Long-term Effect of LDL-Apheresis on Familial Hypercholesterolemia Homozygotes
LDL-apheresis is the practical way of treatment for homozygous cases of familial hypercholesterolemia (FH). Long-term observations for 2–5 years have shown that atheromatous plaques can regress in major arteries including coronary arteries by repeating LDL-apheresis once a week or every two weeks. However, the observation for much longer time revealed that atherosclerotic vascular lesions relaps or progress with the involvement of the aortic valve being the most obstinate complication. Important problem is the severe rebound of cholesterol taking place after the apheresis and it is necessary to suppress this rebound as much as possible, so that we can keep the post-apheresis LDL-cholesterol levels in or near the optimal range as long as possible. It has been thought that statins are ineffective in patients with homozygous FH because of the lack of LDL-receptors. A recent trial carried out in South Africa showed atorvastatin being capable of suppressing cholesterol synthesis and useful in reducing the rebound in patients with homozygous FH under apheresis treatment. Another clinical trial carried out in Japan also showed the efficacy of the statin in such patients, suggesting that the statin is able to decrease cholesterol by inhibiting the synthesis of cholesterol and VLDL even in the absence of up-regulation of the LDL-receptor.
KeywordsAortic Valve Aortic Regurgitation Familial Hypercholesterolemia Familial Hypercholesterolemia Atheromatous Plaque
Unable to display preview. Download preview PDF.
- 2.Bilheimer DW (1989) Portacaval shunt and liver transplantation in treatment of familial hypercholesterolemiaGoogle Scholar
- 5.DeGenne JL, Toutaine R, Maunand B, Truffert J, Laudat P (1967) Forme homozygotes cutaneo-tendineuses de Xanthomatose hypercholesterolemique dans une observation familiale exemplaire. Essai de Plasmapherese a titre de traitment heroique. Bull Mem Soc Hop Paris 118: 1377–1402.Google Scholar
- 8.Yamamoto A, Yokoyama S, Kojima S, Kawaguchi A, Bosch T (1990) Comparison of double membrane filtration and affinity chromatographic techniques. In:Lock G (ed) Apheresis, Wiley-Liss, New York, pp 613–622.Google Scholar
- 10.Takada S, Tani N, Ohnishi M, Kau A, Narisada U (1988) Automated continuus low density lipoprotein absorption system. In: Oda T (ed) Therapeutic Plasmapheresis VII, ISAO Press, Cleveland, pp 454–459.Google Scholar
- 11.Daida H, Young JL, Yokoi H, Kanoh T, Ishiwata S, Nishikawa H, Takasu F, Kato H, Kusumi Y (1994) Prevention of restenosis after percutaneous transuminal coronary angioplasty by reducing lipoprotein (a) levels with low-density lipoprotein apheresis. Am J Cardiol 73: 1037–1040.PubMedCrossRefGoogle Scholar
- 15.Kawaguchi A, Miyatake K, Yutani C, Beppu S, Tsushima M, Yamamura T, Yamamoto A (1998) Hypercholesterolemic valvulopathy: Characteristic distribution of premature atherosclerosis in homozygous and heterozygous familial hypercholesterolemia. Am Heart J (in press).Google Scholar
- 20.Borberg H (1997) Fifteen years experience with LDL-apheresis. In: Yamamoto A (ed) Therapeutic Plasmapheresis XVI Jpn Soc Apheresis, Tokyo, pp 56–62.Google Scholar
- 23.Harada-Shiba M, Yamamura T, Toyota Y, Tsushima M, Kojima S, Yamamoto A (1996) Rebound curve following LDL-apheresis reflects catabolic rate of plasma cholesterol and the synthetic rate of Lp(a). In Gotto AM Jr, Paoletti R, Smith LC, Catapano AL, Jackson AS (eds), Drugs Affecting Lipid Metabolism. Risk Factors and Future Direction,Kluwer, Dordrecht, pp 591–597.CrossRefGoogle Scholar
- 25.Nawrocki JW, Weiss SR, Davidson MH, Sprecher DL, Schwartz SL, Lupien PJ, Jones PH, Harber HE, Black DM (1995) Reduction of LDL-cholesterol by 25% to 60% in patients with primary hypercholesterolemia by atorvastatin, new HMG-CoA reductase inhibitor. Arterioscl Thromb Vascul Biol 15: 678–682.CrossRefGoogle Scholar
- 26.Bisgaier CL, Essenburg AD, Auerbach BJ, Pape ME, Sekerke CS, Gee A, Woelle S, Newton RS (1997) Attenuation of plasma low density lipoprotein cholesterol by select 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in mice devoid of low density lipoprotein receptors. J Lipid Res 38: 2502–2515.PubMedGoogle Scholar
- 28.Yamamoto A for the Japan Atorvastatin/ LDL-apheresis group (1998) The effect of atorvastatin, a new HMG-CoA reductase inhibitor, and LDL-apheresis on homozygous familial hypercholesterolemia. XIII Int Symp on Drugs Affecting Lipid Metabolism (1998) Florence, May 30-June 3, Poster No 137.Google Scholar