Advertisement

LDL particle size in subjects with previously unsuspected coronary heart disease: relationship with other cardiovascular risk markers

      Abstract

      Low density lipoprotein (LDL) particle diameters were determined by non-denaturing gradient gel electrophoresis in 53 subjects with previously unrecognised coronary heart disease (CHD) and 167 control subjects matched by age, sex and total plasma cholesterol. The mean diameter of the major LDL peak was found not to be significantly different between the two groups, but the CHD subjects were found to have a broader distribution of the predominant LDL species ((25.0 (24.7–25.3)nm versus 24.8 (24.7–24.9)nm)) (median (25–75%)), a greater proportion of larger particles (χ2 = 19.8, P < 0.001) and to be more likely to have multiple numbers of LDL species than the control subjects (χ2 = 22.7, P < 0.001). A negative correlation was found between the diameter of the predominant LDL species and fasting plasma triglyceride (r = −0.21, P = 0.0015), waist to hip ratio (WHR) (r = −0.15, P = 0.026) and body mass index (BMI) (r = −0.20, P = 0.002), and in a subgroup of subjects (n = 106), postprandial analysis revealed a negative correlation with the incremental postprandial response of plasma insulin (r = −0.19, P = 0.025). Male subjects had a significantly smaller diameter of the major LDL peak (24.8 ± 0.0 nm) than female subjects (25.0 ± 0.0 nm, P < 0.001). The present study failed to confirm an association between small LDL particles and the presence of coronary heart disease but did demonstrate more LDL heterogeneity in those with CHD. In addition, significant relationships were evident between the diameter of the major LDL peak and a number of other risk factors for coronary disease.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Austin MA
        • Breslow JL
        • Hennekens CH
        • Buring JE
        • Willett WC
        • Krauss RM
        Low-density lipoprotein subclass patterns and risk of myocardial infarction.
        JAMA. 1988; 260: 1917
        • Campos H
        • Genest JJ
        • Blijlevens E
        • et al.
        Low density lipoprotein particle size and coronary artery disease.
        Arterioscler Thromb. 1992; 12: 187
        • Coresh J
        • Kwiterovich PJ
        • Smith HH
        • Bachorik PS
        Association of plasma triglyceride concentration and LDL particle diameter, density, and chemical composition with premature coronary artery disease in men and women.
        J Lipid Res. 1993; 34: 1687
        • Griffin BA
        • Freeman DJ
        • Tait GW
        • et al.
        Role of plasma triglyceride in the regulation of plasma low density lipoprotein (LDL) subfractions: relative contribution of small, dense LDL to coronary heart disease risk.
        Atherosclerosis. 1994; 106: 241
        • Nikkila M
        • Solakivi T
        • Lehtimaki T
        • Koivula T
        • Laippala P
        • Astrom B
        Postprandial plasma lipoprotein changes in relation to apolipoprotein E phenotypes and low density lipoprotein size in men with and without coronary artery disease.
        Atherosclerosis. 1994; 106: 149
        • Tornvall P
        • Karpe F
        • Carlson LA
        • Hamsten A
        Relationships of low density lipoprotein subfractions to angiographically defined coronary artery disease in young survivors of myocardial infarction.
        Atherosclerosis. 1991; 90: 67
        • Austin MA
        • Brunzell JD
        • Fitch WL
        • Krauss RM
        Inheritance of low density lipoprotein subclass patterns in familial combined hyperlipidemia.
        Arteriosclerosis. 1990; 10: 520
        • Austin MA
        • Newman B
        • Selby JV
        • Edwards K
        • Mayer EJ
        • Krauss RM
        Genetics of LDL subclass phenotypes in women twins. Concordance, heritability, and commingling analysis.
        Arterioscler Thromb. 1993; 13: 687
        • Crouse III, J
        • Byington RP
        • Bond MG
        • et al.
        Pravastatin, lipids, and atherosclerosis in the carotid arteries (PLAC-II).
        Am J Cardiol. 1995; 75: 455
        • Jansen H
        • Hop W
        • Van TA
        • Bruschke AV
        • Birkenhager JC
        Hepatic lipase and lipoprotein lipase are not major determinants of the low density lipoprotein subclass pattern in human subjects with coronary heart disease.
        Atherosclerosis. 1994; 107: 45
        • Austin MA
        Low-density lipoprotein subclass phenotypes and familial combined hyperlipidemia.
        Diabetes Metab Rev. 1991; 7: 173
        • Crouse JR
        • Parks JS
        • Schey HM
        • Kahl FR
        Studies of low density lipoprotein molecular weight in human beings with coronary artery disease.
        J Lipid Res. 1985; 26: 566
      1. Dart AM, Cameron JD. Effects of coronary risk factors on aortic and arterial properties in man. In, Functional Abnormalities of the Aorta. Ed, Boudoulas H, Toutouzas PK, Wooley CF. Futura Publishing Co, NY, 1995, p 353.

