High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies.

TLDR

The British Regional Heart Study showed that the inverse association between high‑density lipoprotein cholesterol and coronary heart disease largely disappeared after adjusting for covariates, highlighting the need to clarify this relationship. The authors applied proportional‑hazards models adjusting for age, blood pressure, smoking, BMI, and LDL cholesterol to analyze HDLC’s effect on coronary heart disease in the Framingham, LRCF, CPPT, and MRFIT studies, using only control groups in the randomized trials. Across the four American studies, each 1‑mg/dl increase in HDLC was linked to a 2% risk reduction in men and 3% in women, with fatal‑outcome analyses showing 3.7% and 4.7% decreases, and confidence intervals overlapping 1.9–2.9%, confirming a consistent inverse relation while HDLC was unrelated to non‑cardiovascular 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.