Lipid-lowering therapy — Implications for the prevention of atherosclerosis

  • G. Schmitz
  • K. J. Lackner
Conference paper


Lipid-lowering therapy has been advocated as a means to decrease the incidence of cardiovascular disease. The basis for this are results of animal studies, epidemiologic surveys, and intervention studies in man. There have been recommendations by national and international advisory boards regarding the aims and means of such interventional strategies. These have not been unanimously accepted, however. The present article will review the evidence on which intervention strategies may be based and the current status of the scientific discussion. The implications for future strategies to prevent atherosclerosis are discussed.

Key words

Lipoproteins prevention of atherosclerosis lipid-lowering therapy 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Arntzenius AC, Kromhout D, Barth JD, Reiber JHC, Bruschke AVG, Buis B, van Gent CM, Kempen-Voogd N, Strikwerda S, van der Velde EA(1985) Diet, lipoproteins, and the progression of coronary atherosclerosis. The Leiden Intervention Trial. N Engl J Med 312: 805–811Google Scholar
  2. 2.
    Berliner JA, Territo MC, Sevanian A, Ramin S, Kim JA, Bamshad B, Esterson M, Fogelman AM (1990) Minimally modified low density lipoprotein stimulates monocyte endotelial interactions. J Clin Invest 85: 1260–1266PubMedCrossRefGoogle Scholar
  3. 3.
    Blankenhorn DH, Nessim SA, Johnson RL, Sanmarco ME, Azen SP, Cashin-Hemphill L (1987) Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts. JAMA 257: 3233–3240PubMedCrossRefGoogle Scholar
  4. 4.
    Brenninkmeijer BJ, Stuyt PH, Demacker PN, Stalenhoef AF, van’t Laar A (1987) Catabolism of chylomicron remnants in normolipidemic subjects in relation to the apoprotein E phenotype. J Lipid Res 28: 361–370Google Scholar
  5. 5.
    Brown G, Albers JJ, Fisher LD, Schaefer SM, Lin JT, Kaplan C, Zhao XQ, Bisson BD, Fitzpatrick VF, Dodge HT(1990) Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med 323: 1289–98Google Scholar
  6. 6.
    Brown WV (1990) Dietary recommendations to prevent coronary heart disease. Ann N Y Acad Sci 598: 376–388PubMedCrossRefGoogle Scholar
  7. 7.
    Buchwald H, Fitch L, Moore RB (1982) Overview of randomized clinical trials of lipid intervention for atherosclerotic cardiovascular disease. Contr Clin Trials 3: 271–283CrossRefGoogle Scholar
  8. 8.
    Buchwald H, Varco RL, Matts JP, Long JM, Fitch LL, Campbell GS, Pearce MB, Yellin AE, Edmiston WA, Smink RD Jr, Sawin HS Jr, Campos CT, Hansen BJ, Tuna N, Karnegis JN, Sanmarco ME, Amplatz K, Castaneda-Zuniga WR, Hunter DW, Bissett JK, Weber FJ, Stevenson JW, Leon AS, Chalmers TC, and the POSCH group (1990) Effect of partial ideal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia. Report of the Program on the Surgical Control of the Hyperlipidemias (POSCH). N Engl J Med 323: 946–955PubMedCrossRefGoogle Scholar
  9. 9.
    Brunzell JD, Schrott HG, Motulsky AG, Bierman EL (1976) Myocardial infarction in the familial forms of hypertriglyceridemia. Metabolism 25: 313–320PubMedCrossRefGoogle Scholar
  10. 10.
    Canner PL, Berge KG, Wenger NK, Stamler J, Friedman L, Prineas RJ, Friedewald W (1986) Fifteen-year mortality in coronary drug project patients: long-term benefit with niacin. J Am Coll Cardiol 8: 1245–1255PubMedCrossRefGoogle Scholar
  11. 11.
    Carlson LA, Rosenhamer G (1988) Reduction of mortality in the Stockholm Ischaemic Heart Disease Secondary Prevention Study by combined treatment with Clofibrate and nicotinic acid. Acta Med Scand 223: 405–424PubMedCrossRefGoogle Scholar
  12. 12.
    Castelli WP, Garrison RJ, Wilson PWF, Abbott RD, Kalousdian S, Kannel WB (1986) Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham Study. JAMA 256: 2835–2838PubMedCrossRefGoogle Scholar
  13. 13.
    Consensus Conference (1985) Lowering blood cholesterol to prevent heart disease. JAMA 253: 2080–2086Google Scholar
  14. 14.
