Abstract 18416: Discordance Between nonHDLc and Lipoprotein Particle Concentration (apoB and LDLp) in Relation to Future Coronary Events in Women

Abstract

Background: There remains equipoise as to which plasma lipid/lipoprotein marker most accurately reflects longitudinal risk of coronary heart disease (CHD) events. To compare differences in risk related to nonHDLc (atherogenic particle cholesterol) and LDL particle number (LDLp) or apoB (atherogenic particle number), we examined risk when these markers were discordant. Methods and Results: We divided 27,533 initially-healthy women in the Women’s Health Study (NCT00000479) into concordant/discordant groups based on median nonHDLc (154 mg/dL) and apoB (100 mg/dL) or 1 H NMR-measured LDLp (1,216 nmol/L). Discordance was defined as nonHDLc < median and the alternative measure ≥ median, or vice versa. We compared risks between concordant and discordant groups (using the concordant group as reference) with Cox proportional hazard models adjusted incrementally for: age; and randomization arm, hormone use, postmenopausal status, smoking, and hypertension (“minimally adjusted”); and diabetes, BMI, hsCRP, HDLc, triglycerides, and family history of CHD (“fully adjusted”). Although all 3 biomarkers were strongly correlated - nonHDLc and apoB (Spearman r=0.86, P<0.0001), nonHDLc and LDLp (r=0.77, P<0.0001), and apoB and LDLp (r=0.85, P<0.0001) - discordance between nonHDLc and apoB or LDLp occurred in 13.9% and 20.2% of women, respectively. A total of 1,246 CHD events occurred over median (max) 20.4 (21.7) years of follow-up (514,725 person-years). With nonHDLc < median (Fig. a), CHD risk was underestimated among women with discordant high apoB or LDLp: fully adjusted HR (95% CI) high apoB = 1.33 (1.04, 1.71); high LDLp = 1.27 (1.01, 1.61). Alternately, with nonHDLc ≥ median (Fig. b), CHD risk was overestimated among women with discordant low apoB or LDLp: fully adjusted HR [95% CI] low apoB = 0.74 (0.57, 0.96); low LDLp = 0.93 (0.76, 1.14). Conclusions: For women with discordant levels of nonHDLc with apoB or LDLp, CHD risk may be underestimated or overestimated with nonHDLc.