Control or Reversal of Atherosclerosis Through Therapy of Lipid Disorders

  • Richard J. Havel
  • John P. Kane
  • Mary J. Malloy


Until recently, experiments designed to test the hypothesis that human atherosclerotic lesions can be modified by reducing levels of “atherogenic” plasma lipoproteins have relied on indirect endpoints (cardiac death; signs or symptoms of ischemic vascular disease). Large numbers of persons must be enrolled in such trials and the hypolipidemic treatment must therefore be simple in application. Experience has shown that only small reductions of the level of cholesterol-rich lipoproteins (usually evaluated by changes in serum cholesterol) can be obtained in such studies. Furthermore, in order to achieve a requisite sample size, it has not proved feasible to limit enrollment to persons whose risk of experiencing the defined endpoint is very much higher than that of the population at large. The results of such studies have been equivocal, although in the main they provide some encouragement that intervention with diet or drugs may modify the course of atherosclerotic disease. In the next few months, the results of the most extensive such trial will be published—the Lipid Research Clinics Coronary Primary Prevention Trial1.


Achilles Tendon Familial Hypercholesterolemia Lipid Research Clinic Cholesteryl Oleate Heterozygous Familial Hypercholesterolemia 
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  1. 1.
    Arteriosclerosis: a report by the National Heart and Lung Institute Task Force on Arteriosclerosis. DREW Publication No. (NIH) 71–137, Vol. 1 (June 1971).Google Scholar
  2. 2.
    M.S. Brown, P.T. Kovanen, and J.L. Goldstein, Regulation of plasma cholesterol by lipoprotein receptors, Science 212: 628 (1981).CrossRefGoogle Scholar
  3. 3.
    R.J. Havel, Familial dysbetalipoproteinemia: New aspects of pathogenesis and diagnosis, Med. Clin. North Am. 66: 441 (1982).Google Scholar
  4. 4.
    R.W. Mahley, Atherogenic hyperlipoproteinemia. The cellular and molecular biology of plasma lipoproteins altered by dietary fat and cholesterol, Med. Clin. North Am. 66: 375 (1982).Google Scholar
  5. 5.
    J.L. Goldstein and M.S. Brown, The LDL receptor defect in familial hypercholesterolemia. Implications for pathogenesis and therapy, Med. Clin. North Am. 66: 335 (1982).Google Scholar
  6. 6.
    R.J. Havel, T. Kita, L. Kotite, J.P. Kane, R.L. Hamilton, J.L. Goldstein, and M.S. Brown, Concentration and composition of lipoproteins in blood plasma of the WHHL rabbit. An animal model of human familial hypercholesterolemia. Arteriosclerosis 2: 467 (1982).CrossRefGoogle Scholar
  7. 7.
    L.M. Buja, T. Kita, J.L. Goldstein, Y. Watanabe, and M.S. Brown, Cellular pathology of progressive atherosclerosis in the WHHL rabbit. An animal model of familial hypercholesterolemia, Arteriosclerosis 3: 87 (1983).CrossRefGoogle Scholar
  8. 8.
    C.J. Fielding and P.E. Fielding, Cholesterol transport between cells and body fluids. Role of plasma lipoproteins and the plasma cholesterol esterification system, Med. Clin. North Am. 66: 363 (1982).Google Scholar
  9. 9.
    R.J. Havel, J.L. Goldstein, and M.S. Brown, Lipoproteins and lipid transport, in: “Metabolic Control and Disease, 8th Edition,” P.K. Bondy and L.E. Rosenberg, eds., W.B. Saunders, Philadelphia (1980).Google Scholar
  10. 10.
    J.P. Kane, M.J. Malloy, P. Tun, N.R. Phillips, D.D. Freedman, M.L. Williams, J.S. Rowe, and R.J. Havel, Normalization of low-density-lipoprotein levels in heterozygous familial hypercholesterolemia with a combined drug regimen, New Engl. J. Med. 304: 251 (1981).CrossRefGoogle Scholar
  11. 11.
    R.J. Havel and J.P. Kane, Therapy of hyperlipidemic states, Annu. Rev. Med. 33: 417 (1982).CrossRefGoogle Scholar
  12. 12.
    D.H. Blankenhorn, Reversibility of latent atherosclerosis. Studies by femoral angiography in humans, Mod. Concepts Cardiovasc. Dis. 47: 79 (1978).Google Scholar
  13. 13.
    G.B. Brown, E. Bolson, M. Frimer, and H.T. Dodge, Quantitative coronary arteriography. Estimation of dimensions, hemodynamic resistance, and atheroma mass of coronary artery lesions using the arteriogram and digital computation, Circulation 55: 329 (1977).CrossRefGoogle Scholar
  14. 14.
    M.J. Malloy, B.H. Brundage, J.P. Kane, N.R. Phillips, and R.J. Havel, Relationship of diameters of xanthomatous tendons and plasma lipoprotein levels to extent of coronary atherosclerosis in familial hypercholesterolemia, Arteriosclerosis 3: 482a (1983).Google Scholar
  15. 15.
    H. Mabuchi, T. Sakai, Y. Sakai, A. Hoshimura, A. Watanabe, T. Wakasugi, J. Koizumi, and R. Takeda, Reduction of serum cholesterol in heterozygous patients with familial hypercholesterolemia. Additive effects of compactin and cholestyramine, New Engl. J. Med. 308: 609 (1983).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1984

Authors and Affiliations

  • Richard J. Havel
    • 1
  • John P. Kane
    • 1
  • Mary J. Malloy
    • 1
  1. 1.Cardiovascular Research Institute and Department of MedicineUniversity of CaliforniaSan FranciscoUSA

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