    Criqui MH (1991) Cholesterol, primary and secondary prevention, and all-cause mortality. Ann Intern Med 119: 973–976Google Scholar
  15. 15.
    The Coronary Drug Project Research Group (1975) Clofibrate and niacin in coronary heart disease. JAMA 231: 360–381CrossRefGoogle Scholar
  16. 16.
    Cumming AM, Robertson F (1984) Polymorphism of the apo E locus in relation to risk of coronary disease. Clin Genet 25: 310–313Google Scholar
  17. 17.
    Cushing SD, Berliner JA, Valente AJ, Territo MC, Navab M, Parhami F, Gerrity R, Schwartz CJ, Fogelman AM (1990) Minimally modified low density lipoprotein induces monocyte chemotactic protein 1 in human endothelial cells and smooth muscle cells. Proc Natl Acad Sci USA 87: 5134–5138PubMedCrossRefGoogle Scholar
  18. 18.
    Dahlen GH, Guyton JR, Attar M, Farmer JA, Kautz JA, Gotto AM Jr (1986) Association of levels of lipoprotein Lp(a), plasma lipids, and other lipoproteins with coronary artery disease documented by angiography. Circulation 74: 758–765PubMedCrossRefGoogle Scholar
  19. 19.
    Davignon J, Gregg RE, Sing CF (1988) Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis 8: 1–21Google Scholar
  20. 20.
    Ederer F, Leren P, Turpeinen O, Frantz ID Jr (1971) Cancer among men on cholesterol-lowering diets. Experience from five clinical trials. Lancet II: 203–206Google Scholar
  21. 21.
    European Atherosclerosis Society (1992) Prevention of coronary heart disease. Scientific background and new clinical guidelines. Nutr Metab Cardio vase Dis 2: 113–154Google Scholar
  22. 22.
    Frick MH, Elo O, Haapa K, Heinonen OP, Heinsalmi P, Helo P, Huttunen JK, Kaitaniemi P, Koskinen P, Manninen V, Mäenpäa H, Mälkönen M, Mänttäri M, Norola S, Pasternack A, Pikkarainen J, Romo M, SjöblomT, Nikkilä EA (1987) Helsinki heart study: primary- prevention trial with gemfibrozil in middle-aged men with dyslipidemia. N Engl J Med 317: 1237–1245Google Scholar
  23. 23.
    Garber AM, Littenberg B, Sox HC Jr, Wagner JL, Gluck M (1991) Costs and health consequences of cholesterol screening for asymptomatic older Americans. Arch Intern Med 151: 1089–1095PubMedCrossRefGoogle Scholar
  24. 24.
    Goldstein JL, Brown MS (1989) Familial hypercholesterolemia. In: The metabolic basis of inherited disease. Scriver CR, Beaudet AL, Sly WS, Valle D (eds), McGraw-Hill, pp 1215–1250Google Scholar
  25. 25.
    Goldstein JL, Schrott HG, Hazzard WR, Bierman EL, Motulsky AG (1973) Hyperlipidemia in coronary heart disease. II. Genetic analysis in 176 families and delineation of a new inherited disorder, combined hyperlipidemia. J Clin Invest 52: 1544–1568PubMedCrossRefGoogle Scholar
  26. 26.
    Gordon DJ, Probstfield JL, Garrison RJ, Neaton JD, Castelli WP, Knoke JD, Jacobs DR, Bangdiwala S, Tyroler HA (1989) High-density lipoprotein cholesterol and cardiovascular disease. Circulation 79: 8–15PubMedCrossRefGoogle Scholar
  27. 27.
    Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR (1977) High density lipoprotein as a protective factor against coronary heart disease. Am J Med 62: 707–714PubMedCrossRefGoogle Scholar
  28. 28.
    Grundy SM (1987) Dietary therapy for different forms of hyperlipoproteinemia. Circulation 76: 523–528PubMedCrossRefGoogle Scholar
  29. 29.
    Grundy SM (1990) Cholesterol and coronary heart disease. Future directions. JAMA 264: 3053–3059PubMedCrossRefGoogle Scholar
  30. 30.
    Haynes RB, Sackett DL, Taylor DW, Gibson ES, Johnson AL (1978) Increased absenteeism from work after detection and labelling of hypertensive patients. N Engl Med 299: 741–744CrossRefGoogle Scholar
  31. 31.
    Kesaniemi YA, Ehnholm C, Miettinen TA (1987) Intestinal cholesterol absorption efficiency in man is related to apolipoprotein E phenotype. J Clin Invest 80: 578–581CrossRefGoogle Scholar
  32. 32.
    Krahn M, Naylor CD, Basinski AS, Detsky AS (1991) Comparison of an aggressive (U.S.) and a less aggressive (Canadian) policy for cholesterol screening and treatment. Ann Int Med 115: 248–255PubMedGoogle Scholar
