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Small, dense low-density lipoprotein as a risk factor for coronary heart disease

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International Journal of Clinical and Laboratory Research

Summary

Data from case-control and cross-sectional studies uniformly demonstrate an association between small, dense low-density lipoprotein and risk of coronary heart disease. This relationship may be attributable to the association of small, dense low-density lipoprotein with other atherogenic lipoproteins, the presence of the insulin resistance syndrome in subjects with small low-density lipoprotein, and/or the increased oxidative susceptibility of small, dense low-density lipoprotein particles. Furthermore, because small low-density lipoprotein appears to be a common trait in the general population, more than one of these atherogenic mechanisms may be operating simulataneously to increase risk of coronary heart disease.

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References

  1. National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults. Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation and treatment of high blood cholesterol in adults (adult treatment panel II). JAMA 1993; 269:3015.

    Article  Google Scholar 

  2. Krauss RM. Low-density lipoprotein subclasses and risk of coronary artery disease. Curr Opin Lipidol 1991; 2:248.

    Article  CAS  Google Scholar 

  3. Cheung MC, Brown BG, Wolf AC, Albers, JJ. Altered particle size distribution of apolipoprotein A-I-containing lipoproteins in subjects with coronary artery disease. J Lipid Res 1991; 32:383.

    PubMed  CAS  Google Scholar 

  4. Steiner G, Schwartz L, Shumak S, Poapst M. The association of increased levels of intermediate-density lipoproteins with smoking and coronary artery disease. Circulation 1987; 75:124.

    PubMed  CAS  Google Scholar 

  5. Utermann G. The mysteries of lipoprotein(a). Science 1989; 246:904.

    Article  PubMed  CAS  Google Scholar 

  6. Fisher WR. Heterogeneity of plasma low density lipoproteins manifestations of the physiologic phenomenon in man. Metabolism 1983; 32:283.

    Article  PubMed  CAS  Google Scholar 

  7. Crouse JR, Parks JS, Schey HM. Studies of low density lipoprotein molecular weight in human beings with coronary arery disease. J Lipid Res 1985; 26:566.

    PubMed  CAS  Google Scholar 

  8. Austin MA, Breslow JL, Hennekens CH, Buring JE, Willett WS, Krauss RM. Low-density lipoprotein subclass patterns and risk of myocardial infarction. JAMA 1988; 260:1917.

    Article  PubMed  CAS  Google Scholar 

  9. Tornvall P, Karpe F, Carlson LA, Hamsten A. Relationship of low density lipoprotein subfractions to angiographically defined coronary artery disease in young survivors of myocardial infarction. Atherosclerosis 1991; 90:67.

    Article  PubMed  CAS  Google Scholar 

  10. Krauss RM, Burke DJ. Identification of multiple subclasses of plasma low-density lipoproteins in normal humans. J Lipid Res 1982; 23:97.

    PubMed  CAS  Google Scholar 

  11. Nichols AV, Krauss RM, Musliner TA. Nondenaturing poly-acrylamide gradient gel electrophoresis. In: Segrest JP, Albers JJ, eds. Methods in enzymology, vol 128. Plasma lipoproteins, part A. Preparation, structure and molecular biology, Orlando: Academic Press, 1986; 417–431.

    Chapter  Google Scholar 

  12. Austin MA, King M-C, Vranizan KM, Krauss RM. Atherogenic lipoprotein phenotype: a proposed genetic marker for coronary heart disease risk. Circulation 1990; 82:495.

    PubMed  CAS  Google Scholar 

  13. Campos H, Genest JJ, Jr, Blijlevens E, McNamara JR, Jenner JL, Ordovas JM, Wilson PWF, Schaefer EJ. Low density lipoprotein particle size and coronary artery disease. Arterioscler Thromb 1992; 12:187.

