Trial Information

BACKGROUND:

The diet-heart hypothesis, that high dietary saturated fat and cholesterol intake increase
the risk and high polyunsaturated fat reduces the risk of coronary heart disease in man is
supported by ecologic studies, by experiments in rodents and non-human primates, by
voluminous literature relating dietary factors to serum lipids, by several secondary
prevention trials, and by the Lipid Research Clinics Trial demonstrating a reduction in
coronary heart disease among participants assigned to cholestyramine.

Despite the substantial scientific interest and the obvious public health implications of
the diet and heart disease issue, relatively few observational cohort or case-control
investigations had been published prior to 1985. Although these observational studies were
not entirely consistent, taken collectively, they tended to provide important general
support for the diet-heart hypothesis. However, due to study design, limited numbers of
endpoints, or methods of analysis, many central questions remained unanswered. The most
important issue was the quantitative relationship between specific dietary factors and risk
of coronary heart disease.

DESIGN NARRATIVE:

In this prospective cohort study, participants completed a mailed general medical and health
questionnaire at baseline and an intensively validated semiquantitative food frequency
questionnaire (SFFQ). At one year, tissue specimens were collected and catalogued for
future nested case-control analyses of coronary heart disease risk in relation to levels of
calcium, selenium, and chromium. Follow-up questionnaires to update exposure information
and ascertain non-fatal endpoints were mailed at two-year intervals. All reported cases of
non-fatal myocardial infarction, stroke, and cancer were documented with hospital records
and/or pathology reports. Fatal events were ascertained with the National Death Index and
documented. To standardize SFFQ nutrient scores against measurements of absolute intake,
two one-week diet records were obtained from a random sample of 150 Boston-area
participants.

The study was renewed in 1991, 1997, and in 2003 to continue the follow-up of 51,529 male
health professionals. The cohort is followed by questionnaires mailed at two-year intervals
to update exposure information and ascertain nonfatal events. Complete dietary assessments
are included every four years.