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Received on June 1, 2004
Accepted on October 12, 2004
Lipids, Lipoproteins, and Cardiovascular Risk Factors |
1 Department of Laboratory Medicine and Pathology, School of Medicine, School of Public Health, University of Minnesota, Minneapolis, MN
2 Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis, MN, and The Institute for Nutrition Research, University of Oslo, Oslo, Norway
3 Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis, MN
4 Division of Preventive Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL
5 National Heart, Lung, and Blood Institute, Division of Epidemiology and Clinical Applications, Bethesda, MD
* To whom correspondence should be addressed. E-mail: gross{at}epi.umn.edu.
Background: Oxidation of lipids in lipoproteins and cells may initiate and enhance the early development of cardiovascular disease.
Method and Results: We assayed F2-isoprostanes, oxidation products of arachidonic acid, by gas chromatography/mass spectrometry in a biracial cohort of 2850 young healthy adult men and women. Coronary artery calcification (CAC), a component of coronary artery atherosclerosis, was detectable in 10% of the cohort and appeared to be in its initial stages (Agatston scores <20 in 47% and <100 in 83% of CAC-positive participants). After adjusting for sex, clinical site, age, and race, the presence of any CAC was 24% more likely among those with high vs low concentrations of F2-isoprostanes [odds ratio (OR) = 1.24 per 92.2 pmol/L (32.7 ng/L; 1 SD of F2-isoprostanes); 95% confidence interval (CI), 1.09-1.41]. The OR was only slightly attenuated [1.18 per 92.2 pmol/L (32.7 ng/L); CI, 1.02-1.38] after further adjustment for body mass index, smoking, serum lipids, C-reactive protein, antioxidant supplementation use, diabetes, and blood pressure. As a continuous variable, the Agatston score increased by 6.9% per 92.2 pmol/L (32.7 ng/L) of F2-isoprostane concentration (P <0.01). Whereas CAC prevalence was lower in women than men, F2-isoprostanes were higher in women {190 (108.9) pmol/L [67.4 (38.6) ng/L]} than in men {140.4 (55.6) pmol/L [49.8 (19.7) ng/L]}. Nevertheless, F2-isoprostanes were associated with an increased risk of CAC in both sexes.
Conclusion: This association between increased concentrations of circulating F2-isoprostanes and CAC in young healthy adults supports the hypothesis that oxidative damage is involved in the early development of atherosclerosis.
The following articles in journals at HighWire Press have cited this article:
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  B. Thyagarajan, D. R. Jacobs Jr., J. J. Carr, O. Alozie, M. W. Steffes, P. Kailash, J. H. Hayes, and M. D. Gross Factors Associated with Paraoxonase Genotypes and Activity in a Diverse, Young, Healthy Population: The Coronary Artery Risk Development in Young Adults (CARDIA) Study Clin. Chem., April 1, 2008; 54(4): 738 - 746. [Abstract] [Full Text] [PDF]
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 T. S. Perlstein, R. L. Pande, J. A. Beckman, and M. A. Creager Serum Total Bilirubin Level and Prevalent Lower-Extremity Peripheral Arterial Disease: National Health and Nutrition Examination Survey (NHANES) 1999 to 2004 Arterioscler. Thromb. Vasc. Biol., January 1, 2008; 28(1): 166 - 172. [Abstract] [Full Text] [PDF]
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 T. Wu, N. Rifai, W. C. Willett, and E. B. Rimm Plasma Fluorescent Oxidation Products: Independent Predictors of Coronary Heart Disease in Men Am. J. Epidemiol., September 1, 2007; 166(5): 544 - 551. [Abstract] [Full Text] [PDF]
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 C.-D. Lee, D. R Jacobs Jr, P. J Schreiner, C. Iribarren, and A. Hankinson Abdominal obesity and coronary artery calcification in young adults: the Coronary Artery Risk Development in Young Adults (CARDIA) Study Am. J. Clinical Nutrition, July 1, 2007; 86(1): 48 - 54. [Abstract] [Full Text] [PDF]
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A. Hozawa, D. R. Jacobs Jr., M. W. Steffes, M. D. Gross, L. M. Steffen, and D.-H. Lee Relationships of Circulating Carotenoid Concentrations with Several Markers of Inflammation, Oxidative Stress, and Endothelial Dysfunction: The Coronary Artery Risk Development in Young Adults (CARDIA)/Young Adult Longitudinal Trends in Antioxidants (YALTA) Study Clin. Chem., March 1, 2007; 53(3): 447 - 455. [Abstract] [Full Text] [PDF]
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Y. Hu, G. Block, E. P Norkus, J. D Morrow, M. Dietrich, and M. Hudes Relations of glycemic index and glycemic load with plasma oxidative stress markers Am. J. Clinical Nutrition, July 1, 2006; 84(1): 70 - 76. [Abstract] [Full Text] [PDF]
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X. Yu, D. R. Jacobs Jr, P. J. Schreiner, M. D. Gross, M. W. Steffes, and M. Fornage The Uncoupling Protein 2 Ala55Val Polymorphism Is Associated with Diabetes Mellitus: The CARDIA Study Clin. Chem., August 1, 2005; 51(8): 1451 - 1456. [Abstract] [Full Text] [PDF]
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I. S. Young Oxidative Stress and Vascular Disease: Insights from Isoprostane Measurement Clin. Chem., January 1, 2005; 51(1): 14 - 15. [Full Text] [PDF]
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