Value of low-density lipoprotein particle number and size as predictors of coronary artery disease in apparently healthy men and women: the EPIC-Norfolk Prospective Population Study.
OBJECTIVE
We assessed relations of low-density lipoprotein (LDL) particle number (LDL-P) and LDL particle size as measured by nuclear magnetic resonance spectroscopy with LDL cholesterol (LDL-C) and the risk of future coronary artery disease (CAD).


BACKGROUND
Whereas LDL-C is an established risk factor for CAD, its discriminative power is limited. Measuring LDL-P and size may have stronger associations with CAD than LDL-C.


METHODS
A nested case-control study was performed in the prospective EPIC (European Prospective Investigation into Cancer and Nutrition)-Norfolk study, which comprises 25,663 subjects. Cases (n = 1,003) were individuals who developed CAD during 6 year follow-up. Control subjects (n = 1,885) were matched for age, gender, and enrollment time. Odds ratios (ORs) for future CAD were calculated, and we also evaluated whether LDL-P could improve the Framingham risk score (FRS) to predict CAD.


RESULTS
In univariate analyses, LDL-P (OR 2.00, 95% confidence interval [CI] 1.58 to 2.59) and non-high-density lipoprotein cholesterol (non-HDL-C) (OR 2.14, 95% CI 1.69 to 2.69) were more closely associated with CAD than LDL-C (OR 1.73, 95% CI 1.37 to 2.18). The additional value of LDL-P was lost after adjustment for HDL-C and triglyceride levels. Whereas LDL size was inversely related to CAD (OR 0.60, 95% CI 0.47 to 0.76), this relation was abolished upon adjustment for LDL-P. In a model adjusted for the FRS, LDL-P retained its association with CAD (p for trend 0.02).


CONCLUSIONS
In this large study of individuals with moderately elevated LDL-C, LDL-P was related to CAD on top of FRS as well as after adjusting for LDL-C. The additional value of LDL-P was comparable to non-HDL-C, and it was abolished after adjusting for triglycerides and HDL-C.
El Harchaoui
Karim
K
Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
van der Steeg
Wim A
WA
Stroes
Erik S G
ES
Kuivenhoven
Jan Albert
JA
Otvos
James D
JD
Wareham
Nicholas J
NJ
Hutten
Barbara A
BA
Kastelein
John J P
JJ
Khaw
Kay-Tee
KT
Boekholdt
S Matthijs
SM
D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000737:chemistry; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood* / Q000737:chemistry*; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000097:blood* / Q000209:etiology; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood* / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
D015415:Biomarkers; D008077:Lipoproteins, LDL; D014280:Triglycerides; D002784:Cholesterol