Time-dependent lipid response on fluvastatin therapy of patients with hypercholesterolemia sensitive to apoE phenotype.
Sixty-seven male patients with hypercholesterolemia, divided into three groups according to apolipoprotein E phenotype (33 with apoE3/ 3 phenotype, E3 group; 23 with 2/2 or 2/3, E2+ group; 11 with 4/4 or 4/3, E4+ group), received daily 20-40 mg of fluvastatin for 12 weeks. The levels of triglyceride (TG), cholesterol (Chol), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured after 0, 4, 8 and 12 weeks on fluvastatin and after 4 weeks washout period. Lipid percentage changes (delta) were not associated with apoE phenotype for any treatment time. Cholesterol decreased by 14% after 12 weeks and HDL-C increased by 14-16% after 12 weeks for three phenotype groups. deltaTG, deltaChol, deltaLDL-C were associated positively, while negatively for deltaHDL-C, with the corresponding basal lipid values for the three groups. The positive deltaTG values occurred at a low basal TG0 level and became negative at TG0 > 1.6-1.9 mM. For E3 and E4+ groups, only a single parameter contributed significantly into a variation of lipid percentage changes. For the E2+ group, TG0 and Chol0 contributed in a reciprocal manner into deltaTG12/0, both positively into deltaChol8/0; Chol0 and HDL-C0 both negatively contributed into deltaHDL-C12/0. HDL-C0 contributed reciprocally into LDL-C variability for E2+ and E4+ groups. Three effects seem to contribute differently into lipid response among patients with different apoE phenotype: the inhibition of hepatic and lipoprotein lipase activities, the competition between TG-rich and low-density lipoproteins for LDL-receptor and the accumulation of intermediate-density lipoproteins in patients bearing E2 isoform.
Dergunov
Alexander D
AD
National Research Centre for Preventive Medicine, 10, Petroverigsky Street, 101953 Moscow, Russia. dergunov@img.ras.ru
Perova
Natalya V
NV
Visvikis
Sophie
S
Siest
Gerard
G
D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001057:Apolipoproteins E / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use*; D000077340:Fluvastatin; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy; D007211:Indoles / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood*; D010641:Phenotype; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D008055:Lipids; D014280:Triglycerides; D000077340:Fluvastatin