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Effect of intensive plasmapheresis on the plasma cholesterol concentration with familial hypercholesterolemia

  • Carl S. Apstein
    Correspondence
    Reprint requests should be sent to: Carl S. Apstein, M.D., Director, Cardiac Muscle Research Lab, Boston University School of Medicine, 80 East Concord Street, Boston, MA 02118, U.S.A.
    Footnotes
    Affiliations
    Atherosclerosis and Clinical Research Center, Massachusetts Institute of Technology, Cambridge, MA 02118 U.S.A.
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  • Donald B. Zilversmit
    Footnotes
    Affiliations
    Atherosclerosis and Clinical Research Center, Massachusetts Institute of Technology, Cambridge, MA 02118 U.S.A.
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  • Robert S. Lees
    Affiliations
    Atherosclerosis and Clinical Research Center, Massachusetts Institute of Technology, Cambridge, MA 02118 U.S.A.
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  • P.K. George
    Affiliations
    Atherosclerosis and Clinical Research Center, Massachusetts Institute of Technology, Cambridge, MA 02118 U.S.A.
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  • Author Footnotes
    ∗ Dr. Apstein is a recipient of a Research Career Development Award from the N.I.H.
    ∗∗ Dr. Zilversmit is a Career Investigator of the American Heart Association. Present address: Cornell University, Division of Nutritional Sciences, 202 Savage Hill, Ithaca, NY 14850, U.S.A.
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      Abstract

      Plasmapheresis was studied as a means of reducing the serum cholesterol concentration in 3 hypercholesterolemic patients who each underwent courses of intensive plasmapheresis with removal of 250–500 ml of plasma each day for 5–9 days. In one homozygous Type II patient, the serum cholesterol concentration decreased from 609 ± 45 mg/100 ml (mean ± SEM) to 365 ± 17 mg/100 ml (40% decrease, P < 0.05) with two different courses of plasmapheresis. In the two other patients with non-homozygous hyperbetalipoproteinemia the serum cholesterol concentration decreased from 289 ± 27 mg/100 ml to 205 ± 19 mg/100 ml (29% decrease, p < 0.05). After cessation of treatment, the cholesterol concentration returned to pre-treatment levels in 10–13 days in the homozygous patient and 7 days in one non-homozygous hyperbetalipoproteinemic patient; clofibrate (2 g/day) in this patient was associated with a smaller reduction of the cholesterol concentration with plasmapheresis and an increased rate of return of pre-treatment levels after plasmapheresis was stopped. Sustained plasmapheresis for 6 days in the other nonhomozygous hyperbetalipoproteinemic patient resulted in a new approximate “steady state” with a serum cholesterol concentration of 176–199 mg/100 ml compared with a pre-plasmapheresis value of 227 mg/100 ml. The response of the plasma cholesterol levels to plasmapheresis was subjected to kinetic analysis based on a current model of the regulation of lipoprotein metabolism.

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      References

        • Brown M.S.
        • Goldstein J.L.
        Familial hypercholesterolemia — A genetic defect in the low-density lipoprotein receptor.
        New Engl. J. Med. 1976; 294: 1386-1390
        • Bilheimer D.W.
        • Goldstein J.L.
        • Grundy S.M.
        • et al.
        Reduction in cholesterol and low density lipoprotein synthesis after portacaval shunt surgery in a patient with homozygous familial hypercholesterolemia.
        J. Clin. Invest. 1975; 56: 1420-1430
        • Langer T.
        • Strober W.
        • Levy R.I.
        The metabolism of low density lipoprotein in familial Type II hyperlipoproteinemia.
        J. Clin. Invest. 1972; 51: 1528-1536
        • Simons L.A.D.
        • Reichl D.
        • Myant N.B.
        • et al.
        The metabolism of the apoprotein of low density lipoprotein in familial hyperbetalipoproteinemia in the homozygous form.
        Atherosclerosis. 1975; 21: 283-298
        • Goldstein J.L.
        • Brown M.S.
        Familial hypercholesterolemia — A genetic regulatory defect in cholesterol metabolism.
        Amer. J. Med. 1975; 58: 147-150
        • Apstein C.S.
        • Zilversmit D.B.
        • George P.K.
        • et al.
        Reduction of serum cholesterol with intensive plasmapheresis.
        Clin. Res. 1974; 22: 311a
        • Brown M.S.
        • Goldstein J.L.
        Receptor-mediated control of cholesterol metabolism.
        Science. 1976; 191: 150-154
        • Ahrens Jr., E.H.
        • Dole V.P.
        • Blankenhorn D.H.
        The use of orally-fed liquid formulas in metabolic studies.
        Amer. J. Clin. Nutr. 1954; 2: 336
        • Hatch F.T.
        • Lees R.S.
        Practical methods for plasma lipoprotein analysis.
        Adv. Lipid. Res. 1968; 6: 1-68
        • Berlin C.M.
        • Schmike R.T.
        Influence of turnover rates on the response of enzymes to cortisone.
        Mol. Pharmacol. 1965; 1: 149-156
        • Takeuchi N.
        • Yamamura Y.
        The effect of plasmapheresis on cholesterol synthesis in the rat — Relationship to protein synthesis.
        J. Lab. Clin. Med. 1972; 79: 801-813
        • Torsvik H.
        • Feldman H.A.
        • Fischer J.F.
        • et al.
        Effect of intravenous hyperalimentation on plasma lipoproteins in severe familial hypercholesterolemia.
        Lancet. 1975; 1: 601-604
      1. Torsvik, H., Feldman, H.A., Brook, J.G. et al., Kinetics of low-density lipoprotein metabolism in Type II hyperlipoproteinemia, Submitted for publication.

        • Turnberg L.A.
        • Mahoney M.P.
        • Gleeson M.H.
        • et al.
        Plasmapheresis and plasma exchange in the treatment of hyperlipemia and xanthomatous neuropathy in patients with primary biliary cirrhosis.
        Gut. 1972; 13: 976-981
        • DeGennes J.L.
        • Touraine R.
        • Maunand B.
        • et al.
        Formes homozygotes cutanéo-tendineuses de xanthomatose hypercholésterolémique dans une observation familiale exemplaire — Essai de plasmaphérése a titre de traitement héroique.
        Bull. Mém. Soc. Méd. Hop. Paris. 1967; 118: 1377-1402
        • Thompson G.R.
        • Lowenthal R.
        • Myant N.B.
        Plasma exchange in the management of homozygous familial hypercholesterolemia.
        Lancet. 1975; 1: 1208-1211
        • Lupien P.J.
        • Moorjani S.
        • Awad J.
        A new approach to the management of familial hypercholesterolemia — Removal of plasma cholesterol based on the principle of affinity chromatography.
        Lancet. 1976; 1: 1261-1265