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Apolipoprotein A-1 predicts coronary heart disease only at low concentrations of high-density lipoprotein cholesterol: an epidemiological study of Japanese-Americans

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International Journal of Clinical and Laboratory Research

Abstract

Conventional epidemiological and clinical studies of apolipoprotein A-1 and high-density lipoprotein-cholesterol have demonstrated, when examined jointly, that high-density lipoprotein is a better predictor of coronary heart disease. This strategy does not take into account known lipid metabolic relationships. A statistical approach that takes into account apoliprotein A-1 being a constituent of the high-density lipoprotein particle is more appropriate. Among 1,177 Japanese-American men of the Honolulu Heart Program cohort free of disease at baseline (1980–1982), 182 new coronary heart disease cases developed over a 12-year follow-up period. After removing the linear relationship with high-density lipoprotein-cholesterol, a relative measure of apoliprotein A-1 concentration was derived. Based on joint conditions of ‘low’ and ‘high’ relative apoliprotein A-1 concentration and ≤40 and >40 mg/dl for the high-density lipoprotein-cholesterol distribution, four groupings were created. Among relative joint groupings of high/≤40, low/≤40, high/>40, and low/>40, respectively, the 12-year coronary heart disease incidence varied from 28.6, 18.2, 8.3, to 11.7 cases per 1,000 person-years. A test of statistical interaction was significant (P=0.028). Additional analyses revealed coronary heart disease cases were more likely among men with triglycerides >190 mg/dl. Observed patterns of relationships among relative apoliprotein A-1 level, high-density lipoprotein cholesterol, and triglycerides with incident coronary heart disease are consistent with patterns noted in clinical, laboratory, and transgenic animal research more capable of elucidating mechanisms of disease causation. This epidemiological study suggests similar mechanisms may be operating at a population level, and may contribute to the public health burden of coronary heart disease.

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References

  1. Kunitake ST, O’Connor P, Naya-Vigne J. Heterogeneity of high-density lipoproteins and apolipoprotein A-I as related to quantification of apolipoprotein A-I. Methods Enzymol 1996; 263:260.

    Article  PubMed  CAS  Google Scholar 

  2. Fielding CJ, Fielding PE. Molecular physiology of reverse cholesterol transport. J Lipid Res 1995; 36:211.

    PubMed  CAS  Google Scholar 

  3. Leroy A, Dallongeville J, Fruchart JC. Apolipoprotein A-I-containing lipoproteins and atherosclerosis. Curr Opin Lipidol 1995; 6:281.

    Article  PubMed  CAS  Google Scholar 

  4. Castro GR, Fielding CJ. Early incorporation of cell-derived cholesterol into pre-beta-migrating high-density lipoprotein. Biochemistry 1988; 27:25.

    Article  PubMed  CAS  Google Scholar 

  5. Avogaro P, Bon GB, Cazzolato G, Quinci GB. Are apolipoproteins better discriminators than lipids for atherosclerosis? Lancet 1979; I:901.

    Article  Google Scholar 

  6. Buring JE, O’Connor GT, Goldhaber SZ, Rosner B, Herbert PN, Blum CB, et al. Decreased HDL2 and HDL3 cholesterol, Apo A-I and Apo A-II, and increased risk of myocardial infarction. Circulation 1992; 85:22.

    PubMed  CAS  Google Scholar 

  7. Coleman MP, Key TJ, Wang DY, Hermon C, Fentiman IS, Allen DS, et al. A prospective study of obesity, lipids, apolipoproteins and ischaemic heart disease in women. Atherosclerosis 1992; 92:177.

    Article  PubMed  CAS  Google Scholar 

  8. Cremer P, Nagel D, Labrot B, Mann H, Muche R, Elster H, et al. Lipoprotein Lp(a) as predictor of myocardial infarction in comparison to fibrinogen, LDL cholesterol and other risk factors: results from the prospective Gottingen Risk Incidence and Prevalence Study (GRIPS). Eur J Clin Invest 1994; 24:444.

    PubMed  CAS  Google Scholar 

  9. Durrington PN, Ishola M, Hunt L, Arrol S, Bhatnagar D. Apolipoproteins (a), AI, and B and parental history in men with early onset ischaemic heart disease. Lancet 1988; 1:1070.

    Article  PubMed  CAS  Google Scholar 

  10. Genest J Jr, McNamara JR, Ordovas JM, Jenner JL, Silberman SR, Anderson KM, et al. Lipoprotein cholesterol, apolipoprotein A-I and B and lipoprotein (a) abnormalities in men with premature coronary artery disease. J Am Coll Cardiol 1992; 19:792.

