Genetic Epidemiology of Hypertriglyceridemia
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.
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.
Study Design
Observational Model: Natural History
Conditions
Cardiovascular Diseases
Status
Completed
Source
National Heart, Lung, and Blood Institute (NHLBI)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00005368
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Cardiovascular Diseases
Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.
Diagnostic Techniques, Cardiovascular
Methods and procedures for the diagnosis of diseases or dysfunction of the cardiovascular system or its organs or demonstration of their physiological processes.
Death, Sudden, Cardiac
Unexpected rapid natural death due to cardiovascular collapse within one hour of initial symptoms. It is usually caused by the worsening of existing heart diseases. The sudden onset of symptoms, such as CHEST PAIN and CARDIAC ARRHYTHMIAS, particularly VENTRICULAR TACHYCARDIA, can lead to the loss of consciousness and cardiac arrest followed by biological death. (from Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 7th ed., 2005)
Cardiovascular Physiological Phenomena
Processes and properties of the CARDIOVASCULAR SYSTEM as a whole or of any of its parts.
Dental Care For Chronically Ill
Dental care for patients with chronic diseases. These diseases include chronic cardiovascular, endocrinologic, hematologic, immunologic, neoplastic, and renal diseases. The concept does not include dental care for the mentally or physically disabled which is DENTAL CARE FOR DISABLED.
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