Genetic Epidemiology of Hypertriglyceridemia
Primary Purpose
Cardiovascular Diseases, Coronary Disease, Hyperlipidemia, Familial Combined
Status
Completed
Phase
Locations
Study Type
Observational
Intervention
Sponsored by
About this trial
This is an observational trial for Cardiovascular Diseases
Eligibility Criteria
No eligibility criteria
Sites / Locations
Outcomes
Primary Outcome Measures
Secondary Outcome Measures
Full Information
NCT ID
NCT00005368
First Posted
May 25, 2000
Last Updated
February 8, 2016
Sponsor
University of Washington
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
1. Study Identification
Unique Protocol Identification Number
NCT00005368
Brief Title
Genetic Epidemiology of Hypertriglyceridemia
Study Type
Observational
2. Study Status
Record Verification Date
January 2005
Overall Recruitment Status
Completed
Study Start Date
July 1993 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
August 2003 (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
University of Washington
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
4. Oversight
5. Study Description
Brief Summary
To determine prospectively the role of elevated plasma triglyceride (TG) as a risk factor for 20-year coronary heart disease (CHD) mortality in familial combined hyperlipidemia (FCHL) and familial hypertriglyceridemia (FHTG), the familial forms of hypertriglyceridemia. Also, to perform genetic epidemiologic studies of recently identified lipoprotein risk factors for CHD, including Atherogenic Lipoprotein Phenotypes (ALP) based on subclasses of low-density lipoproteins (LDL), Lipoprotein(a) (Lp(a)) and apolipoprotein (apo) B plasma levels, and apo E isoforms.
Detailed Description
BACKGROUND:
The study provided valuable new data on the role of triglyceride as a risk factor for coronary heart disease and on the genetic epidemiology of lipoprotein risk factors, using the only existing sample of families with hypertriglyceridemia that could be studied prospectively.
DESIGN NARRATIVE:
Using a sample of 101 families identified and studied in Seattle in the early 1970s, the study sought to determine if 20-year CHD mortality and all-cause mortality were increased in siblings and offspring of probands from families with familial combined hyperlipidemia and familial hypertriglyceridemia, compared to a group of married-in spouse controls. The study also sought to determine if elevated plasma triglycerides at baseline predicted 20-year CHD mortality in these family members. Based on new blood samples from these same families, the inheritance of LAP phenotypes was investigated, the association of elevated plasma Lp(a) and apo B levels with parental CHD mortality was examined, and the association of lipid levels with apo E isoforms was investigated. A repository of frozen white blood cells and plasma aliquots for future genetic studies was established.. These hypotheses were addressed by determining the vital status of 1009 family members in the 101 families, carefully classifying the cause of death as CHD or not for deceased family members, and by obtaining new blood samples from three generations of these families, including both local and non-local relatives. New personal and family history medical questionnaires were also completed for each participant.
The study was renewed in FY 1997 through June 30, 2001. The study has three new specific aims: to elucidate the genetic basis of small, dense, low-density lipoprotein, to map the chromosomal location(s) of gene(s) influencing this phenotype using a whole genome screen; to reveal common genetic influences (pleiotropic effects) on combinations of interrelated lipoprotein risk factors; and to evaluate familial CVD risk by determining the association between CVD in the proband generation and lipoprotein phenotypes, including lipoprotein(a) in the younger offspring generation in specific forms of familial hyperlipidemia.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiovascular Diseases, Coronary Disease, Hyperlipidemia, Familial Combined, Hyperlipoproteinemia Type iv
7. Study Design
10. Eligibility
Sex
Male
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
No eligibility criteria
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Melissa Austin
Organizational Affiliation
University of Washington
12. IPD Sharing Statement
Citations:
PubMed Identifier
7947591
Citation
Jarvik GP, Brunzell JD, Austin MA, Krauss RM, Motulsky AG, Wijsman E. Genetic predictors of FCHL in four large pedigrees. Influence of ApoB level major locus predicted genotype and LDL subclass phenotype. Arterioscler Thromb. 1994 Nov;14(11):1687-94. doi: 10.1161/01.atv.14.11.1687.
Results Reference
background
PubMed Identifier
8836866
Citation
Hokanson JE, Austin MA. Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk. 1996 Apr;3(2):213-9.
Results Reference
background
PubMed Identifier
8818515
Citation
Austin MA, Edwards KL. Small, dense low density lipoproteins, the insulin resistance syndrome and noninsulin-dependent diabetes. Curr Opin Lipidol. 1996 Jun;7(3):167-71. doi: 10.1097/00041433-199606000-00010.
Results Reference
background
PubMed Identifier
7712044
Citation
Austin MA, Hokanson JE, Brunzell JD. Characterization of low-density lipoprotein subclasses: methodologic approaches and clinical relevance. Curr Opin Lipidol. 1994 Dec;5(6):395-403. doi: 10.1097/00041433-199412000-00002.
