Clinical Implications of Discordance Between LDL Cholesterol and LDL Particle Number

Background—The amount of cholesterol per LDL particle is variable and related in part to particle size, with smaller particles carrying less cholesterol. This variability causes concentrations of LDL cholesterol (LDL-C) and LDL particles (LDL-P) to be discordant in many individuals. Methods—LDL-P measured by nuclear magnetic resonance (NMR) spectroscopy, calculated LDL-C, and carotid intima-media thickness (IMT) were assessed at baseline in the Multi-Ethnic Study of Atherosclerosis (MESA), a community-based cohort of 6814 persons free of clinical CVD at entry and followed for CVD events (n=319 during 5.5-year follow-up). Discordance, defined as values of LDL-P and LDL-C differing by ≥ 12 percentile units to give equal-sized concordant and discordant subgroups, was related to CVD events and to carotid IMT in models predicting outcomes for a 1 SD difference in LDL-C or LDL-P, adjusted for age, sex and race. © No copyright information found. Corresponding Author: David C. Goff, Jr., Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157-1063. Telephone: 336-716-9837 Fax: 336-716-4501 dgoff@wfubmc.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Financial Disclosures: This research was supported by contracts N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute. NMR lipoprotein particle analyses were donated by LipoScience, Inc. Drs. Otvos and Shalaurova are employees of LipoScience, Inc. Dr. Otvos is also a shareholder of LipoScience, serves as Chief Scientific Officer, and is a member of its Board of Directors. NIH Public Access Author Manuscript J Clin Lipidol. Author manuscript; available in PMC 2012 March 1. Published in final edited form as: J Clin Lipidol. 2011 ; 5(2): 105–113. doi:10.1016/j.jacl. 2011.02. 001. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript Results—LDL-C and LDL-P were associated with incident CVD overall: hazard ratios (HR [95% CI]) 1.20 [1.08, 1.34] and 1.32 [1.19, 1.47], respectively, but for those with discordant levels, only LDL-P was associated with incident CVD (HR: 1.45 [1.19, 1.78]) (LDL-C HR: 1.07 [0.88, 1.30])). IMT also tracked with LDL-P rather than LDL-C, i.e., adjusted mean IMT of 958, 932, and 917 μm in the LDL-P > LDL-C discordant, concordant, and LDL-P < LDL-C discordant subgroups, respectively, with the difference persisting after adjustment for LDL-C (p=0.002) but not LDL-P (p=0.60). Conclusions—For individuals with discordant LDL-C and LDL-P levels, the LDL-attributable atherosclerotic risk is better indicated by LDL-P.