Effects of atorvastatin on electrophoretic characteristics of LDL particles among subjects with heterozygous familial hypercholesterolemia.
The effects of the HMG CoA reductase inhibitor atorvastatin on electrophoretic characteristics of LDL particles were evaluated in 46 patients (28 males and 18 females) with heterozygous familial hypercholesterolemia (FH) aged 20-61 carrying either a negative or a defective LDL receptor gene mutation. Following a 6 week drug-free baseline period, FH heterozygotes were treated with atorvastatin (median dose: 20 mg/day, range 10-80 mg/day)) for 6 months to maintain their plasma LDL-cholesterol concentrations between 4.0 and 5.0 mmol/l. Atorvastatin treatment significantly reduced plasma total cholesterol, LDL-cholesterol and triglyceride levels and increased plasma HDL-cholesterol. Furthermore, atorvastatin treatment significantly increased LDL peak particle diameter (LDL-PPD) by 0.5% (from 255.0+/-6.2 to 256.4+/-5.5 A, P=0.004) and reduced the absolute concentration of cholesterol among small (<255 A) and large (>260 A) LDL particles by 35% (P<0.001). Changes in LDL-PPD and plasma triglyceride levels were inversely correlated (R=-0.34; P=0.02). Stepwise multiple linear regression analyses showed that 41.6% of the variation in the LDL-PPD response to atorvastatin was attributable to the initial LDL-PPD (14.4%, P=0.003), the apo E polymorphism (12.4%, P=0.02), the nature of the LDL receptor gene mutation (9.6%, P=0.01) and change in triglyceride levels (5.2%, P=0.04). Moreover, the reduction in the cholesterol content of LDL <255 A was directly correlated with the daily dosage of atorvastatin (P=0.05). Results of the present study showed that atorvastatin alters significantly LDL heterogeneity in patients at high risk of coronary heart disease (CHD) such as FH heterozygotes. These results also suggest that genetic and metabolic factors may be important determinants of atorvastatin-induced changes of LDL particle size and distribution among FH heterozygotes.
Larivière
Mathieu
M
Lipid Research Center, CHUL Research Center, Laval University, Room S-102 2705, Laurier Blvd., Laval, Québec, Canada G1V 4G2.
Lamarche
Benoít
B
Pirro
Matteo
M
Hogue
Jean-Charles
JC
Bergeron
Jean
J
Gagné
Claude
C
Couture
Patrick
P
D000328:Adult; D000704:Analysis of Variance; D000069059:Atorvastatin; D008078:Cholesterol, LDL / Q000032:analysis* / Q000187:drug effects*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005500:Follow-Up Studies; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics; D016014:Linear Models; D008077:Lipoproteins, LDL / Q000032:analysis / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010316:Particle Size; D011336:Probability; D011446:Prospective Studies; D011758:Pyrroles / Q000008:administration & dosage*; D016896:Treatment Outcome
D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D008077:Lipoproteins, LDL; D011758:Pyrroles; D000069059:Atorvastatin