      2. Sattler W, Bone P, Stocker R. Isolation of human VLDL, LDL, HDL and two HDL subclasses in the TL-100 tabletop centrifuge using the TLA-100.4 rotor, Beckman Instruments Technical Bulletin, DS-850 (1992).

        • Campos H
        • Roederer G
        • Lussier-Cacan S
        • Davignon J
        • Krauss R
        Predominance of large LDL and reduced HDL2 cholesterol in normolipidemic men with coronary artery disease.
        Arterioscler Thromb Vasc Biol. 1995; 15: 1043
        • Ginsberg HN
        • Jones J
        • Blaner WS
        • et al.
        Association of postprandial triglyceride and retinyl palmitate responses with newly diagnosed exercise-induced myocardial ischemia in middle-aged men and women.
        Arterioscler Thromb Vasc Biol. 1995; 15: 1829
        • Detry JM
        • Kapita BM
        • Cosyns J
        • Sottiaux B
        • Brasseur LA
        • Rousseau MF
        Diagnostic value of history and maximal exercise electrocardiography in men and women suspected of coronary heart disease.
        Circulation. 1977; 56: 756
        • LaBelle M
        • Krauss RM
        Differences in carbohydrate content of low density lipoproteins associated with low density lipoprotein subclass patterns.
        J Lipid Res. 1990; 31: 1577
        • Williams PT
        • Vranizan KM
        • Krauss RM
        Correlations of plasma lipoproteins with LDL subfractions by particle size in men and women.
        J Lipid Res. 1992; 33: 765
        • Fisher WR
        • Zech LA
        • Bardalaye P
        • Warmke G
        • Berman M
        The metabolism of apolipoprotein B in subjects with hypertriglyceridemia and polydisperse LDL.
        J Lipid Res. 1980; 21: 760
        • Yamashita S
        • Matsuzawa Y
        • Okazaki M
        • et al.
        Small polydisperse low density lipoproteins in familial hyperalphalipoproteinemia with complete deficiency of cholesteryl ester transfer activity.
        Atherosclerosis. 1988; 70: 7
        • Hirano K
        • Matsuzawa Y
        • Sakai N
        • et al.
        Polydisperse low-density lipoproteins in hyperalphalipoproteinemic chronic alcohol drinkers in association with marked reduction of cholesteryl ester transfer protein activity.
        Metabolism. 1992; 41: 1313
        • Gambert P
        • Bouzerand GC
        • Athias A
        • Farnier M
        • Lallemant C
        Human low density lipoprotein subfractions separated by gradient gel electrophoresis: composition, distribution, and alterations induced by cholesteryl ester transfer protein.
        J Lipid Res. 1990; 31: 1199
        • Lagrost L
        • Gandjini H
        • Athias A
        • Guyard DV
        • Lallemant C
        • Gambert P
        Influence of plasma cholesteryl ester transfer activity on the LDL and HDL distribution profiles in normolipidemic subjects.
        Arterioscler Thromb. 1993; 13: 815
        • Lagrost L
        • Gambert P
        • Lallemant C
        Combined effects of lipid transfers and lipolysis on gradient gel patterns of human plasma LDL.
        Arterioscler Thromb. 1994; 14: 1327
        • McNamara JR
        • Jenner JL
        • Li Z
        • Wilson PW
        • Schaefer EJ
        Change in LDL particle size is associated with change in plasma triglyceride concentration.
