This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Skoglund-Andersson, C. Articles by Karpe, F. Search for Related Content PubMed PubMed Citation Articles by Skoglund-Andersson, C. Articles by Karpe, F. Related Collections Lipids Lipid and lipoprotein metabolism Pathophysiology Risk Factors

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:2422-2430.)
© 1999 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

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

Camilla Skoglund-Andersson; Rong Tang; M. Gene Bond; Ulf de Faire; Anders Hamsten; Fredrik Karpe

From the Atherosclerosis Research Unit, King Gustaf V Research Institute (C.S.-A., A.H., F.K.), and the Department of Emergency and Cardiovascular Medicine (U.d.F., A.H., F.K.), Karolinska Hospital, and Institute of Environmental Medicine, Division of Cardiovascular Epidemiology, Karolinska Institute (U.d.F.), Stockholm, Sweden; and Center for Medical Ultrasound, Division of Vascular Ultrasound Research, Wake Forest University School of Medicine, Winston-Salem, NC (R.T., M.G.B.).

Correspondence to Camilla Skoglund-Andersson, King Gustaf V Research Institute, Karolinska Hospital, S-171 76 Stockholm, Sweden. E-mail camilla{at}instmed.ks.se

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 (r=0.61, P<0.001) but not with CCA IMT (r=-0.13, 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 (r=0.42, P<0.001). In multivariate analysis, the plasma concentration of the LDL-III subfraction contributed significantly to the variation in CCA IMT (R²=0.19). 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.

Key Words: intima-media thickness • atherosclerosis • low-density lipoprotein subfractions • gradient gel electrophoresis • apolipoprotein B

This article has been cited by other articles:

				S. Shrestha, H. C. Freake, M. M. McGrane, J. S. Volek, and M. L. Fernandez A Combination of Psyllium and Plant Sterols Alters Lipoprotein Metabolism in Hypercholesterolemic Subjects by Modifying the Intravascular Processing of Lipoproteins and Increasing LDL Uptake J. Nutr., May 1, 2007; 137(5): 1165 - 1170. [Abstract] [Full Text] [PDF]

				B. Lundahl, C. Skoglund-Andersson, M. Caslake, D. Bedford, P. Stewart, A. Hamsten, C. J. Packard, and F. Karpe Microsomal triglyceride transfer protein -493T variant reduces IDL plus LDL apoB production and the plasma concentration of large LDL particles Am J Physiol Endocrinol Metab, April 1, 2006; 290(4): E739 - E745. [Abstract] [Full Text] [PDF]

				M. Rizzo and K. Berneis Low-density lipoprotein size and cardiovascular risk assessment QJM, January 1, 2006; 99(1): 1 - 14. [Abstract] [Full Text] [PDF]

				P. Sjogren, M. Rosell, C. Skoglund-Andersson, S. Zdravkovic, B. Vessby, U. de Faire, A. Hamsten, M.-L. Hellenius, and R. M. Fisher Milk-Derived Fatty Acids Are Associated with a More Favorable LDL Particle Size Distribution in Healthy Men J. Nutr., July 1, 2004; 134(7): 1729 - 1735. [Abstract] [Full Text]

				D. S. Freedman, J. D. Otvos, E. J. Jeyarajah, I. Shalaurova, L. A. Cupples, H. Parise, R. B. D'Agostino, P. W.F. Wilson, and E. J. Schaefer Sex and Age Differences in Lipoprotein Subclasses Measured by Nuclear Magnetic Resonance Spectroscopy: The Framingham Study Clin. Chem., July 1, 2004; 50(7): 1189 - 1200. [Abstract] [Full Text] [PDF]

				R. Carmena, P. Duriez, and J.-C. Fruchart Atherogenic Lipoprotein Particles in Atherosclerosis Circulation, June 15, 2004; 109(23_suppl_1): III-2 - III-7. [Abstract] [Full Text]

				J. E Macioch, C D. Katsamakis, J. Robin, P. R Liebson, P. M Meyer, C. Geohas, J. S Raichlen, M. H Davidson, and S. B Feinstein Effect of contrast enhancement on measurement of carotid artery intimal medial thickness Vascular Medicine, February 1, 2004; 9(1): 7 - 12. [Abstract] [PDF]

				F. M. Sacks and H. Campos Low-Density Lipoprotein Size and Cardiovascular Disease: A Reappraisal J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4525 - 4532. [Full Text] [PDF]

				E. Faggin, A. Zambon, M. Puato, S. S. Deeb, S. Bertocco, S. Sartore, G. Crepaldi, A. C. Pessina, and P. Pauletto Association between the -514 c->t polymorphism of the hepatic lipase gene promoter and unstable carotid plaque in patients with severe carotid artery stenosis J. Am. Coll. Cardiol., September 18, 2002; 40(6): 1059 - 1066. [Abstract] [Full Text] [PDF]

				F. M. Yatsu and J. D. Morrisett Carotid Intima-Media Thickness in Familial Combined Hyperlipidemia and LDL Size Stroke, May 1, 2002; 33(5): 1174 - 1175. [Full Text] [PDF]

				M.-L. Liu, K. Ylitalo, I. Nuotio, R. Salonen, J. T. Salonen, and M.-R. Taskinen 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 Stroke, May 1, 2002; 33(5): 1255 - 1260. [Abstract] [Full Text] [PDF]

				T. Skoog, W. Dichtl, S. Boquist, C. Skoglund-Andersson, F. Karpe, R. Tang, M.G. Bond, U. de Faire, J. Nilsson, P. Eriksson, et al. Plasma tumour necrosis factor-{alpha} and early carotid atherosclerosis in healthy middle-aged men Eur. Heart J., March 1, 2002; 23(5): 376 - 383. [Abstract] [Full Text] [PDF]

				E. T.P. Keulen, M. Kruijshoop, N. C. Schaper, A. P.G. Hoeks, and T. W.A. de Bruin Increased Intima-Media Thickness in Familial Combined Hyperlipidemia Associated With Apolipoprotein B Arterioscler. Thromb. Vasc. Biol., February 1, 2002; 22(2): 283 - 288. [Abstract] [Full Text] [PDF]

				B. Lundahl, A. Hamsten, and F. Karpe Postprandial Plasma ApoB-48 Levels Are Influenced by a Polymorphism in the Promoter of the Microsomal Triglyceride Transfer Protein Gene Arterioscler. Thromb. Vasc. Biol., February 1, 2002; 22(2): 289 - 293. [Abstract] [Full Text] [PDF]

				J. Hulthe, L. Bokemark, J. Wikstrand, and B. Fagerberg The Metabolic Syndrome, LDL Particle Size, and Atherosclerosis : The Atherosclerosis and Insulin Resistance (AIR) Study Arterioscler. Thromb. Vasc. Biol., September 1, 2000; 20(9): 2140 - 2147. [Abstract] [Full Text] [PDF]