The genetic response to short-term interventions affecting cardiovascular function: rationale and design of the Heredity and Phenotype Intervention (HAPI) Heart Study.
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.
Mitchell
Braxton D
BD
Division of Endocrinology, Department of Medicine, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USA. bmitchel@medicine.umaryland.edu
McArdle
Patrick F
PF
Shen
Haiqing
H
Rampersaud
Evadnie
E
Pollin
Toni I
TI
Bielak
Lawrence F
LF
Jaquish
Cashell
C
Douglas
Julie A
JA
Roy-Gagnon
Marie-Hélène
MH
Sack
Paul
P
Naglieri
Rosalie
R
Hines
Scott
S
Horenstein
Richard B
RB
Chang
Yen-Pei C
YP
Post
Wendy
W
Ryan
Kathleen A
KA
Brereton
Nga Hong
NH
Pakyz
Ruth E
RE
Sorkin
John
J
Damcott
Coleen M
CM
O'Connell
Jeffrey R
JR
Mangano
Charles
C
Corretti
Mary
M
Vogel
Robert
R
Herzog
William
W
Weir
Matthew R
MR
Peyser
Patricia A
PA
Shuldiner
Alan R
AR
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*
D014280:Triglycerides; D001241:Aspirin