Cardiovascular disease is the leading cause of death in the Western world. Cardiovascular risk assessment includes tests for lipid and lipoprotein abnormalities, hypertension, and diabetes [1]; however, a need exists for more discriminating tests to detect risk in persons with near-normal to marginally elevated cholesterol and low-density lipoprotein (LDL) levels. Various factors can affect the atherogenic potential of cholesterol [1]. Oxidative modification of LDL plays an important role in the development of atherosclerosis [2]. Oxidatively modified LDL can influence atherogenesis through the recruitment of monocytes (chemotactic effect) and massive uptake of oxidatively modified LDL by scavenger receptors in the macrophage, leading to foam-cell formation. Epitopes of oxidatively modified LDL have been located in human atherosclerotic (but not normal) aortas, and antioxidants have been shown to markedly attenuate atherosclerosis.

If the oxidation of LDL is critical in atherogenesis, is it possible that a normal plasma LDL cholesterol level with enhanced oxidative stress can put one at a greater cardiovascular risk than does a mildly elevated plasma LDL cholesterol level with normal oxidative stress? Despite the interest in oxidatively modified LDL and the role of antioxidants, few studies have assessed the value of lipid peroxidation in predicting cardiovascular risk. Recently, tests for lipoprotein peroxidation potential have been developed using whole plasma [3] instead of isolated LDL [4], which can measure the total ability of a given plasma to resist metal-catalyzed peroxidation. Tests are available to detect the peroxidation products of both fatty acid (that is, malnaldehyde) and cholesterol (oxysterols). Finally, tests [5] to detect antibodies against oxidatively modified LDL showed a positive correlation with the progression of carotid atherosclerosis in humans. In summary, the introduction of lipid peroxidation tests in clinical and epidemiologic studies should be considered.