Author + information
- Received August 4, 2006
- Revision received September 22, 2006
- Accepted September 28, 2006
- Published online February 6, 2007.
- Karim El Harchaoui, MD⁎,
- Wim A. van der Steeg, MD⁎,
- Erik S.G. Stroes, MD, PhD⁎,
- Jan Albert Kuivenhoven, PhD⁎,
- James D. Otvos, PhD∥,1,
- Nicholas J. Wareham, MBBS, PhD‡,
- Barbara A. Hutten, PhD†,
- John J.P. Kastelein, MD, PhD⁎,⁎ (, )
- Kay-Tee Khaw, MBBChir§ and
- S. Matthijs Boekholdt, MD, PhD⁎
- ↵⁎Reprint requests and correspondence:
Dr. John J. P. Kastelein, F4.159-2, Department of Vascular Medicine, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
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.
↵1 Dr. Otvos is an employee of LipoScience, Inc.
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.
- Received August 4, 2006.
- Revision received September 22, 2006.
- Accepted September 28, 2006.
- American College of Cardiology Foundation