Oxidized LDL and coronary heart disease

Abstract

During inflammation, several cell types synthesize and secrete phospholipase A2 that catalyses lipid oxidation in LDL. Myeloperoxidase, a haeme protein secreted by activated phagocytes, oxidizes L-tyrosine to a tyrosyl radical that is a physiological catalyst for the initiation of lipid oxidation in LDL. Lipid oxidation results in the generation of aldehydes that substitute lysine residues in the apolipoprotein B-100 moiety. Lipid together with protein oxidation in LDL results in the generation of oxidized LDL.

We, among others, have demonstrated an association between coronary heart disease (CHD) and increased plasma levels of oxidized LDL. Recently, we have demonstrated a higher prevalence of elevated oxidized LDL in persons with high-calculated CHD risk prior to events. The odds of having elevated oxidized LDL for persons with high-calculated CHD risk prior to events were even higher than for persons with diagnosed CHD. A likely explanation is that once CHD has been diagnosed the patients are more treated with a statin that appears to decrease oxidized LDL even beyond its cholesterol-lowering effect.We have identified several metabolic syndrome components (high triglycerides, low HDL-cholesterol, glucose intolerance and diabetes) that independently of LDLcholesterol, predicted high levels of oxidized LDL.

Finally, elevated oxidized LDL predicted myocardial infarction in the Health ABC cohort consisting of well-functioning elderly people, even after adjusting for age, gender, race, smoking, and the metabolic syndrome.

Key Words:

• oxidized LDL
• metabolic syndrome
• cardiovascular risk
• elderly
• epidemiology
• atherosclerosis