Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00005215 |
| Other study ID # |
1094 |
| Secondary ID |
R01HL038763 |
| Status |
Completed |
| Phase |
N/A
|
| First received |
May 25, 2000 |
| Last updated |
February 26, 2016 |
| Start date |
April 1988 |
| Est. completion date |
March 1992 |
Study information
| Verified date |
May 2000 |
| Source |
National Heart, Lung, and Blood Institute (NHLBI) |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
United States: Federal Government |
| Study type |
Observational
|
Clinical Trial Summary
To determine the relationship of fatal and nonfatal coronary heart disease to lipoprotein
fractions and other risk factors in a prospective epidemiologic study conducted between 1954
and 1957.
Description:
BACKGROUND:
Prospective epidemiologic studies of cholesterol, blood pressure, and cigarette use have
provided much of the evidence linking these established risk factors to coronary heart
disease, for example the Framingham Study, the Western Electric Study, and the Chicago
Peoples Gas Company Study. Concurrent to these well known studies, was an effort by Dr. John
Gofman to measure lipoprotein subfraction concentrations in 2,880 male and female employees
of the Lawrence Livermore National Laboratory, and to establish prospectively the
associations of HDL2, HDL3, LDL, IDL, smaller VLDL and larger VLDL to coronary heart
disease. After 10 years of follow-up, Dr. Gofman presented his findings at the Lyman Duff
Memorial Lecture on October 13, 1965. The findings were subsequently published in
Circulation in 1966. He reported an increased risk of coronary heart disease in association
with high serum mass concentrations of LDL, IDL, and smaller VLDL and low concentrations of
HDL2 and HDL3. This pioneering effort by Dr. Gofman preceded the recognition of the
importance of lipoprotein subfractions by nearly a decade, so that more detailed statistical
analyses and further follow-up of the cohort were deferred indefinitely. Most importantly,
in 1952 Gofman used essentially the same methodology to measure lipoprotein subfractions
that was in practice in 1988 at the Donner Laboratory for numerous in-house and
collaborative studies including the study of atherosclerotic progression in the Stanford
Coronary Risk Intervention Project, the effects of exercise and weight loss on lipoproteins
in the Stanford Exercise Training Study and Weight Control Projects, and metabolism and
genetic transmission as part of the Donner Laboratory NIH program project entitled
Lipoprotein Subclasses: Structure, Origin and Metabolism.
DESIGN NARRATIVE:
Serum lipoprotein subfraction concentrations were measured in 1,961 men and 423 women who
were employed or who applied for employment at Lawrence Livermore National Laboratory
between 1954 and 1957. Computer files were created by Dr. Gofman at Donner Laboratory for
epidemiologic studies of lipoprotein fractions. The files included name, age, gender and the
following medical information: cholesterol, lipoprotein subfraction concentrations, blood
pressure, weight, smoking history, hemoglobin, red and white blood cell counts, and blood
proteins. Dr. Gofman provided those computer files for this study. The vital status and the
history of coronary disease in the cohort were determined through state and national
mortality surveillance systems, public records, medical and hospital records, autopsy
reports, and telephone interviews with cohort members. All medical documents were examined
by a physician and endpoints assigned according to international diagnostic criteria.
The data were used to extend Dr. Gofman's initial study from 10 to 30 years of follow-up.
Survival analysis was used to assess the independent contributions of specific lipoprotein
subclasses to coronary disease while controlling for other risk factors. Other issues
examined were whether HDL2 and HDL3 showed different relationships to coronary disease,
whether the relationships of lipoprotein subfractions to coronary disease were independent
of other established risk factors, and whether measurements of lipoprotein subfraction
concentrations offered significant improvement over total cholesterol in predicting coronary
disease risk.
The study completion date listed in this record was obtained from the "End Date" entered in
the Protocol Registration and Results System (PRS) record.
