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Plasma F₂-Isoprostanes and Coronary Artery Calcification: The CARDIA Study

¹ Department of Laboratory Medicine and Pathology, School of Medicine, and ² Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis, MN.
³ Division of Preventive Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL.
⁴ National Heart, Lung, and Blood Institute, Division of Epidemiology and Clinical Applications, Bethesda, MD.
⁵ The Department of Nutrition, University of Oslo, Oslo, Norway.

^aAddress correspondence to this author at: Department of Laboratory Medicine and Pathology, School of Medicine, University of Minnesota, Mayo Mail Code 609, 420 Delaware Street Southeast, Minneapolis, MN 55455. 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, mean (SD), 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.

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