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Role of the Apolipoprotein B–Apolipoprotein A-I Ratio in Cardiovascular Risk Assessment: A Case–Control Analysis in EPIC-Norfolk

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; and Kay-Tee Khaw, MBBChir
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From Academic Medical Center, Amsterdam, and Leiden University Medical Center, Leiden, the Netherlands; Metabolic & Atherosclerosis Research Center, Cincinnati, Ohio; and Medical Research Council Epidemiology Unit and Institute of Public Health, Cambridge, United Kingdom.

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, j.j.kastelein@amc.uva.nl.

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.

Ann Intern Med. 2007;146(9):640-648. doi:10.7326/0003-4819-146-9-200705010-00007
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Recent studies have shown that the apo B–apo A-I ratio is strongly associated with future CAD (2021). This association and the ability to measure apolipoprotein in nonfasting blood samples have led to recommendations that the apo B–apo A-I ratio be used in routine clinical care (12). The recommendation cannot be fully justified, however, until the apo B–apo A-I ratio is shown to be associated with CAD independent of traditional lipid variables and to be better at predicting future CAD events.

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Receiver-operating characteristic curves for the prediction of coronary artery disease.

Top. Results of models that included apolipoprotein B–apolipoprotein A-I (apo B–apo A-I) ratio or total cholesterol–high-density lipoprotein cholesterol (TC–HDL-C) ratio plus diabetes, body mass index, smoking, systolic blood pressure, and C-reactive protein level. Bottom. Results of models that used the Framingham risk score (FRS) alone or in combination with the apo B–apo A-I ratio. AUC = area under the curve.

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