Results Reference
background
PubMed Identifier
7894041
Citation
Austin MA. Small, dense low-density lipoprotein as a risk factor for coronary heart disease. Int J Clin Lab Res. 1994;24(4):187-92. doi: 10.1007/BF02592460.
Results Reference
background
PubMed Identifier
10521376
Citation
Edwards KL, Mahaney MC, Motulsky AG, Austin MA. Pleiotropic genetic effects on LDL size, plasma triglyceride, and HDL cholesterol in families. Arterioscler Thromb Vasc Biol. 1999 Oct;19(10):2456-64. doi: 10.1161/01.atv.19.10.2456.
Results Reference
background
PubMed Identifier
10859281
Citation
Austin MA, McKnight B, Edwards KL, Bradley CM, McNeely MJ, Psaty BM, Brunzell JD, Motulsky AG. Cardiovascular disease mortality in familial forms of hypertriglyceridemia: A 20-year prospective study. Circulation. 2000 Jun 20;101(24):2777-82. doi: 10.1161/01.cir.101.24.2777.
Results Reference
background
PubMed Identifier
11122745
Citation
Austin MA. Triglyceride, small, dense low-density lipoprotein, and the atherogenic lipoprotein phenotype. Curr Atheroscler Rep. 2000 May;2(3):200-7. doi: 10.1007/s11883-000-0021-4.
Results Reference
background
PubMed Identifier
12172393
Citation
Austin MA, Zimmern RL, Humphries SE. High "population attributable fraction" for coronary heart disease mortality among relatives in monogenic familial hypercholesterolemia. Genet Med. 2002 Jul-Aug;4(4):275-8. doi: 10.1097/00125817-200207000-00005.
Results Reference
background
PubMed Identifier
11730829
Citation
McNeely MJ, Edwards KL, Marcovina SM, Brunzell JD, Motulsky AG, Austin MA. Lipoprotein and apolipoprotein abnormalities in familial combined hyperlipidemia: a 20-year prospective study. Atherosclerosis. 2001 Dec;159(2):471-81. doi: 10.1016/s0021-9150(01)00528-7.
Results Reference
background
PubMed Identifier
11595020
Citation
Kim H, Marcovina SM, Edwards KL, McKnight B, Bradley CM, McNeely MJ, Psaty BM, Motulsky AG, Austin MA. Lipoprotein(a) as a risk factor for maternal cardiovascular disease mortality in kindreds with familial combined hyperlipidemia or familial hypertriglyceridemia. Clin Genet. 2001 Sep;60(3):188-97. doi: 10.1034/j.1399-0004.2001.600304.x.
Results Reference
background
PubMed Identifier
11384949
Citation
Kamigaki AS, Siscovick DS, Schwartz SM, Psaty BM, Edwards KL, Raghunathan TE, Austin MA. Low density lipoprotein particle size and risk of early-onset myocardial infarction in women. Am J Epidemiol. 2001 May 15;153(10):939-45. doi: 10.1093/aje/153.10.939.
Results Reference
background
PubMed Identifier
12923221
Citation
Austin MA, Edwards KL, Monks SA, Koprowicz KM, Brunzell JD, Motulsky AG, Mahaney MC, Hixson JE. Genome-wide scan for quantitative trait loci influencing LDL size and plasma triglyceride in familial hypertriglyceridemia. J Lipid Res. 2003 Nov;44(11):2161-8. doi: 10.1194/jlr.M300272-JLR200. Epub 2003 Aug 16.
Results Reference
background
PubMed Identifier
12750118
Citation
Ayyobi AF, McGladdery SH, McNeely MJ, Austin MA, Motulsky AG, Brunzell JD. Small, dense LDL and elevated apolipoprotein B are the common characteristics for the three major lipid phenotypes of familial combined hyperlipidemia. Arterioscler Thromb Vasc Biol. 2003 Jul 1;23(7):1289-94. doi: 10.1161/01.ATV.0000077220.44620.9B. Epub 2003 May 15.
Results Reference
background
PubMed Identifier
15321839
Citation
Hutter CM, Austin MA, Humphries SE. Familial hypercholesterolemia, peripheral arterial disease, and stroke: a HuGE minireview. Am J Epidemiol. 2004 Sep 1;160(5):430-5. doi: 10.1093/aje/kwh238.
Results Reference
background
PubMed Identifier
15321838
Citation
Austin MA, Hutter CM, Zimmern RL, Humphries SE. Familial hypercholesterolemia and coronary heart disease: a HuGE association review. Am J Epidemiol. 2004 Sep 1;160(5):421-9. doi: 10.1093/aje/kwh237.
Results Reference
background
PubMed Identifier
15321837
Citation
Austin MA, Hutter CM, Zimmern RL, Humphries SE. Genetic causes of monogenic heterozygous familial hypercholesterolemia: a HuGE prevalence review. Am J Epidemiol. 2004 Sep 1;160(5):407-20. doi: 10.1093/aje/kwh236.
Results Reference
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Genetic Epidemiology of Hypertriglyceridemia
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