LDL Particle Size Distribution Is Associated With Carotid Intima-Media Thickness in Healthy 50-Year-Old Men

Abstract

Abstract-Results of cross-sectional and prospective studies have suggested that small, dense low-density lipoprotein (LDL) particles predispose to coronary heart disease. We investigated the relationships between plasma concentrations of LDL subfractions and intima-media thickness (IMT) of the common carotid artery (CCA), quantified by B-mode ultrasound, in 94 healthy, 50-year-old men, all of whom were homozygous for the apolipoprotein E3 allele. A novel 3% to 7.5% polyacrylamide gradient gel was developed to provide separation of LDL subfractions with high resolution, as was a procedure to quantify plasma concentrations of these LDL subspecies. The LDL particle size distribution pattern obtained by the gradient gel electrophoresis procedure was in good agreement with the one obtained by a well-established, single-spin density gradient ultracentrifugation technique. LDL-II (particle size, 23.5 to 25.0 nm) was the most abundant subfraction, and its plasma concentration correlated closely with the total LDL cholesterol concentration (rϭ0.61, PϽ0.001) but not with CCA IMT (rϭϪ0.13, NS). In contrast, the plasma concentration of the predominant small, dense LDL particle subfraction (LDL-III; particle size, 22.5 to 23.5 nm) correlated strongly with CCA IMT (rϭ0.42, PϽ0.001). In multivariate analysis, the plasma concentration of the LDL-III subfraction contributed significantly to the variation in CCA IMT (R 2 ϭ0.19). When plasma triglycerides and LDL cholesterol were forced into the multivariate model, 10% of the variation in CCA IMT was still accounted for by the LDL-III subfraction. In summary, use of a novel and sensitive gradient gel electrophoresis method for evaluation of LDL heterogeneity provided the basis for demonstrating an independent relation between the plasma concentration of small LDL and IMT of the CCA in healthy, middle-aged men. T he LDL fractions have been shown to be heterogeneous with regard to several structural and functional properties, such as size, 1-3 density, 3,4 electric charge, 5-7 and lipid and apolipoprotein composition. 5,8,9 Regarding potentially atherogenic properties, small, dense LDL species have been shown to be less resistant to oxidative modification 10 -12 and to bind more tightly to arterial wall proteoglycans 13,14 than larger and lighter LDL species. Both of these properties suggest an increased atherogenicity of small, dense LDL particles. Furthermore, small, dense LDL particles bind less efficiently to the LDL receptor 15,16 and hence have a prolonged residence time in plasma, giving them an extended opportunity to infiltrate the arterial wall, undergo oxidative modification, and exert atherogenic effects.Cross-sectional studies have consistently demonstrated the importance of LDL heterogeneity in coronary heart disease (CHD). [17][18][19][20][21] In addition, results of recent prospective studies indicate that a small LDL particle size predicts CHD. [22][23][24] However, the association between LDL particle size and CHD risk has been independent of the plasma triglyceri...

Low density lipoprotein size in relation to carotid intima-media thickness in coronary artery disease

“…In line with our results, LDL particle size has been reported to be associated with carotid IMT in middle-aged subjects in the study of Skoglund et al (30) and Hulthe et al (31,33).…”

“…The cross-sectional studies consistently suggest an association between small dense LDL particles and CAD. A plasma concentration of small dense LDL, (above 100 mg/dL) was associated with a 4.5-fold increased risk of CAD (30).…”

“…It has been demonstrated that small LDLs are independently related to common carotid artery IMT (30,32,34). In the study of Liu et al (24), LDL particle size correlated signifi cantly with mean IMT even after adjustment for age, BMI and sex.…”

The Metabolic Syndrome, LDL Particle Size, and Atherosclerosis

“…24 -28 A negative relationship between LDL particle size and IMT of the common carotid artery has recently been shown in subjects who are homozygous for the apoE3 allele. 29 However, in that study subjects with a high BMI (Ͼ32 kg/m 2 ) and plaque occurrence were excluded. The results are therefore not directly comparable to the results obtained in the present study.…”

“…A negative relationship between LDL particle size and intima-media thickness (IMT) has been found in a previous study by Skoglund-Andersson et al 29 In that study, only subjects homozygous for the apoE3 allele were included. Furthermore, subjects with a high body mass index (BMI Ͼ32 kg/m 2 ) and plaque occurrence were excluded.…”