title: 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.
abstract: 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.
authors.affiliation: Unidad de Arteriosclerosis, Hospital Carlos III, 28029 Madrid, Spain. clahoz.hciii@salud.madrid.org
authors.forename: Carlos
authors.initials: C
authors.lastname: Lahoz
authors.forename: Rocío
authors.initials: R
authors.lastname: Peña
authors.forename: Jose M
authors.initials: JM
authors.lastname: Mostaza
authors.forename: Fernando
authors.initials: F
authors.lastname: Laguna
authors.forename: María F
authors.initials: MF
authors.lastname: García-Iglesias
authors.forename: Manuel
authors.initials: M
authors.lastname: Taboada
authors.forename: Xavier
authors.initials: X
authors.lastname: Pintó
mesh_terms: 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*
chemical_list: 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