Abstract
Background While ATP-III recommends measurement of total and HDL cholesterol (HDL-C) as part of coronary risk assessment, measurement of LDL particle number (LDL-P) is not currently recommended. Methods and Results In a prospective cohort of 27,673 initially healthy women, baseline LDL-P was measured by proton nuclear magnetic resonance spectroscopy, apolipoprotein B100 (ApoB) was measured using an immunoturbidimetric assay, and standard lipids were directly measured. LDL-P correlated with LDL cholesterol (LDL-C; r=0.62), ApoB (0.84), non HDL-C (0.74), and total:HDL-C ratio (0.80). During a mean follow-up of 11 years, 668 incident coronary heart disease (CHD) events occurred. Using the lowest quintile as the reference, and adjusting for age, smoking, blood pressure, diabetes, menopause, hormone use, and body mass index, the association of LDL-P with CHD was stronger than LDL-C (Table ), and comparable in magnitude to ApoB, non HDL-C and total:HDL-C ratio. In a subgroup analysis of women with LDL-C<100 mg/dL, elevations in LDL-P, ApoB, non HDL-C, or total:HDL-C ratio were all separately associated with higher CHD risk (P<0.001 for all). Both LDL-P and ApoB remained associated with CHD after additionally adjusting for total cholesterol, HDL-C, and triglycerides (hazard ratios for top vs bottom quintile: 2.03 [95% CI 1.27–3.24] for LDL-P, and 3.08 [95% CI 1.92– 4.93] for ApoB) overall, and similarly in women with LDL-C<100 mg/dL (2.77 [95%CI 1.05–7.29] for LDL-P and 2.62 [95%CI 0.97–7.05] for ApoB). Conclusions In this large-scale prospective cohort, elevations in NMR-measured LDL particle number were significantly associated with incident CHD, with a magnitude of risk not substantially different from ApoB, non HDL-C, or total:HDL-C ratio. Among women with LDL-C <100mg/dL, elevations in LDL-P, ApoB, non HDL-C, and total:HDL-C ratio all carried higher CHD risk. Risk Factor-Adjusted Hazard Ratios for Incident CHD
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