Leuven, Belgium - A 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 in a new population-based study [1].

The study, published in the May 21, 2008 issue of the Journal of the American Medical Association, was conducted by a team led by Dr Paul Holvoet (Katholieke Universiteit Leuven, Belgium).

Senior author Dr David Jacobs (University of Minnesota, Minneapolis) commented to heartwire: "This is another piece of evidence suggesting that oxidized LDL is harmful and is a signal of future heart disease risk even in people who are currently young and healthy."

The authors explain that studies in cellular and animal models have suggested that oxidized LDL, which accounts for only a minor fraction of LDL (0.001%-5%), contributes to processes that lead to the incidence of the metabolic syndrome, but this association has not been tested in humans.

They therefore set out to determine the association between the concentration of oxidized LDL and the incidence five years later of metabolic syndrome and its components in the population-based Coronary Artery Risk Development in Young Adults (CARDIA) study.

The CARDIA study followed 5115 participants who were between the ages of 18 and 30 years at the time of recruitment in 1985-1986 from four US metropolitan areas for 20 years. Oxidized LDL was assessed in 2823 participants at year 15 (2000-2001) as part of the Young Adult Longitudinal Trends in Antioxidants (YALTA) ancillary study. After the exclusion of participants who were pregnant, did not fast for at least eight hours before the test, had missing data, or who already had metabolic syndrome, the remaining 1889 patients were included in this study.

Results from the 20-year examination showed that 243 (12.9%) of these 1889 participants had developed metabolic syndrome. After adjustment for many different variables, oxidized LDL showed a graded relation to incident metabolic syndrome, with those in the highest quintile of oxidized LDL having a 3.5-times increased risk of metabolic syndrome compared with those in the lowest.

High levels of oxidized LDL were also associated with three of the individual components of metabolic syndrome—obesity, hypertriglyceridemia, and high fasting glucose—but were not associated with raised blood pressure or HDL cholesterol.

These associations remained significant after adjustment for CRP, adiponectin, and antihypertensive, antidiabetic, and cholesterol-lowering medication.

In contrast, LDL cholesterol showed only a limited relation with metabolic syndrome, which the authors note tended to become flat in the fully adjusted model including oxidized LDL.

They conclude: "As yet, it is not possible to conclude whether oxidized LDL is a marker related to mechanistic underlying factors on the pathway to the development of metabolic syndrome or whether it is by itself a functional intermediary in this pathway. However, the strong association of oxidized LDL with the incidence of metabolic syndrome is consistent with a causal role."