    PubMed  CAS  Google Scholar 

  14. Giffin BA, Caslake MJ, Yip B, Tait GW, Packard CJ, Shepherd J. Rapid isolation of low density lipoprotein (LDL) subfractions from plasma by density gradient ultracentrifugation. Atherosclerosis 1990; 83:59.

    Article  Google Scholar 

  15. Jaakkola O, Solakivi T, Tertov VV, Orekhov AN, Miettinen TA, Nikkari T. Characteristics of low-density lipoprotein subfractions from patients with coronary artery disease. Coron Artery Dis 1993; 4:379.

    Article  PubMed  CAS  Google Scholar 

  16. Coresh J, Kwiterovich PO, Bachorik P. Association of low density lipoprotein size, density and composition with premature coronary arery disease. J Lipid Res 1993; 34:1687.

    PubMed  CAS  Google Scholar 

  17. Austin MA, Brunzell JD, Fitch WL, Krauss RM. Inheritance of low density lipoprotein subclass patterns in familial combined hyperlipidemia. Atherosclerosis 1990; 10:520.

    CAS  Google Scholar 

  18. Selby JV, Austin MA, Newman B, Mayer EJ, Krauss RM. LDL subclass phenotypes and the insulin resistance syndrome in women. Circulation 1993; 88:381.

    PubMed  CAS  Google Scholar 

  19. Haffner SM, Mykkanen L, Valdez RA, Paidi M, Stern MP, Howard BV. LDL size and patients pattern in a biethnic population. Arterioscler Thromb 1993; 13:1623.

    PubMed  CAS  Google Scholar 

  20. McNamara JR, Jenner JL, Zhengling L, Wilson PWF, Schaefer EJ. Change in LDL particle size is associated with change in plasma triglyceride concentration. Arterioscler Thromb 1992; 12:1284.

    PubMed  CAS  Google Scholar 

  21. Stern MP. The insulin resistance syndrome. In: Alberti KGMM, DeFronzo RA, Zimmet P, eds. International textbook of diabetes mellitus. Chichester: Wiley. In press.

  22. Ducimetiere P, Eschwege E, Papoz L, Richards JL, Claude JR, Rosselin GE. Relationship of plasma insulin levels to the incidence of myocardial infarction and coronary heart disease mortality in a middle-aged population. Diabetologia 1980; 19:205.

    Article  PubMed  CAS  Google Scholar 

  23. Fontbonne A, Charles MA, Thibult N, Richard JL, Claude JR, Warnet JM, Rosselin GE, Eschwege E. Hyperinsulinaemia as a predictor of coronary heart disease mortality in a healthy population: the Paris Prospective Study, 15-year follow-up. Diabetoligia 1991; 34:356.

    Article  CAS  Google Scholar 

  24. Pyrola K. Relationship of glucose tolerance and plasma insulin to the incidence of coronary heart disease: results from two population studies in Finland. Diabetes Care 1979; 2:131.

    Article  Google Scholar 

  25. Welborn TA, Wearne K. Coronary heart disease incidence and cardiovascular mortality in Busselton with reference to glucose and insulin concentration. Diabetes Care 1979; 2:154.

    Article  PubMed  CAS  Google Scholar 

  26. Reaven GM. Role of insulin in human disease. Diabetes 1988; 37:1595.

    Article  PubMed  CAS  Google Scholar 

  27. Kaplan NM. The deadly quartet: upper-body obesity, glucose intolerance, hypertriglyceridemia, and hypertension. Arch Intern Med 1989; 149:1514.

    Article  PubMed  CAS  Google Scholar 

  28. DeFronzo RA, Ferrannini E. Insulin resistance: a multificated syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 1991; 14:173.

    Article  PubMed  CAS  Google Scholar 

  29. Swinkels DW, Denmacker PNM, Hendriks JCM, Laar A van 't. Low density lipoprotein subfractions and relationship to other risk factors for coronary artery disease in healthy individuals. Arteriosclerosis 1989; 9:604.

