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High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies
D J Gordon1, J L Probstfield, R J Garrison
1Lipid Metabolism-Atherogenesis Branch, National Institutes of Health, Bethesda, Maryland, MD 20892.
Insights
Higher high-density lipoprotein cholesterol (HDLC) levels significantly reduce coronary heart disease risk in men and women. This consistent inverse relationship was observed across multiple large-scale studies, confirming HDLC
Area of Science:
- Cardiovascular epidemiology
- Lipid metabolism
- Public health
Background:
- The British Regional Heart Study (BRHS) previously suggested that the inverse relationship between high-density lipoprotein cholesterol (HDLC) and coronary heart disease (CHD) incidence diminishes with statistical adjustment.
- Previous findings indicated a potential confounding effect or a weaker association than initially presumed.
Purpose of the Study:
- To re-evaluate the association between HDLC levels and CHD incidence across multiple large cohort studies.
- To determine if the inverse relationship persists after adjusting for key cardiovascular risk factors.
Main Methods:
- Analysis of data from the Framingham Heart Study (FHS), Lipid Research Clinics Prevalence Mortality Follow-up Study (LRCF), Coronary Primary Prevention Trial (CPPT), and Multiple Risk Factor Intervention Trial (MRFIT).
- Utilized the proportional hazards model, adjusting for age, blood pressure, smoking, body mass index, and low-density lipoprotein cholesterol (LDLC).
- Focused on control groups in randomized trials (CPPT and MRFIT) and included both fatal and non-fatal outcomes where available.
Main Results:
- A 1-mg/dl increase in HDLC was associated with a significant 2% CHD risk reduction in men and a 3% reduction in women across FHS, CPPT, and MRFIT.
- In LRCF, a 1-mg/dl HDLC increment correlated with significant 3.7% (men) and 4.7% (women) decrements in cardiovascular disease mortality.
- Confidence intervals for risk decrements overlapped considerably, suggesting a consistent protective effect of HDLC.
Conclusions:
- A consistent inverse relationship exists between HDLC levels and coronary heart disease event rates, even after comprehensive statistical adjustment for major risk factors.
- HDLC is a significant protective factor against cardiovascular disease mortality.
- HDLC levels showed no significant association with non-cardiovascular disease mortality.
Abstract:
The British Regional Heart Study (BRHS) reported in 1986 that much of the inverse relation of high-density lipoprotein cholesterol (HDLC) and incidence of coronary heart disease was eliminated by covariance adjustment. Using the proportional hazards model and adjusting for age, blood pressure, smoking, body mass index, and low-density lipoprotein cholesterol, we analyzed this relation separately in the Framingham Heart Study (FHS), Lipid Research Clinics Prevalence Mortality Follow-up Study (LRCF) and Coronary Primary Prevention Trial (CPPT), and Multiple Risk Factor Intervention Trial (MRFIT). In CPPT and MRFIT (both randomized trials in middle-age high-risk men), only the control groups were analyzed. A 1-mg/dl (0.026 mM) increment in HDLC was associated with a significant coronary heart disease risk decrement of 2% in men (FHS, CPPT, and MRFIT) and 3% in women (FHS). In LRCF, where only fatal outcomes were documented, a 1-mg/dl increment in HDLC was associated with significant 3.7% (men) and 4.7% (women) decrements in cardiovascular disease mortality rates. The 95% confidence intervals for these decrements in coronary heart and cardiovascular disease risk in the four studies overlapped considerably, and all contained the range 1.9-2.9%. HDLC levels were essentially unrelated to non-cardiovascular disease mortality. When differences in analytic methodology were eliminated, a consistent inverse relation of HDLC levels and coronary heart disease event rates was apparent in BRHS as well as in the four American studies.