    Article  PubMed  Google Scholar 

  11. Genest JJ Jr, Bard JM, Fruchart JC, Ordovas JM, Wilson PF, Schaefer EJ. Plasma apolipoprotein A-I, A-II, B, E and C-III containing particles in men with premature coronary artery disease. Atherosclerosis 1991; 90:149.

    Article  PubMed  Google Scholar 

  12. Ishikawa T, Fidge N, Thelle DS, Forde OH, Miller NE. The Tromso Heart Study: serum apolipoprotein AI concentration in relation to future coronary heart disease. Eur J Clin Invest 1978; 8:179.

    Article  PubMed  CAS  Google Scholar 

  13. Johansson S, Bondjers G, Fager G, Wedel H, Tsipogianni A, Olofsson SO, et al. Serum lipids and apolipoprotein levels in women with acute myocardial infarction. Arteriosclerosis 1988; 8:742.

    PubMed  CAS  Google Scholar 

  14. Klausen IC, Sjol A, Hansen PS, Gerdes LU, Moller L, Lemming L, et al. Apolipoprotein(a) isoforms and coronary heart disease in men: a nested case-control study. Atherosclerosis 1997; 132:77.

    Article  PubMed  CAS  Google Scholar 

  15. Reinhart RA, Gani K, Arndt MR, Broste SK. Apolipoproteins A-I and B as predictors of angiographically defined coronary artery disease. Arch Intern Med 1990; 150:1629.

    Article  PubMed  CAS  Google Scholar 

  16. Salonen JT, Salonen R, Penttila I, Herranen J, Jauhiainen M, Kantola M, et al. Serum fatty acids, apolipoproteins, selenium and vitamin antioxidants and the risk of death from coronary artery disease. Am J Cardiol 1985; 56:226.

    Article  PubMed  CAS  Google Scholar 

  17. Stampfer MJ, Sacks FM, Salvini S, Willett WC, Hennekens CH. A prospective study of cholesterol, apolipoproteins, and the risk of myocardial infarction. N Engl J Med 1991; 325:373.

    PubMed  CAS  Google Scholar 

  18. Patsch W, Sharrett AR, Sorlie PD, Davis CE, Brown SA. The relation of high density lipoprotein cholesterol and its subfractions to apolipoprotein A-I and fasting triglycerides: the role of environmental factors. The Atherosclerosis Risk in Communities (ARIC) Study. Am J Epidemiol 1992; 136:546.

    PubMed  CAS  Google Scholar 

  19. Miller NE. Associations of high-density lipoprotein subclasses and apolipoproteins with ischemic heart disease and coronary atherosclerosis. Am Heart J 1987; 113:589.

    Article  PubMed  CAS  Google Scholar 

  20. Worth RM, Kagan A. Ascertainment of men of Japanese ancestry in Hawaii through World War II selective service registration. J Chronic Dis 1970; 23:389.

    Article  PubMed  CAS  Google Scholar 

  21. Yano K, Reed DM, McGee DL. Ten-year incidence of coronary heart disease in the Honolulu Heart Program. Relationship to biologic and lifestyle characteristics. Am J Epidemiol 1984; 119:653.

    PubMed  CAS  Google Scholar 

  22. Castelli WP, Doyle JT, Gordon T, Hames CG, Hjortland MC, Hulley SB, et al. HDL cholesterol and other lipids in coronary heart disease. The cooperative lipoprotein phenotyping study. Circulation 1977; 55:767.

    PubMed  CAS  Google Scholar 

  23. Reed D, Yano K, Kagan A. Lipids and lipoproteins as predictors of coronary heart disease, stroke, and cancer in the Honolulu Heart Program. Am J Med 1986; 80:871.

    Article  PubMed  CAS  Google Scholar 

  24. Rhoads GG, Gulbrandsen CL, Kagan A. Serum lipoproteins and coronary heart disease in a population study of Hawaii Japanese men. N Engl J Med 1976; 294:293.

    PubMed  CAS  Google Scholar 

  25. Albers JJ, Warnick GR, Johnson N, Bachorik PS, Muesing R, Lippel K, et al. Quality control of plasma high-density lipoprotein cholesterol measurement methods. Circulation 1980; 62:IV9.

    Google Scholar 

  26. Curb JD, Reed DM, Yano K, Kautz JA, Albers JJ. Plasma lipids and lipoproteins in elderly Japanese-American men. J Am Geriatr Soc 1986; 34:773.