    PubMed  CAS  Google Scholar 

  30. Reaven GM, Chen Y-DI, Jeppesen J, Maheux P, Krauss RM. Insulin resistance and hyperinsulinemia in individuals with small, dense low density lipoprotein particles. J Clin Invest 1993; 92:141.

    PubMed  CAS  Google Scholar 

  31. Haffner S, Howard B, Stern M. Small dense LDL are associated with the insulin resistance syndrome in the San Antonio Heart Study (abstract). Circulation 1993; 8 [Suppl I]:I125.

    Google Scholar 

  32. Barakat HA, Carpenter JW, McLendon VD, Khazanie P, Leggett N, Heath J, Marks R. Influence of obesity, impaired glucose tolerance and NIDDM on LDL structure and composition: possible link between hyperinsulinemia and atherosclerosis. Diabetes 1990; 39:1527.

    Article  PubMed  CAS  Google Scholar 

  33. Feingold KR, Grunfeld C, Pang M, Doerrler W, Krauss RM. LDL subclass phenotypes and triglyceride metabolism in non-insulin-dependent diabetes. Arterioscler Thromb 1992; 12:1496.

    PubMed  CAS  Google Scholar 

  34. Graaf J de, Hak-Lemmers HLM, Hectors MPC, Demacker PNM, Hendricks JCM, Stalenhoef AFH. Enhanced susceptibility to in vitro oxidation of the dense low density lipoprotein subfraction in healthy subjects. Arterioscler Thromb 1991; 11:298.

    PubMed  Google Scholar 

  35. Esterbauer H, Striegl G, Puhl H, Rotheneder M. Continuous monitoring of in vitro oxidation of human low density lipoprotein. Free Radic Res Commun 1989; 6:67.

    PubMed  CAS  Google Scholar 

  36. Tribble DL, Holl LG, Wood PD, Krauss RM. Variations in oxidative susceptibility among six low density lipoprotein subfractions of differing density and particle size. Atherosclerosis 1992; 93:189.

    Article  PubMed  CAS  Google Scholar 

  37. Dejager S, Bruckert E, Chapman MJ. Dense low density lipoprotein subspecies with diminished oxidative resistance predominate in combined hyperlipidemia. J Lipid Res 1993; 34:295.

    PubMed  CAS  Google Scholar 

  38. Graaf J de, Hendriks JCM, Demacker PNM, Stahlenhoef AFH. Identification of multiple dense LDL subfractions with enhanced susceptibility to in vitro oxidation among hypertriglyceridemic subjects. Normalization after clofibrate treatment. Arterioscler Thromb 1993; 13:712.

    PubMed  Google Scholar 

  39. Goldstein JL, Schrott HG, Hazzard WR, Bierman EL, Motulsky AG. Hyperlipidemia in coronary heart disease. II. Genetic analysis in 176 families and delineation of a new inherited disorder, combined hyperlipidemia. J Clin Invest 1973; 52:1544.

    Article  PubMed  CAS  Google Scholar 

  40. Chait A, Brzag RL, Tribble DL, Krauss RM. Susceptibility of small, dense, low-density lipoproteins to oxidative modification in subjects with the atherogenic lipoprotein phenotype, pattern B. Am J Med 1993; 94:350.

    Article  PubMed  CAS  Google Scholar 

  41. Kim RS, LaBella FS. Comparison of analytical methods for monitoring autooxidation profiles of authentic lipids. J Lipid Res 1987; 28:1110.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Epidemiology, School of Public Health and Community Medicine, SC-36, 1959 N.E. Pacific Avenue, USA

    M. A. Austin

  2. University of Washington, 98195, Seattle, WA, USA

    M. A. Austin

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Austin, M.A. Small, dense low-density lipoprotein as a risk factor for coronary heart disease. Int J Clin Lab Res 24, 187–192 (1994). https://doi.org/10.1007/BF02592460

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