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Applicability of cholesterol-lowering primary prevention trials to a general population: the framingham heart study
D M Lloyd-Jones1, C J O'Donnell, R B D'Agostino
1Framingham Heart Study, 5 Thurber St, Framingham, MA 01702, USA. peter@fram.nhlbi.nih.gov
Insights
Cholesterol-lowering drug trials excluded many people, especially women, with high triglycerides. This means current prevention strategies may not apply to the general population, requiring further research.
Area of Science:
- Cardiology
- Preventive Medicine
- Lipid Metabolism
Background:
- Four major trials demonstrated the efficacy of cholesterol-reduction therapy for primary prevention of coronary heart disease (CHD).
- The generalizability of these findings to broader community samples remains to be fully established.
Purpose of the Study:
- To assess the applicability of existing cholesterol-reduction trial eligibility criteria to a community-based population.
- To compare lipid profiles and CHD event rates between trial-eligible and ineligible subjects.
Main Methods:
- Comparison of lipid distributions (total cholesterol and HDL-C) between Framingham Heart Study participants and patients in four major CHD prevention trials.
- Identification of lipid profiles not studied in these trials.
- Analysis of 12-year incident CHD rates in relation to trial eligibility.
Main Results:
- A significant proportion of Framingham participants, particularly women, did not meet eligibility criteria for the analyzed trials.
- Many individuals who experienced CHD events, especially those with isolated hypertriglyceridemia, would have been excluded from trial participation.
- Specific lipid profiles, including desirable total cholesterol with low HDL-C, and average levels with higher HDL-C, were underrepresented in the trials.
Conclusions:
- A substantial percentage of men and women possess lipid profiles unexamined by current large-scale cholesterol-reduction trials.
- CHD events occurred frequently in "ineligible" subjects, often associated with hypertriglyceridemia, highlighting a gap in primary prevention knowledge.
- Further research is essential to determine optimal lipid-lowering strategies for the general population, considering individuals outside current trial parameters.
Background:
Four large trials have shown cholesterol-reduction therapy to be effective for primary prevention of coronary heart disease (CHD).
Methods:
To determine the generalizability of these trials to a community-based sample, we compared the total cholesterol and high-density lipoprotein cholesterol (HDL-C) distributions of patients in the 4 trials with those of Framingham Heart Study subjects. Lipid profiles that have not been studied were identified. Twelve-year rates of incident CHD were compared between subjects who met eligibility criteria and those who did not.
Results:
The Framingham sample included 2498 men and 2870 women aged 30 to 74 years. Among Framingham men, 23.4% to 42.0% met eligibility criteria for each of the 4 trials based on their lipid levels; 60.2% met eligibility criteria for at least 1 trial. For the 1 trial that included women, 20.2% of Framingham women met eligibility criteria. In general, subjects with desirable total cholesterol levels and lower HDL-C levels and subjects with average total cholesterol levels and average to higher HDL-C levels have not been included in these trials. Among subjects who developed incident CHD during follow-up, 25.1% of men and 66.2% of women would not have been eligible for any trial. Most ineligible subjects who developed CHD had isolated hypertriglyceridemia (>2.25 mmol/L [>200 mg/dL]).
Conclusions:
In our sample, 40% of men and 80% of women had lipid profiles that have not been studied in large trials to date. We observed a large number of CHD events in "ineligible" subjects in whom hypertriglyceridemia was common. Further studies are needed to define the role of lipid-lowering therapy vs other strategies for primary prevention in the general population.
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