Ineffective decrease of serum cholesterol by simvastatin in a subgroup of hypercholesterolemic coronary patients.
We measured serum cholesterol concentrations and synthesis markers (e.g. serum lathosterol to cholesterol ratio), and absorption markers (e.g. serum campesterol to cholesterol ratio) of cholesterol in 319 good responders (GR; dose 20 mg up to 1 year) and in 115 poor responders (PR; dose increased at 6 weeks to 40 mg) among Finnish participants in the Scandinavian Simvastatin Survival Study at baseline, 6 weeks and 1 year of the simvastatin treatment. The baseline cholesterol level and the ratios of the absorption markers were higher and those of the synthesis markers lower in PR than GR. The ratios of the precursor sterols were negatively related to the baseline cholesterol in GR only (P=0.003). The cholesterol levels, and the ratios of the precursor sterols were decreased and those of the absorption marker sterols increased less consistently in PR than GR by 20 mg, the group differences being only slightly lessened by the dose addition to 40 mg. One-year differences were still frequently significant. The baseline cholesterol concentrations were negatively related to the reduction of the precursor sterol ratios in GR, the change of cholesterol being positively related to those of the synthesis markers and negatively to those of the absorption markers only in PR. Thus, patients needing large statin dose for cholesterol normalization have high absorption and low synthesis of cholesterol, yet baseline synthesis is inversely related to cholesterol level only in GR. The synthesis rate is less markedly reduced by the large than by the small statin dose in the PR, and the reduction is related, in contrast to that in the GR, to lowering of cholesterol.
Department of Medicine, Division of Internal Medicine, University of Helsinki, P.O. Box 340, FIN-00029 HUS, Helsinki, Finland. tatu.a.miettinen@helsinki.fi
Tatu A
TA
Miettinen
Helena
H
Gylling
D004083:Cholestanol / Q000097:blood; D002784:Cholesterol / Q000097:blood*; D003897:Desmosterol / Q000097:blood; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D019821:Simvastatin / Q000008:administration & dosage* / Q000627:therapeutic use; D012855:Sitosterols / Q000097:blood
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012855:Sitosterols; D003897:Desmosterol; C001521:lathosterol; D004083:Cholestanol; D002784:Cholesterol; D019821:Simvastatin