenotype Intervention (HAPI) Heart Study.
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.
authors.affiliation: Division of Endocrinology, Department of Medicine, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USA. bmitchel@medicine.umaryland.edu
authors.forename: Braxton D
authors.initials: BD
authors.lastname: Mitchell
authors.forename: Patrick F
authors.initials: PF
authors.lastname: McArdle
authors.forename: Haiqing
authors.initials: H
authors.lastname: Shen
authors.forename: Evadnie
authors.initials: E
authors.lastname: Rampersaud
authors.forename: Toni I
authors.initials: TI
authors.lastname: Pollin
authors.forename: Lawrence F
authors.initials: LF
authors.lastname: Bielak
authors.forename: Cashell
authors.initials: C
authors.lastname: Jaquish
authors.forename: Julie A
authors.initials: JA
authors.lastname: Douglas
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Roy-Gagnon
authors.forename: Paul
authors.initials: P
authors.lastname: Sack
authors.forename: Rosalie
authors.initials: R
authors.lastname: Naglieri
authors.forename: Scott
authors.initials: S
authors.lastname: Hines
authors.forename: Richard B
authors.initials: RB
authors.lastname: Horenstein
authors.forename: Yen-Pei C
authors.initials: YP
authors.lastname: Chang
authors.forename: Wendy
authors.initials: W
authors.lastname: Post
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Ryan
authors.forename: Nga Hong
authors.initials: NH
authors.lastname: Brereton
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Pakyz
authors.forename: John
authors.initials: J
authors.lastname: Sorkin
authors.forename: Coleen M
authors.initials: CM
authors.lastname: Damcott
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: O'Connell
authors.forename: Charles
authors.initials: C
authors.lastname: Mangano
authors.forename: Mary
authors.initials: M
authors.lastname: Corretti
authors.forename: Robert
authors.initials: R
authors.lastname: Vogel
authors.forename: William
authors.initials: W
authors.lastname: Herzog
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Weir
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Peyser
authors.forename: Alan R
authors.initials: AR
authors.lastname: Shuldiner
mesh_terms: D000328:Adult; D001241:Aspirin / Q000627:therapeutic use*; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D010641:Phenotype; D010974:Platelet Aggregation / Q000187:drug effects*; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood*
chemical_list: D014280:Triglycerides; D001241:Aspirin