Wim A. van der Steeg, MD; S. Matthijs Boekholdt, MD, PhD; Evan A. Stein, MD, PhD; Karim El-Harchaoui, MD; Erik S.G. Stroes, MD, PhD; Manjinder S. Sandhu, PhD; Nicholas J. Wareham, MBBS, PhD; J. Wouter Jukema, MD, PhD; Robert Luben, BSc; Aeilko H. Zwinderman, PhD; John J.P. Kastelein, MD, PhD; Kay-Tee Khaw, MBBChir
Note: Drs. van der Steeg and Boekholdt contributed equally to this study.
Acknowledgments: The authors thank the participants, general practitioners, and staff in EPIC-Norfolk.
Grant Support: The EPIC-Norfolk is supported by program grants from the Medical Research Council (United Kingdom) and Cancer Research UK and receives additional support from the European Union, Stroke Association, British Heart Foundation, United Kingdom Department of Health, Food Standards Agency, and the Wellcome Trust. Part of the lipid and apolipoprotein measurements described in this article were funded by an educational grant from the Future Forum. Dr. Kastelein is an established investigator (2000 D039) and Dr. Jukema is an established clinical investigator (2001 D032) of the Netherlands Heart Foundation, The Hague, the Netherlands.
Potential Financial Conflicts of Interest: None disclosed.
Requests for Single Reprints: John J.P. Kastelein, MD, PhD, Department of Vascular Medicine, Academic Medical Center, Room F4-159.2, PO Box 22660, 1100 DD Amsterdam, the Netherlands; e-mail, email@example.com.
Current Author Addresses: Drs. van der Steeg, Boekholdt, El-Harchaoui, Stroes, and Kastelein: Department of Vascular Medicine, Academic Medical Center, Room F4-159.2, PO Box 22660, 1100 DD Amsterdam, the Netherlands.
Dr. Stein: Metabolic & Atherosclerosis Research Center, Suite 201, 3131 Harvey Avenue, Cincinnati, OH 45229.
Drs. Sandhu, Luben, and Khaw: Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, F & G Block, Level 2, Box 251, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, United Kingdom.
Dr. Wareham: Medical Research Council Epidemiology Unit, Elsie Widdowson Laboratory, University of Cambridge, Furnbourn Road, Cambridge CB1 9NL, United Kingdom.
Dr. Jukema: Department of Cardiology 5-P, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, the Netherlands.
Dr. Zwinderman: Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, Room J1B-226, 1100 DD Amsterdam, the Netherlands.
Author Contributions: Conception and design: S.M. Boekholdt, K. El-Harchaoui, M.S. Sandhu, R. Luben, K.T. Khaw.
Analysis and interpretation of the data: W.A. van der Steeg, S.M. Boekholdt, K. El-Harchaoui, J.W. Jukema, R. Luben, A.H. Zwinderman, J.J.P. Kastelein.
Drafting of the article: W.A. van der Steeg, S.M. Boekholdt, E.S.G. Stroes, J.J.P. Kastelein, K.T. Khaw.
Critical revision of the article for important intellectual content: W.A. van der Steeg, S.M. Boekholdt, E.A. Stein, K. El-Harchaoui, E.S.G. Stroes, M.S. Sandhu, J.W. Jukema, R. Luben, A.H. Zwinderman, K.T. Khaw, J.J.P. Kastelein.
Final approval of the article: W.A. van der Steeg, S.M. Boekholdt, E.S.G. Stroes, M.S. Sandhu, N.J. Wareham, J.W. Jukema, J.J.P. Kastelein, K.T. Khaw.
Provision of study materials or patients: M.S. Sandhu, N.J. Wareham, R. Luben, K.T. Khaw.
Statistical expertise: S.M. Boekholdt, M.S. Sandhu, A.H. Zwinderman.
Obtaining of funding: S.M. Boekholdt, N.J. Wareham, K.T. Khaw.
Administrative, technical, or logistic support: S.M. Boekholdt, J.W. Jukema, K.T. Khaw.
Collection and assembly of data: S.M. Boekholdt, E.A. Stein, N.J. Wareham, K.T. Khaw.
van der Steeg W., Boekholdt S., Stein E., El-Harchaoui K., Stroes E., Sandhu M., Wareham N., Jukema J., Luben R., Zwinderman A., Kastelein J., Khaw K.; Role of the Apolipoprotein B–Apolipoprotein A-I Ratio in Cardiovascular Risk Assessment: A Case–Control Analysis in EPIC-Norfolk. Ann Intern Med. 2007;146:640-648. doi: 10.7326/0003-4819-146-9-200705010-00007
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Published: Ann Intern Med. 2007;146(9):640-648.
Low-density lipoprotein (LDL) cholesterol is a primary treatment target in coronary artery disease (CAD) prevention guidelines (1), but it is a poor predictor of future cardiovascular events (2). Similarly, the ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol is a potent risk factor for CAD (3, 4), but it improves CAD risk prediction only modestly (5).
Apolipoprotein B and apolipoprotein A-I are the main structural proteins of atherogenic lipoproteins and HDL particles, respectively. In theory, the apolipoprotein B–apolipoprotein A-I (apo B–apo A-I) ratio could improve lipoprotein-related cardiovascular risk prediction. Apolipoprotein B levels reflect the entire spectrum of pro-atherogenic particles, including very-low-density, intermediate-density, and low-density lipoproteins, whereas LDL cholesterol levels do not (6). Apolipoprotein B levels also provide a good measure of the number of LDL particles, which reflects the atherogenicity of LDL (7, 8). In addition, apolipoprotein A-I is more important than HDL cholesterol content for biochemical pathways that make HDL antiatherogenic, including adenosine triphosphate binding cassette A1–mediated cellular cholesterol efflux (9), lecithin-cholesteryl acyltransferase–mediated maturation of HDL particles (10), and several antioxidative processes (11). Besides these physiologic considerations, apolipoprotein assessment does not require fasting blood samples (6), a feature that facilitates logistics at outpatient clinics. Collectively, these considerations have led to recommendations to implement the apo B–apo A-I ratio in routine clinical care (12).
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Cardiology, Dyslipidemia, Coronary Risk Factors, Prevention/Screening.
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