Association between carotid intima-media thickness and low-density lipoprotein size and susceptibility of low-density lipoprotein to oxidation in asymptomatic members of familial combined hyperlipidemia families

Background and Purpose-In addition to low-density lipoprotein (LDL) cholesterol, small, dense LDL particles and oxidative modification of LDL have been linked to the pathogenesis of atherosclerosis. The present study was aimed at investigating the association between carotid artery intima-media thickness (IMT) and LDL particle size and susceptibility of LDL to oxidation in vitro in asymptomatic members of familial combined hyperlipidemia (FCHL) families. Methods-LDL particle size. susceptibility of LDL to oxidation in vitro, and carotid IMT were measured in 148 asymptomatic FCHL family members. Results-LDL particle size and lag time for LDL oxidation were reduced in hyperlipidemic compared with normolipidemic family members. LDL particle size. serum total cholesterol, and a-tocopherol in LDL were independently associated with lag time for LDL oxidation in multivariate analysis. LDL particle size A as associated with carotid mean IMT independently of clinical, lipid. and antioxidant variables in multivariate analysis. Although the susceptibility of LDL to oxidation in vitro was correlated with mean IMT. it did not have a significant independent contribution to variation in mean IMT in the multivariate model. Conclusions-We conclude that LDL particle size but not susceptibility of LDL to oxidation in vitro is independently associated with carotid IMT in asymptomatic FCHL family members. These results imply that small, dense LDL as an inherent feature of FCHL is an important diagnostic indicator for coronary artery disease risk in FCHL.