Increased circulating malondialdehyde-modified LDL levels in patients with coronary artery diseases and their association with peak sizes of LDL particles.

Abstract

Recent establishment of a sensitive ELISA system using antibodies against malondialdehyde-modified low density lipoprotein (MDA-LDL) made it possible to determine the circulating oxidized lipoprotein levels. Here, we investigated the serum levels of MDA-LDL in 62 patients with coronary artery disease (CAD) compared with the levels in 42 patients without CAD [groups CAD(+) and CAD(-), respectively], which are adjusted for age, serum total cholesterol, LDL and high density lipoprotein cholesterol, and triglyceride levels. Serum MDA-LDL levels were 113.4+/-49.1 IU/L in CAD(+), which were significantly higher than the levels in CAD(-) (85.2+/-22.5 IU/L, P<0.0005). The ratio of MDA-LDL/LDL cholesterol was 0.95+/-0.32 in CAD(+), indicating a significant increase compared with the ratio in CAD(-) (0.68+/-0.19, P<0.0005). The positive correlation of MDA-LDL level and the ratio of MDA-LDL/LDL cholesterol with intima-media thickness in carotid arteries was observed. Age was not clearly associated with the MDA-LDL level (P=0.865). The serum MDA level was positively correlated with LDL cholesterol (P<0.0001) and with triglycerides (P<0.001) and negatively correlated with high density lipoprotein cholesterol (P<0.05). Furthermore, the MDA-LDL level was negatively correlated with the peak size of the LDL particle (P<0.01). The LDL subclasses that were identified by using the sera collected from the subjects by sequential ultracentrifugation showed that the ratios of MDA-LDL/apolipoprotein B in LDL3 and LDL4 were nearly 3-fold higher than those in LDL1 and LDL2 for CAD(+) and CAD(-). These results indicate that the circulating MDA-LDL level is increased in CAD(+), independent of the serum LDL cholesterol level but in association with the peak size of LDL particles. The measurement of serum MDA-LDL level may be useful for the identification of patients with advanced atherosclerosis.