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Paul Holvoet, PhD; Duk-Hee Lee, MD, PhD; Michael Steffes, MD, PhD; Myron Gross, PhD; David R. Jacobs Jr, PhD

JAMA. 2008;299(19):2287-2293.

Context  Experimental data support the hypothesis that oxidized low-density lipoprotein (LDL) is associated with the metabolic syndrome. However, this hypothesis has not been tested in humans.

Objective  To establish the relation of oxidized LDL with metabolic syndrome in the general community.

Design, Setting, and Participants  The Coronary Artery Risk Development in Young Adults (CARDIA) study is a population-based, prospective, observational study. We studied 1889 participants who were between the ages of 18 and 30 years at the time of recruitment in 1985 and 1986 and living in 1 of 4 US metropolitan areas (41% African American; 56% women) and were seen both at year 15 (2000-2001, ages 33-45 years) and year 20 examinations (2005-2006).

Main Outcome Measure  The longitudinal association of oxidized LDL and incident metabolic syndrome. Oxidized LDL was measured with a monoclonal antibody-based enzyme-linked immunosorbent assay. The metabolic syndrome was defined according to the Adult Treatment Panel III of the National Cholesterol Education Program.

Results  Incident metabolic syndrome was diagnosed at the year 20 follow-up in 12.9% (243 of 1889) of participants who did not have metabolic syndrome at the 15-year follow-up. The odds ratios (ORs) for incident metabolic syndrome after 5 years' follow-up and adjusted for age, sex, race, study center, cigarette smoking, body mass index, physical activity, and LDL cholesterol levels by quintiles of oxidized LDL were 2.1 (95% confidence interval [CI], 1.1-3.8) for the second quintile (55.4-69.1 U/L); 2.4 (95% CI, 1.3-4.3) for the third quintile (69.2-81.2 U/L); 2.8 (95% CI, 1.5-5.1) for the fourth quintile (81.3-97.3 U/L); and 3.5 (95% CI, 1.9-6.6) for the fifth quintile (97.4 U/L). The adjusted ORs for incidence of dichotomous components of metabolic syndrome in the highest vs the lowest quintile of oxidized LDL were 2.1 (95% CI, 1.2-3.6) for abdominal obesity, 2.4 (95% CI, 1.5-3.8) for high fasting glucose, and 2.1 (95% CI, 1.1-4.0) for high triglycerides. Low-density lipoprotein cholesterol was not associated with incident metabolic syndrome or with any of its components in the fully adjusted model containing oxidized LDL.

Conclusion  Higher concentration of oxidized LDL was associated with increased incidence of metabolic syndrome overall, as well as its components of abdominal obesity, hyperglycemia, and hypertriglyceridemia.

Author Affiliations: Atherosclerosis and Metabolism Unit, Katholieke Universiteit Leuven, Belgium (Dr Holvoet); Division of Epidemiology and Community Health, School of Public Health (Drs Lee and Jacobs) and Department of Laboratory Medicine and Pathology (Drs Gross and Steffes), University of Minnesota, Minneapolis; Department of Preventive Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea (Dr Lee); and Department of Nutrition, University of Oslo, Oslo, Norway (Dr Jacobs).

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