title: The effect of atorvastatin on serum lipids and lipoproteins in patients with homozyous familial hypercholesterolemia undergoing LDL-apheresis therapy.
abstract: The efficacy of atorvastatin, a new hydroxymethylglutaryl (HMG)-CoA reductase inhibitor, in reducing serum lipid levels, modifying lipoprotein composition, and suppressing cholesterol synthesis was evaluated in patients with homozygous familial hypercholesterolemia (homozygous FH) undergoing LDL-apheresis therapy. Atorvastatin was given in escalating doses (10, 20, and 40 mg/day) to nine patients with homozygous FH. Five of nine patients responded well to atorvastatin; four of these patients were receptor-defective and the remaining one was receptor-negative. The change in LDL-cholesterol in the receptor-defective patients averaged -20.6% compared to the baseline level at the highest dose of atorvastatin. Of five receptor-negative type patients, only one showed good response to atorvastatin therapy with a LDL-cholesterol reduction of 14.9%. Although the other four receptor-negative patients did not show a change in LDL-cholesterol, all of them exhibited a considerable increase in HDL-cholesterol. All patients showed reduced urinary excretion of mevalonic acid, suggesting that atorvastatin decreases LDL-cholesterol by inhibiting cholesterol biosynthesis even where LDL-receptor activity is not present. Atorvastatin also decreased serum triglycerides in both receptor-negative and defective patients, especially in the latter. As cholesterol level rebounds quickly after each apheresis procedure, a combination therapy using atorvastatin and apheresis may increase the efficacy of the apheresis treatment, improving cost-benefit effectiveness by reducing the frequency of the apheresis treatment.
authors.affiliation: National Cardiovascular Centre Researh Institute, Suita, Osaka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Yamamoto
authors.forename: M
authors.initials: M
authors.lastname: Harada-Shiba
authors.forename: A
authors.initials: A
authors.lastname: Kawaguchi
authors.forename: K
authors.initials: K
authors.lastname: Oi
authors.forename: H
authors.initials: H
authors.lastname: Kubo
authors.forename: S
authors.initials: S
authors.lastname: Sakai
authors.forename: Y
authors.initials: Y
authors.lastname: Mikami
authors.forename: T
authors.initials: T
authors.lastname: Imai
authors.forename: T
authors.initials: T
authors.lastname: Ito
authors.forename: H
authors.initials: H
authors.lastname: Kato
authors.forename: M
authors.initials: M
authors.lastname: Endo
authors.forename: I
authors.initials: I
authors.lastname: Sato
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: H
authors.initials: H
authors.lastname: Hori
mesh_terms: D000293:Adolescent; D000328:Adult; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001053:Apolipoproteins / Q000097:blood; D000069059:Atorvastatin; D001781:Blood Component Removal; D005260:Female; D006538:Heptanoic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D006720:Homozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000235:genetics / Q000628:therapy*; D008055:Lipids / Q000097:blood*; D017270:Lipoprotein(a) / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood*; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008798:Mevalonic Acid / Q000652:urine; D008875:Middle Aged; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D011973:Receptors, LDL / Q000378:metabolism
chemical_list: D000924:Anticholesteremic Agents; D001053:Apolipoproteins; D006538:Heptanoic Acids; D008055:Lipids; D017270:Lipoprotein(a); D008074:Lipoproteins; D008077:Lipoproteins, LDL; D011758:Pyrroles; D011973:Receptors, LDL; D000069059:Atorvastatin; D008798:Mevalonic Acid