  33. 33.
    Kronmal RA (1985) Commentary on the published results of the Lipid Research Clinics Primary Prevention Trial. JAMA 253: 2091–2093PubMedCrossRefGoogle Scholar
  34. 34.
    Lackner KJ, Schettler G, Kiibler W (1989) Plasma cholesterol, lipid lowering, and risk for cancer. An update of the results from epidemiologic studies and intervention trials. Klin Wochenschr 67: 957–962PubMedCrossRefGoogle Scholar
  35. 35.
    Leren P (1970) The Oslo Diet-Heart Study. Circulation 42: 935–942PubMedGoogle Scholar
  36. 36.
    Levy RI, Brensike JF, Epstein SE, Kelsey SF, Passamani ER, Richardson JM, Loh IK, Stone NJ, Aldrich RF, Battaglini JW, Moriarity DJ, Fisher ML, Friedman L, Friedewald W, Detre KM (1984) The influence of changes in lipid values induced by cholestyramine and diet on progression of coronary artery disease: the results of the NHLBI type II coronary intervention study. Circulation 69: 325–337PubMedCrossRefGoogle Scholar
  37. 37.
    The Lipid Research Clinics Program (1984) The lipid research clinics coronary primary prevention trial results. I. Reduction in incidence of coronary heart disease. JAMA 251: 351–364Google Scholar
  38. 38.
    The Lipid Research Clinics Program (1984) The lipid research clinics coronary primary prevention trial results. II. The relationship of reduction in incidence of coronary heart disese to cholesterol lowering. JAMA 251: 365–374Google Scholar
  39. 39.
    Lloyd JK (1991) Cholesterol: should we screen all children or change the diet of all children. Acta Paediatr Scand suppl 373: 66–72PubMedCrossRefGoogle Scholar
  40. 40.
    Lussier-Cacan S, Bouthillier D, Davignon J (1985) ApoE allele frequency in primary endogenous hypertriglyceridemia (type IV) with and without hyperapobetalipo- proteinemia. Arteriosclerosis 5: 639–643PubMedCrossRefGoogle Scholar
  41. 41.
    Mahley RW (1988) Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science 240: 622–630PubMedCrossRefGoogle Scholar
  42. 42.
    Mahley RW, Rail SC Jr (1989) Type III hyperlipoproteinemia (dysbetalipoproteinemia): the role of apolipoprotein E in normal and abnormal lipoprotein metabolism. In: The metabolic basis of inherited disease. Scriver CR, Beaudet AL, Sly WS, Valle D (eds), McGraw-Hill, pp 1195–1214Google Scholar
  43. 43.
    Menzel H-J, Kladetzky R-G, Assmann G (1983) Apolipoprotein E polymorphism and coronary artery disease. Arteriosclerosis 3: 310–315Google Scholar
  44. 44.
    Mitchell JR (1990) What do we gain by modifying risk factors for coronary disease? Schweiz Med Wochenschr 120: 359–364PubMedGoogle Scholar
  45. 45.
    Mossey JM (1981) Psychosocial consequences of labelling in hypertension. Clin Invest Med 201–207Google Scholar
  46. 46.
    Muldoon MF, Manuck SB, Matthews KA (1990) Lowering cholesterol concentrations and mortality: a quantitative review of primary prevention trials. Br Med J 301: 309–314CrossRefGoogle Scholar
  47. 47.
    Newman TB, Browner WS, Hulley SB (1990) The case against childhood screening. JAMA 264: 3039–3043PubMedCrossRefGoogle Scholar
  48. 48.
    Oliver MF (1992) Doubts about preventing coronary heart disease. Br Med J 304: 393–394CrossRefGoogle Scholar
  49. 49.
    Oliver MF, Heady J A, Morris JN, Cooper J (1978) A cooperative trial in the primary prevention of ischemic heart disease using clofibrate. Br Heart J 40: 1069–1076CrossRefGoogle Scholar
  50. 50.
    Parthasarathy S, Steinberg D, Witztum JL (1992) The role of oxidized low-density lipoproteins in the pathogenesis of atherosclerosis. Ann Rev Med 43: 219–225PubMedCrossRefGoogle Scholar
  51. 51.
    RajavahisthTB, Andalibi A, Territo MC, Berliner JA, Navab M, Fogelman AM, Lusis AJ (1990) Induction of endothelial cell expression of granulocyte and macrophage colony- stimulating factors by modified low-density lipoproteins. Nature 344: 254–257CrossRefGoogle Scholar
  52. 52.
    Ramsay LE, Yeo WW, Jackson PR (1991) Dietary reduction of serum cholesterol concentration: time to think again. Br Med J 303: 953–957CrossRefGoogle Scholar
