Cardiovascular Diseases Clinical Trial
To assess the mode of inheritance of familial combined hyperlipidemia and familial primary hypoalphalipoproteinemia and to resolve genetic and familial environmental effects on several phenotypes of importance to coronary heart disease.
BACKGROUND:
Although coronary heart disease has long been known to aggregate in families, in 1986 little
was known about the relative importance of genetic and environmental factors. This was
partly due to the heterogeneous nature of the disease. Instead of analyzing complex
endpoints, the tendency had been to focus on the individual risk factors or phenotypes.
Plasma lipids and lipoproteins are heterogeneous risk factors that have been analyzed as
subgroups from a genetic epidemiological perspective. Attention turned to the familial
aggregation of risk factors, particularly the hyperlipidemias, hypertension, and diabetes.
In 1971, the National Heart and Lung Institute began a series of epidemiologic studies at
several North American sites under the Lipid Research Clinics Program. The Family Study was
designed to investigate the familial association of blood lipids, lipoproteins, and
dyslipoproteinemias. This study complemented and did not duplicate ongoing analysis of Lipid
Research Clinics data.
DESIGN NARRATIVE:
The study addressed seven phenotypes, all derived from fasting blood samples: total
cholesterol, total triglyceride, LDL-cholesterol, HDL-cholesterol, VLDL-cholesterol, uric
acid, and glucose levels. The data had already been collected at Lipid Research Clinics in
Cincinnati, Iowa, Oklahoma, Minneapolis, and Stanford. Univariate and bivariate segregation
analysis were conducted on the mode of inheritance of familial combined hyperlipidemia and
familial primary hypoalphalipoproteinemia. Path analysis was used to resolve cultural and
biological inheritance for each phenotype within each clinic and for resolution of
population heterogeneity among the five Lipid Research Clinics. A general bivariate path
model was used to analyze the associations among the various phenotypes. General models were
used to analyze temporal trends in family resemblance for the seven phenotypes.
The study completion date listed in this record was obtained from the "End Date" entered in
the Protocol Registration and Results System (PRS) record.
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