        Arterioscler Thromb. 1992; 12: 1284
        • Austin MA
        • King MC
        • Vranizan KM
        • Krauss RM
        Atherogenic lipoprotein phenotype. A proposed genetic marker for coronary heart disease risk.
        Circulation. 1990; 82: 495
        • Austin MA
        • Krauss RM
        Genetic control of low-density-lipoprotein subclasses.
        Lancet. 1986; 2: 592
        • Campos H
        • Blijlevens E
        • McNamara JR
        • et al.
        LDL particle size distribution. Results from the Framingham Offspring Study.
        Arterioscler Thromb. 1992; 12: 1410
        • Dreon DM
        • Fernstrom HA
        • Miller B
        • Krauss RM
        Low-density lipoprotein subclass patterns and lipoprotein response to a reduced-fat diet in men.
        Faseb J. 1994; 8: 121
        • Parks JS
        • Bullock BC
        Effect of fish oil versus lard diets on the chemical and physical properties of low density lipoproteins of nonhuman primates.
        J Lipid Res. 1987; 28: 173
        • Parks JS
        • Gebre AK
        Studies on the effect of dietary fish oil on the physical and chemical properties of low density lipoproteins in cynomolgus monkeys.
        J Lipid Res. 1991; 32: 305
        • Rudel LL
        • Bond MG
        • Bullock BC
        LDL heterogeneity and atherosclerosis in nonhuman primates.
        Ann NY Acad Sci. 1985; 454: 248
        • Campos H
        • Willett WC
        • Peterson RM
        • et al.
        Nutrient intake comparisons between Framingham and rural and urban Puriscal, Costa Rica. Associations with lipoproteins, apolipoproteins, and low density lipoprotein particle size.
        Arterioscler Thromb. 1991; 11: 1089
        • Campos H
        • Bailey SM
        • Gussak LS
        • Siles X
        • Ordovas JM
        • Schaefer EJ
        Relations of body habitus, fitness level, and cardiovascular risk factors including lipoproteins and apolipoproteins in a rural and urban Costa Rican population.
        Arterioscler Thromb. 1991; 11: 1077
        • Swan JW
        • Walton C
        • Godsland IF
        • Crook D
        • Oliver MF
        • Stevenson JC
        Insulin resistance syndrome as a feature of cardiological syndrome X in non-obese men.
        Br Heart J. 1994; 71: 41
        • Inchiostro S
        • Bertoli G
        • Zanette G
        • Donadon V
        Evidence of higher insulin resistance in NIDDM patients with ischaemic heart disease.
        Diabetologia. 1994; 37: 597
        • Slowinska SJ
        • Malczewska B
        • Srzednicki M
        • et al.
        Hyperinsulinaemia and decreased plasma levels of dehydroepiandrosterone sulfate in premenopausal women with coronary heart disease.
        J Int Med Res. 1995; 237: 465
        • Nosadini R
        • Manzato E
        • Solini A
        • et al.
        Peripheral, rather than hepatic, insulin resistance and atherogenic lipoprotein phenotype predict cardiovascular complications in NIDDM.
        Eur J Clin Invest. 1994; 24: 258
        • Stern MP
        Diabetes and cardiovascular disease. The ‘common soil’ hypothesis.
        Diabetes. 1995; 44: 369
        • Rajman I
        • Maxwell S
        • Cramb R
        • Kendall M
        Particle size: the key to the atherogenic lipoprotein?.
        Q J Med. 1994; 87: 709