    PubMed  CAS  Google Scholar 

  27. Lipid Research Clinic Program. Manual of Laboratory Operations, vol 1. Lipid and lipoprotein analysis. (NIH) 75628. Washington, D.C.: Department of Health, Education, and Welfare, U.S. Government Printing Office, 1974

    Google Scholar 

  28. Yano K, Reed DM, Curb JD, Hankin JH, Albers JJ. Biological and dietary correlates of plasma lipids and lipoproteins among elderly Japanese men in Hawaii. Arteriosclerosis 1986; 6:422.

    PubMed  CAS  Google Scholar 

  29. Wahl PW, Warnick GR, Albers JJ, Hoover JJ, Walden CE, Bergelin RO, et al. Distribution of lipoproteins triglyceride and lipoprotein cholesterol in an adult population by age, sex, and hormone use — The Pacific Northwest Bell Telephone Company health survey. Atherosclerosis 1981; 39:111.

    Article  PubMed  CAS  Google Scholar 

  30. Marcovina SM, Albers JJ, Henderson LO, Hannon WH. International Federation of Clinical Chemistry standardization project for measurements of apolipoproteins A-I and B. III. Comparability of apolipoprotein A-I values by use of international reference material. Clin Chem 1993; 39:773.

    PubMed  CAS  Google Scholar 

  31. Marascuilo LA, Levin JR. Multivariate statistics in the social sciences: A researcher’s guide. Monterey, California: Brooks/Cole, 1983.

    Google Scholar 

  32. SAS Institute. SAS/STAT Software: the PHREG procedure, version 6. Cary, N.C.: SAS Institute, 1991.

    Google Scholar 

  33. Armitage P, Berry G. Statistical methods in medical research, 2nd edn. Oxford: Blackwell Scientific Publications, 1987.

    Google Scholar 

  34. Rothman KJ. Modern epidemiology. Boston: Little, Brown, 1986.

    Google Scholar 

  35. Miida T, Inano K, Yamaguchi T, Tsuda T, Okada M. LpA-I levels do not reflect pre beta1-HDL levels in human plasma. Atherosclerosis 1997; 133:221.

    Article  PubMed  CAS  Google Scholar 

  36. Barrans A, Jaspard B, Barbaras R, Chap H, Perret B, Collet X. Pre-beta HDL: structure and metabolism. Biochim Biophys Acta 1996; 1300:73.

    PubMed  Google Scholar 

  37. Hara H, Yokoyama S. Role of apolipoproteins in cholesterol efflux from macrophages to lipid microemulsion: proposal of a putative model for the pre-beta high-density lipoprotein pathway. Biochemistry 1992; 31:2040.

    Article  PubMed  CAS  Google Scholar 

  38. Ishida BY, Frolich J, Fielding CJ. Prebeta-migrating high density lipoprotein: quantitation in normal and hyperlipidemic plasma by solid phase radioimmunoassay following electrophoretic transfer. J Lipid Res 1987; 28:778.

    PubMed  CAS  Google Scholar 

  39. Miida T, Nakamura Y, Inano K, Matsuto T, Yamaguchi T, Tsuda T, et al. Pre beta 1-high-density lipoprotein increases in coronary artery disease. Clin Chem 1996; 42:1992.

    PubMed  CAS  Google Scholar 

  40. Miida T, Kawano M, Fielding CJ, Fielding PE. Regulation of the concentration of pre beta high-density lipoprotein in normal plasma by cell membranes and lecithin-cholesterol acyltransferase activity. Biochemistry 1992; 31:11112.

    Article  PubMed  CAS  Google Scholar 

  41. Neary R, Bhatnagar D, Durrington P, Ishola M, Arrol S, Mackness M. An investigation of the role of lecithin:cholesterol acyltransferase and triglyceride-rich lipoproteins in the metabolism of pre-beta high density lipoproteins. Atherosclerosis 1991; 89:35.

    Article  PubMed  CAS  Google Scholar 

  42. Masucci-Magoulas L, Goldberg IJ, Bisgaier CL, Serajuddin H, Francone OL, Breslow JL, et al. A mouse model with features of familial combined hyperlipidemia. Science 1997; 275:391.

    Article  PubMed  CAS  Google Scholar 

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Sharp, D.S., Burchfiel, C.M., Rodriguez, B.L. et al. Apolipoprotein A-1 predicts coronary heart disease only at low concentrations of high-density lipoprotein cholesterol: an epidemiological study of Japanese-Americans. Int J Clin Lab Res 30, 39–48 (2000). https://doi.org/10.1007/s005990070032

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  • DOI: https://doi.org/10.1007/s005990070032

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