In search of biological markers of high-risk carotid artery atherosclerotic plaque: Enhanced LDL oxidation

The oxidation of low density lipoprotein (LDL) is a key event in the development and progression of atherosclerosis because it generates molecular epitopes that are more atherogenic than parent LDL. We found previously that patients with carotid atherosclerosis have a significantly higher titer of autoantibodies against oxidatively modified LDL than normal subjects. The aim of this study is to correlate biological markers of in vivo LDL oxidation with the degree of carotid stenosis and of plaque ulceration (PU) in a series of patients undergoing carotid endoarteriectomy (CEA). Ninety-four consecutive patients (68M and 26F, aged 67.3 +/- 8.2 years) who underwent CEA at our institution between June 1993 and January 1994 were included in the study. The degree of carotid stenosis and the presence and extent of PU were correlated with the level of autoantibodies (IgG) against oxidatively modified LDL (Cu++-oxidized [oxLDL] or malondialdehyde derivatized LDL [MDA-LDL]), that consistently mirrors the occurrence of oxidative modifications in vivo. A statistically significant correlation (r = 0.23, p = 0.039) was found between the degree of carotid stenosis and antiMDA-LDL specific ratio (a parameter that describes the specificity of LDL towards other proteins as target for oxidative modification). A statistically significant correlation was also found between the PU score and antioxLDL IgG (r = 0.32, p = 0.011), antiMDA-LDL IgG (r = 0.25, p = 0.045) and antiMDA-LDL IgG specific ratio (r = 0.38, p = 0.002). None of the classical biochemical parameters (total, LDL and HDL cholesterol and triglycerides) correlated with the above-mentioned plaque characteristics. The results shown, support the use of biological markers of in vivo LDL oxidation (antioxidatively modified LDL autoantibody titers) to evaluate the clinical setting of high-risk carotid atherosclerosis both in screening and in follow-up studies.