Ignite Creation Date:
2024-05-05 @ 7:24 PM
Last Modification Date:
2024-10-26 @ 9:48 AM
Study NCT ID:
NCT00664040
Status:
COMPLETED
Last Update Posted:
2022-07-26
First Post:
2008-04-18
Brief Title:
Heredity and Phenotype Intervention HAPI Heart Study
Sponsor:
University of Maryland Baltimore
Organization:
University of Maryland Baltimore
Study Overview
Official Title:
Heredity and Phenotype Intervention HAPI Heart Study
Status:
COMPLETED
Status Verified Date:
2022-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
HAPI
Brief Summary:
Cardiovascular disease CVD is the leading cause of death in the United States and many people that die of heart disease have no previous symptoms This study will look specifically at the response to four short-term environmental exposures including the bodys response to a cold stimulus to a high fat milk shake to aspirin and to a high and low salt diet These interventions are all known to influence CVD and people can have different responses to these interventions which may be due at least in part to differences in genetic make up
Detailed Description:
Nearly one million Americans died of CVD in 1999 and it is predicted that over one million Americans will have a myocardial infarction MI with 650000 of these experiencing their first MI Coronary artery disease CAD is the leading cause of mortality in the US accounting for 1 of every 5 deaths or 680000 of more than 2000000 deaths CAD is also the leading cause of premature permanent disability in the US labor force accounting for more than 110 billion in health care costs annually as compared to 329 billion for all CVD Risk factors for CAD include high blood pressure tobacco smoke abnormal lipids and lipoproteins physical inactivity overweight and obesity diabetes mellitus increasing age male sex heredity individual response to stress and menopause in women Other indicators for increased risk of events include the presence and extent of coronary artery calcification endothelial dysfunction and platelet aggregation Of those who die suddenly from CAD 50 of men and 63 of women have no previous symptoms Studies of how specific environmental interventions may interact with genes to influence selected risk factors especially in individuals with varying extent of vascular calcification a marker of atherosclerosis will facilitate the early identification of asymptomatic high-risk individuals who will benefit from existing or new interventions
The overall objective of this proposal is to identify novel loci and ultimately genes that interact with specific environmental exposures to modify risk factors for cardiovascular disease CVD To achieve this goal we will perform four short-term interventions known to modify CVD risk in participants of the Amish Family Calcification Study AFCS an ongoing study of the joint genetic determinants of CVD and osteoporosis Over 1000 individuals from this ongoing study have already been recruited and are being characterized with respect to CVD risk factors including blood pressure body composition lipids and coronary artery calcification by electron beam computerized tomography EBCT From a previous examination DNA has been collected on all AFCS subjects and a 5-cM genome scan 800 short tandem repeat STR markers has been completed by the NHLBI Mammalian Genotyping Service Thus this large family study from a unique genetically homogeneous founder population provides an ideal opportunity to identify genes that interact with the environment in shaping risk factors for CVD The Specific Aims of this proposal are
1 To perform four focused short-term interventions known to affect cardiovascular function in 1000 subjects from the AFCS Responses of relevant CVD-related quantitative traits will be measured The interventions and responses will be a cold pressor stress and changes in blood pressure and changes in endothelial function as assessed by brachial artery dilation BART b a high fat load and changes in brachial artery flow mediated dilation FMD and serum lipid levels c high salt and low salt diets and changes in blood pressure and d aspirin and changes in platelet function and inflammatory markers
2 To characterize the genetic epidemiology of the responses to each short-term intervention by a estimating the heritability of each response to the intervention b determining if response to intervention is correlated with coronary artery and aortic calcification and if so if the association can be explained by common genes or shared environments and c determining if response to intervention is correlated with baseline measures of CVD risk factors and if so if the association can be explained by common genes or shared environments
3 To identify specific chromosomal loci that influence CVD-related trait responses to the four short-term interventions by performing genome-wide linkage analysis utilizing a 5 cM density 800 STR markers genetic map already available in 1000 subjects of the AFCS
4 To determine if chromosomal regions linked to or associated with variation in CVD-related trait responses are also linked to or associated with variation in coronary artery or aortic calcification
5 To fine map the putative chromosomal loci linked to variation in CVD-related trait responses to short-term environmental interventions through linkage disequilibrium mapping with closely spaced single nucleotide polymorphism SNP markers
The overall objective of this proposal is to identify novel loci and ultimately genes that interact with specific environmental exposures to modify risk factors for cardiovascular disease CVD To achieve this goal we will perform four short-term interventions known to modify CVD risk in participants of the Amish Family Calcification Study AFCS an ongoing study of the joint genetic determinants of CVD and osteoporosis Over 1000 individuals from this ongoing study have already been recruited and are being characterized with respect to CVD risk factors including blood pressure body composition lipids and coronary artery calcification by electron beam computerized tomography EBCT From a previous examination DNA has been collected on all AFCS subjects and a 5-cM genome scan 800 short tandem repeat STR markers has been completed by the NHLBI Mammalian Genotyping Service Thus this large family study from a unique genetically homogeneous founder population provides an ideal opportunity to identify genes that interact with the environment in shaping risk factors for CVD The Specific Aims of this proposal are
1 To perform four focused short-term interventions known to affect cardiovascular function in 1000 subjects from the AFCS Responses of relevant CVD-related quantitative traits will be measured The interventions and responses will be a cold pressor stress and changes in blood pressure and changes in endothelial function as assessed by brachial artery dilation BART b a high fat load and changes in brachial artery flow mediated dilation FMD and serum lipid levels c high salt and low salt diets and changes in blood pressure and d aspirin and changes in platelet function and inflammatory markers
2 To characterize the genetic epidemiology of the responses to each short-term intervention by a estimating the heritability of each response to the intervention b determining if response to intervention is correlated with coronary artery and aortic calcification and if so if the association can be explained by common genes or shared environments and c determining if response to intervention is correlated with baseline measures of CVD risk factors and if so if the association can be explained by common genes or shared environments
3 To identify specific chromosomal loci that influence CVD-related trait responses to the four short-term interventions by performing genome-wide linkage analysis utilizing a 5 cM density 800 STR markers genetic map already available in 1000 subjects of the AFCS
4 To determine if chromosomal regions linked to or associated with variation in CVD-related trait responses are also linked to or associated with variation in coronary artery or aortic calcification
5 To fine map the putative chromosomal loci linked to variation in CVD-related trait responses to short-term environmental interventions through linkage disequilibrium mapping with closely spaced single nucleotide polymorphism SNP markers
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| HP-00040375 | OTHER | University of Maryland Baltimore | httpsreporternihgovquickSearchU01HL072515-05 |
| U01HL072515 | NIH | None | None |
| U01HL072515-05 | NIH | None | None |