Circulating oxidized low-density lipoprotein and its association with carotid intima-media thickness in asymptomatic members of familial combined hyperlipidemia families.
OBJECTIVE
Oxidized low-density lipoprotein (Ox-LDL)is implicated in the pathogenesis of atherosclerosis. Circulating oxidation-specific epitopes on plasma Ox-LDL has been linked with coronary artery disease, but its determinants and its association with early development of atherosclerosis in familial combined hyperlipidemia (FCHL) has not been very well studied. This study aimed to investigate the determinants of the circulating Ox-LDL and the association between Ox-LDL and carotid intima-media thickness (IMT) in asymptomatic members of FCHL families.


RESULTS
Ox-LDL, susceptibility of LDL to oxidation in vitro, plasma 8-isoprostane and antioxidants, lipids and lipoproteins, LDL particle size, and carotid IMT were measured in 150 asymptomatic FCHL family members. Affected FCHL family members had reduced LDL particle size and lag time for LDL oxidation, increased plasma levels of Ox-LDL, increased plasma urate and alpha-tocopherol, and a trend for the increase of 8-isoprostane as compared with nonaffected FCHL. Ox-LDL was independently associated with serum LDL cholesterol, apoB, and 8-isoprostane in multivariate analysis but only univariately correlated with LDL particle size and lag time for LDL oxidation. In addition, Ox-LDL was significantly associated with carotid mean IMT independently of other clinical and biochemical variables in a multivariate model.


CONCLUSIONS
Serum LDL cholesterol, apoB levels, and 8-isoprostane were the most important determinants of Ox-LDL. Ox-LDL is independently associated with carotid IMT in asymptomatic FCHL family members and can be used as a marker of early atherosclerosis in FCHL.
Liu
Ming-Lin
ML
Department of Medicine, Helsinki University Central Hospital, University of Helsinki, Finland.
Ylitalo
Kati
K
Salonen
Riitta
R
Salonen
Jukka T
JT
Taskinen
Marja-Riitta
MR
D000328:Adult; D000975:Antioxidants / Q000032:analysis; D015415:Biomarkers; D002339:Carotid Arteries / Q000000981:diagnostic imaging* / Q000648:ultrastructure; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000209:etiology; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000097:blood; D004198:Disease Susceptibility; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood* / Q000235:genetics / Q000473:pathology; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood* / Q000737:chemistry; D008297:Male; D010316:Particle Size; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000648:ultrastructure; D017540:Tunica Media / Q000000981:diagnostic imaging / Q000648:ultrastructure; D014463:Ultrasonography
D000975:Antioxidants; D015415:Biomarkers; D008055:Lipids; D008074:Lipoproteins; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost