Advanced Lipoprotein Testing Does Not Improve Identification of Subclinical Atherosclerosis in Young Adults: The Bogalusa Heart Study

3 May 2005 | Volume 142 Issue 9 | Pages 742-750

Background: The clinical value of advanced lipoprotein testing relative to traditional lipid testing remains controversial. To date, no studies have evaluated associations between advanced lipoprotein testing and subclinical atherosclerosis in healthy young adults.

Objective: To determine whether advanced lipoprotein testing using vertical-spin density-gradient ultracentrifugation better predicts carotid intima-media thickness, a validated measure of subclinical atherosclerosis, than does traditional lipoprotein testing in asymptomatic young adults.

Design: Cross-sectional community-based study.

Setting: Bogalusa, Louisiana.

Participants: 311 randomly selected adults from the Bogalusa Heart Study who were 20 to 38 years of age.

Measurements: The authors performed advanced lipoprotein testing using vertical-spin density-gradient ultracentrifugation, traditional testing using enzymatic methods, and Friedewald formula estimation of low-density lipoprotein cholesterol levels. A certified reader blinded to lipoprotein results determined carotid intima-media thickness by B-mode ultrasonography. C-statistics from area under the receiver-operating characteristic curves (AUCs) derived from multivariable regression models were compared.

Results: Lipid values obtained with advanced lipoprotein testing did not predict carotid intima-media thickness better than traditionally measured lipid values in 236 participants for whom all data were available. A model using traditional lipoprotein measures (AUC, 0.754 [95% CI, 0.690 to 0.812]) did not differ significantly from a model using advanced lipoprotein measures (AUC, 0.779 [CI, 0.662 to 0.871]) for prediction of carotid intima-media thickness (P > 0.2). Subclass pattern of LDL, lipoprotein(a) cholesterol, intermediate-density lipoprotein cholesterol, high-density lipoprotein cholesterol subclasses, and very-low-density lipoprotein subclasses did not improve the performance of models for prediction of carotid intima-media thickness.

Limitations: The study was cross-sectional, cardiac events were not determined, and only 1 method of advanced lipoprotein testing was used.

Conclusions: Advanced lipoprotein testing using vertical-spin density-gradient ultracentrifugation did not improve prediction of carotid intima-media thickness in young adults and may not be useful for assessing cardiovascular risk in this population.

Editors' Notes Context Traditional lipoprotein testing methods do not directly measure low-density lipoprotein cholesterol, lipoprotein(a), lipid remnants, or particle size. Does measurement of these laboratory values improve prediction of atherosclerosis? Contribution This cross-sectional study of 311 healthy young adults used vertical-spin density-gradient ultracentrifugation to directly measure multiple lipoprotein subclass patterns, lipoprotein(a), and intermediate-density lipoprotein cholesterol. These values did not predict carotid intima-media thickness better than traditionally measured lipid values. Cautions Carotid intima-media thickness is an imperfect measure of clinically important atherosclerosis. Associations between lipoproteins and carotid intima-media thickness may differ between healthy people and older people with known atherosclerosis. –The Editors

 

Author and Article Information

From University of Wisconsin Medical School, Madison, Wisconsin; Duke University Medical Center, Durham, North Carolina; and Tulane University Health Sciences Center, New Orleans, Louisiana.

Acknowledgment: The authors thank the participants in the Bogalusa Heart Study.

Grant Support: By the National Center for Research Resources (RR-1617601); the National Heart, Lung, and Blood Institute (HL-07936 and HL-38844); the National Institute on Aging (AG-16592); the National Institute of Child Health and Human Development (HD-043820); and the American Heart Association (0160261B).

Potential Financial Conflicts of Interest: Consultancies: J.H. Stein (LipoScience Inc.); Honoraria: J.H. Stein (LipoScience Inc.); Grants received: W.S. Tzou (National Heart, Lung, and Blood Institute, National Institutes of Health); S.R. Srinivasan (National Institute of Child Health and Human Development, National Institutes of Health), W. Chen (National Institute of Child Health and Human Development, National Institutes of Health), G. Berenson (National Heart, Lung, and Blood Institute, National Institute on Aging, National Institutes of Health), J.H. Stein (National Center for Research Resources, National Institutes of Health); Grants pending: G. Berenson (National Heart, Lung, and Blood Institute, National Institutes of Health).

Requests for Single Reprints: James H. Stein, MD, Department of Medicine, Section of Cardiovascular Medicine, University of Wisconsin Medical School, 600 Highland Avenue, G7/341 CSC (MC 3248), Madison, WI 53792.

Current Author Addresses: Dr. Tzou: Department of Medicine, Section of Cardiovascular Medicine, University of Wisconsin Medical School, 600 Highland Avenue, H6/349 CSC (MC 3248), Madison, WI 53792.

Dr. Douglas: Division of Cardiovascular Medicine, Duke University, Duke University Medical Center 3943, Duke North 7451A, Erwin Road, Durham, NC 27710.

Drs. Srinivasan, Chen, and Berenson: Tulane Center for Cardiovascular Health and Department of Epidemiology, Tulane University Health Sciences Center, 1430 Tulane Avenue SL 18, New Orleans, LA 70112-2699.

Dr. Stein: Department of Medicine, Section of Cardiovascular Medicine, University of Wisconsin Medical School, 600 Highland Avenue, G7/341 CSC (MC 3248), Madison, WI 53792.

Author Contributions: Conception and design: P.S. Douglas, S.R. Srinivasan, W. Chen, G. Berenson, J.H. Stein.

Analysis and interpretation of the data: W.S. Tzou, J.H. Stein.

Drafting of the article: W.S. Tzou.

Critical revision of the article for important intellectual content: W.S. Tzou, P.S. Douglas, G. Berenson, J.H. Stein.

Final approval of the article: P.S. Douglas, S.R. Srinivasan, W. Chen, G. Berenson.

Obtaining of funding: S.R. Srinivasan, W. Chen, G. Berenson, J.H. Stein.

Administrative, technical, or logistic support: P.S. Douglas, S.R. Srinivasan, G. Berenson, J.H. Stein.

Collection and assembly of data: S.R. Srinivasan, W. Chen.

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Response to Letter to the Editor

James H. Stein, et al.

Annals Online, 15 Jun 2005 [Full text]