Clinical trial NCT00005168: Hyperapo B and Coronary Heart Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cardiovascular Diseases
Coronary Disease
Heart Diseases
Diabetes Mellitus
Obesity
Hypercholesterolemia, Familial
Lead sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Sponsor class: NIH
First posted: 2000-05-26
Sex: MALE
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no

Brief summary: To determine the role of apolipoprotein B and apolipoprotein A1 in the etiology of coronary artery disease.

Detailed description: BACKGROUND:

Hyperapo B is a phenotype defined as elevated plasma level of the major apoprotein B of low density lipoproteins in the presence of a normal plasma level of low density lipoprotein cholesterol. It has been demonstrated that hyperapo B is strongly associated with coronary artery disease. In 1984 when the study began, the independence of this association with other risk factors for coronary artery disease such as cigarette smoking, hypertension, and low plasma levels of high density lipoproteins was not known. The study improved knowledge of the pathophysiology of coronary artery disease and of the genetic and biochemical defects of hyperapo B and hypoalphalipoproteinemia.

DESIGN NARRATIVE:

Interviews were conducted and clinical data collected on each index case and spouse, as well as on first degree relatives. Risk factor data included blood pressure, blood lipid levels, obesity, cigarette smoking, fasting blood sugar and diabetes, hormone use and menopause for women, physical activity, personality scores, and family history. Clinical data included the indications for coronary arteriography, history of use of lipid-lowering agents and insulin, presence of corneal arcus, xanthomata, and xanthelasma, and the electrocardiogram.

To determine if the apolipoprotein B gene and the apolipoprotein A1-C3-A4 gene cluster were independent predictors of premature coronary disease, the relation between DNA polymeric sites within the two genes and coronary disease were investigated using cloned DNA fragments as molecular probes. To determine if apolipoprotein B and apolipoprotein A levels aggregated in families and to determine if hyperapo B and hypoalphalipoproteinemia segregated as Mendelian traits, genetic analysis was conducted in the 200 index cases and the 900 first degree relatives. Studies were also conducted on the linkages between hyperapo B and haplotypes of the apolipoprotein B gene, on hyperapo B and the Ag polymorphisms, and on hyperalphalipoproteinemia and haplotypes of the apolipoprotein A1-C3-A4 gene cluster.

The study completion date listed in this record was obtained from the "End Date" entered in the Protocol Registration and Results System (PRS) record.

Eligibility criteria: No eligibility criteria

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References:
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citation: Sniderman A, Teng B, Genest J, Cianflone K, Wacholder S, Kwiterovich P Jr. Familial aggregation and early expression of hyperapobetalipoproteinemia. Am J Cardiol. 1985 Feb 1;55(4):291-5. doi: 10.1016/0002-9149(85)90363-7.
citation: Teng B, Sniderman A, Krauss RM, Kwiterovich PO Jr, Milne RW, Marcel YL. Modulation of apolipoprotein B antigenic determinants in human low density lipoprotein subclasses. J Biol Chem. 1985 Apr 25;260(8):5067-72.
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citation: Prenger VL, Beaty TH, Kwiterovich PO. Genetic determination of high-density lipoprotein-cholesterol and apolipoprotein A-1 plasma levels in a family study of cardiac catheterization patients. Am J Hum Genet. 1992 Nov;51(5):1047-57.
citation: Coresh J, Beaty TH, Kwiterovich PO Jr, Antonarakis SE. Pedigree and sib-pair linkage analysis suggest the apolipoprotein B gene is not the major gene influencing plasma apolipoprotein B levels. Am J Hum Genet. 1992 May;50(5):1038-45.
citation: Kwiterovich PO Jr, Coresh J, Smith HH, Bachorik PS, Derby CA, Pearson TA. Comparison of the plasma levels of apolipoproteins B and A-1, and other risk factors in men and women with premature coronary artery disease. Am J Cardiol. 1992 Apr 15;69(12):1015-21. doi: 10.1016/0002-9149(92)90856-t.
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