Baseline levels of low-density lipoprotein cholesterol and lipoprotein (a) and the AvaII polymorphism of the low-density lipoprotein receptor gene influence the response of low-density lipoprotein cholesterol to pravastatin treatment.
To investigate some individual and genetic factors that may influence the response of low-density lipoprotein cholesterol (LDL-C) to pravastatin treatment, we recruited 440 subjects with hypercholesterolemia (mean age, 57 years; 43% men) from 21 primary health care centers-outpatient clinics into a prospective, multicentered intervention trial. Pravastatin (20 mg/d) was prescribed for 16 weeks. The main outcome was the percentage variation in LDL-C concentration relative to baseline. Blood analyses and genotyping were performed centrally. The results indicated that LDL-C decreased by 20.5% (range, +21% to -66%) after pravastatin treatment. Baseline concentration of LDL-C (the higher the concentration, the greater the decrease), lipoprotein (a) levels (the lower the concentration, the greater the response), and Ava II polymorphism of the LDL-receptor gene significantly influenced the hypolipemic effect ( P < .001, P = .014, and P = .004, respectively). These 3 factors combined explained 10.6% of the variation in LDL-C response. Age, sex, smoking habit, alcohol consumption, body mass index, and apolipoprotein E genotype had no significant effect on response. We conclude that baseline levels of LDL-C and lipoprotein (a) together with the Ava II polymorphism of the LDL-receptor gene have a significant influence on the LDL-C response to pravastatin treatment in patients monitored in a standard primary health care outpatient clinic setting.
Lahoz
Carlos
C
Unidad de Arteriosclerosis, Hospital Carlos III, 28029 Madrid, Spain. clahoz.hciii@salud.madrid.org
Peña
Rocío
R
Mostaza
Jose M
JM
Laguna
Fernando
F
García-Iglesias
María F
MF
Taboada
Manuel
M
Pintó
Xavier
X
D000328:Adult; D000368:Aged; D008078:Cholesterol, LDL / Q000097:blood*; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D017270:Lipoprotein(a) / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017035:Pravastatin / Q000627:therapeutic use*; D011446:Prospective Studies; D011973:Receptors, LDL / Q000235:genetics*
D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017270:Lipoprotein(a); D011973:Receptors, LDL; D015252:Deoxyribonucleases, Type II Site-Specific; C038308:GGWCC-specific type II deoxyribonucleases; D017035:Pravastatin