The Metabolic Syndrome, Circulating Oxidized LDL, and Risk of
The object of this study was to establish the association between the metabolic syndrome and oxidized LDL (oxLDL) and to determine the risk for coronary heart disease (CHD) in relation to the metabolic syndrome and levels of oxLDL. OxLDL was measured in plasma from 3,033 elderly participants in the Health, Aging, and Body Composition study. The metabolic syndrome was defined according to criteria established in the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. We observed that the metabolic syndrome was associated with higher levels of oxLDL due to a higher fraction of oxLDL, not to higher levels of LDL cholesterol. Individuals with the metabolic syndrome had twice the odds of having high oxLDL (>1.90 mg/dl) compared with those not having the metabolic syndrome, after adjusting for age, sex, ethnicity, smoking status, and LDL cholesterol. Among those participants who had the metabolic syndrome at study entry, incidence rates of future CHD events were 1.6-fold higher, after adjusting for age, sex, ethnicity, and smoking status. OxLDL was not an independent predictor of total CHD risk. However, those with high oxLDL showed a greater disposition to myocardial infarction (relative risk 2.25, 95% confidence interval 1.22-4.15). We concluded that the metabolic syndrome, a risk factor for CHD, is associated with higher levels of circulating oxLDL that are associated with a greater disposition to atherothrombotic coronary disease.

Oxidized LDL (oxLDL) has been shown to play an important role in the pathogenesis of atherosclerosis. We and others have demonstrated an association between cardiovascular disease (CVD) and oxidation of LDL. We have also found circulating oxLDL to be a prognostic marker of CVD in cardiac transplant patients. In middle-aged people, obesity and dyslipidemia are the strongest predictors of levels of oxLDL. Recently, the association between dyslipidemia and oxidation of LDL has been demonstrated in individuals in the pre-diabetic state. Finally, we have shown that in the Health, Aging, and Body Composition (Health ABC) cohort a high coronary heart disease (CHD) risk status (based on Framingham score) before CHD events is associated with high levels of circulating oxLDL, even after adjustment for LDL cholesterol.

Individuals with the metabolic syndrome are at increased risk for developing CHD as well as for mortality from CHD and other causes. The Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III) drew attention to the importance of the metabolic syndrome and provided a working definition of this syndrome. Findings from the Third National Health and Nutrition Examination Survey (NHANES III) showed that the metabolic syndrome is highly prevalent within the U.S.; that prevalence increased from 6.7% among participants ages 20-29 years to 43.5 and 42.0% for participants ages 60-69 years and ≥70 years, respectively.

Because the metabolic syndrome is associated with high risk for atherosclerotic disease, a process thought to involve LDL oxidation, we examined the relation between metabolic syndrome components and circulating oxLDL levels in the Health ABC cohort. Because we have found an association between the metabolic syndrome and higher prevalence of high levels of oxLDL, we sought to evaluate in a large-scale elderly population the potential relation among the metabolic syndrome, circulating oxLDL, and incident CHD events.