Clinical Research
Atherosclerosis
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

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Objectives

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.

Abbreviations and Acronyms

apoB
apolipoprotein B
BMI
body mass index
CAD
coronary artery disease
CI
confidence interval
FRS
Framingham risk score
HDL-C
high-density lipoprotein cholesterol
LDL
low-density lipoprotein
LDL-C
low-density lipoprotein cholesterol
LDL-P
low-density lipoprotein-particle number
NMR
nuclear magnetic resonance
OR
odds ratio

Cited by (0)

The EPIC-Norfolk study is supported by programmed grants from the Medical Research Council UK and Cancer Research UK, with additional support from the European Union, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and the Welcome Trust.

1

Dr. Otvos is an employee of LipoScience, Inc.