Prior studies found inverse associations between high-density-lipoprotein cholesterol (HDL-C) or apolipoprotein A-1 with cardiovascular disease (CVD). Whether this is consistent across levels of low-density-lipoprotein cholesterol (LDL-C) or total atherogenic particle burden (apolipoprotein B100) is less well studied, particularly in women.
To determine the association between HDL-C or apolipoprotein A-1 with CVD across a range of LDL-C or apolipoprotein B100.
Prospective cohort study.
The Women’s Healthy Study, a cohort of US female health professionals.
26,861 initially healthy women, age ≥ 45 years at study entry (1992–1995), followed for a mean of approximately 11 years.
Baseline lipids were measured directly, and apolipoproteins with immunoassays. Outcomes were incident total CVD (N=929), coronary events (N=602), and stroke (N=319).
In multivariable analyses, HDL-C and apolipoprotein A-1 were inversely associated with CVD and coronary events but not stroke. Adjusted coronary hazard ratios (HRs) for decreasing quintiles of HDL-C were 1.00, 1.23 (95% CI, 0.85–1.78), 1.42 (CI, 0.98–2.06), 1.90 (CI, 1.33–2.71), and 2.19 (CI, 1.51–3.19), P for linear trend<0.001; and for apolipoprotein A-1 1.00, 0.98 (CI, 0.71–1.35), 1.02 (CI, 0.72–1.44), 1.37 (CI, 0.98–1.90), and 1.58 (CI, 1.14–2.20), P for linear trend=0.005. Consistent inverse associations were found for HDL-C with coronary events across a range of LDL-C, including among women with low LDL-C. No associations were noted for HDL-C or apolipoprotein A-1 among women with low apolipoprotein B100 (<90 mg/dL).
Population of low risk women, small numbers of events in the lowest apolipoprotein B100 stratum, single baseline measurements, and potential residual confounding.
Consistent inverse associations were found for HDL-C with incident coronary events among women with a range of LDL-C. Among women with low total atherogenic particle burden (apolipoprotein B100<90 mg/dL), few events occurred and no associations were seen.