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.
An elevated apolipoprotein B–apolipoprotein A-I (apo B–apo A-I) ratio is a risk factor for future coronary artery disease (CAD). It is not known whether this ratio is better than traditional lipid values for risk assessment and prediction and whether it adds predictive value to the Framingham risk score.
To evaluate whether the apo B–apo A-I ratio is associated with future CAD events independent of traditional lipid measurements and the Framingham risk score and to evaluate the ability of this ratio to predict occurrence of future CAD.
Prospective, nested case–control study.
Norfolk, United Kingdom.
Apparently healthy men and women (45 to 79 years of age) in the European Prospective Investigation into Cancer and Nutrition-Norfolk. Cases (n = 869) were persons who developed fatal or nonfatal CAD. Controls (n = 1511) were persons without CAD who were matched for age, sex, and enrollment period.
Total cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, apolipoprotein, and C-reactive protein levels were measured directly. Low-density lipoprotein (LDL) cholesterol values were calculated by using the Friedewald formula.
The apo B–apo A-I ratio was associated with future CAD events, independent of traditional lipid values (adjusted odds ratio, 1.85 [95% CI, 1.15 to 2.98]), including the total cholesterol–HDL cholesterol ratio, and independent of the Framingham risk score (adjusted odds ratio, 1.77 [CI, 1.31 to 2.39]). However, it did no better than lipid values at discriminating between CAD cases and controls (area under the receiver-operating characteristic curve, 0.670 for total cholesterol–HDL cholesterol ratio vs. 0.673 for apo B–apo A-I ratio [P = 0.38]) and added little to the predictive value of the Framingham risk score (area under the receiver-operating characteristic curve, 0.594 for Framingham risk score alone vs. 0.613 for Framingham risk score plus apo B–apo A-I ratio [P < 0.001]). In addition, it incorrectly classified 41.1% of cases and 50.4% of controls.
No participant was taking lipid-lowering medication, and diabetes was uncommon.
The apo B–apo A-I ratio is independently associated with, but adds little to, existing measures for CAD risk assessment and discrimination in the general population. Other characteristics of the test, such as the ability to perform it on nonfasting samples, may still make it useful in some settings.
Wim A. van der Steeg, S. Matthijs Boekholdt, Evan A. Stein, Karim El-Harchaoui, Erik S.G. Stroes, Manjinder S. Sandhu, et al. 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.
Cardiology, Coronary Risk Factors, Dyslipidemia, Prevention/Screening.
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