  53. 53.
    Rauh G, Keller C, Schuster H, Wolfram G, Zollner N (1992) Familial defective apolipoprotein B–100: a common cause of primary hypercholesterolemia. Clin Investig 70: 77–84PubMedCrossRefGoogle Scholar
  54. 54.
    Reckless JPD (1987) Can nutrition favourably affect serum lipids? Proc Nutr Soc 46: 361–366PubMedCrossRefGoogle Scholar
  55. 55.
    Report of the National Cholesterol Education Program Expert Panel on the detection, evaluation, and treatment of high blood cholesterol in adults (1988). Arch Intern Med 148: 36–69CrossRefGoogle Scholar
  56. 56.
    Ross R (1992) The pathogenesis of atherosclerosis: In: Heart Disease. A textbook of cardiovascular medicine. Braunwald E (ed) WB Saunders, pp 1106–1124Google Scholar
  57. 57.
    Schwartz CJ, Valente AJ, Sprague EA, Kelley JL, Cayatte AJ, Rozek MM (1992) Pathogenesis of the atherosclerotic lesion. Implications for diabetes mellitus. Diab Care 15: 1156–1167CrossRefGoogle Scholar
  58. 58.
    Scientific Steering Committee on behalf of the Simon Broome Register Group (1991) Risk of fatal coronary heart disease in familial hypercholesterolaemia. Br Med J 303: 893–896CrossRefGoogle Scholar
  59. 59.
    Soria LF, Ludwig EH, Clarke HRG, Vega GL, Grundy SM, McCarthy BJ (1989) Association between a specific apolipoprotein B mutation and familial defective apolipoprotein B-100. Proc Natl Acad Sci USA 86: 587–591PubMedCrossRefGoogle Scholar
  60. 60.
    Stamler J, Wentworth D, Neaton JD (1986) Is relationship between serum cholesterol and risk of premature death from coronary heart disease continous and graded? Findings in 356222 primary screenees of the multiple risk factor intervention trial (MRFIT). JAMA 256: 2823–2828PubMedCrossRefGoogle Scholar
  61. 61.
    Stason WB (1990) Costs and benefits of risk factor reduction for coronary heart disease: insights from screening and treatment of cholesterol. Am Heart J 119: 718–724PubMedCrossRefGoogle Scholar
  62. 62.
    Steinberg D, Parthasarathy S, CarewT, Khoo JC, Witztum JL (1989) Beyond cholesterol. Modifications of low density lipoprotein that increase its atherogenicity. N Engl J Med 320: 915–924Google Scholar
  63. 63.
    Study Group, European Atherosclerosis Society (1987) Strategies for the prevention of coronary heart disease: a policy statement of the European Atherosclerosis Society. Eur Heart J 8: 77–88Google Scholar
  64. 64.
    Study Group, European Atherosclerosis Society (1988) Recognition and treatment of hyperlipidemia in adults: a policy statement of the European Atherosclerosis Society. Eur Heart J 9: 571–600Google Scholar
  65. 65.
    Summary of the presentation to the Canadian Consensus Conference on Cholesterol, March 9–10, 1988, Ottawa, Canada. (1988) Paper 10: Logan A. The Conclusions of the Canadian Task Force on the Periodic Health Examination: hypercholesterolemiaGoogle Scholar
  66. 66.
    Tsevat J, Weinstein MC, Williams LW, Tosteson AN, Goldman L (1991) Expected gains in life expectancy from various coronary heart disease risk factor modifications. Circulation 83: 1194–1201PubMedGoogle Scholar
  67. 67.
    Turpeinen O (1979) Effect of cholesterol-lowering diet on mortality from coronary heart disease and other causes. Circulation 59: 1–7PubMedGoogle Scholar
  68. 68.
    Utermann G (1989) The mysteries of lipoprotein (a). Science 246: 904–910PubMedCrossRefGoogle Scholar
  69. 69.
    Williams RR, Hunt SC, Wu LL, Hopkins PN, Hasstedt SJ, Schumacher MC, Stults BM, Kuida H (1990) Concordant dyslipidemia, hypertension and early coronary disease in Utah families. Klin Wochenschr 68 suppl XX: 53–59Google Scholar

Copyright information

© Dr. Dietrich Steinkopff Verlag GmbH & Co. KG, Darmstadt 1994

Authors and Affiliations

  • G. Schmitz
    • 1
  • K. J. Lackner
  1. 1.Institut für Klinische Chemie und LaboratoriumsmedizinUniversität RegensburgRegensburgGermany

Personalised recommendations