title: Elevated baseline triglyceride levels modulate effects of HMGCoA reductase inhibitors on plasma lipoproteins.
abstract: BACKGROUND
  The response in levels of very-low-density (VLDL) and low-density (LDL) lipoproteins varies substantially among hyperlipidemic patients during treatment with HMGCoA reductase inhibitors. Apolipoprotein E genotype and gender are known to contribute to the regulation of steady state levels of plasma lipoproteins. This study explores the effect of these and other potential determinants of the response of VLDL and LDL to treatment with reductase inhibitors.
  
  
  METHODS
  Using mixed linear statistical models, the response of lipoprotein lipid values was studied in 142 hyperlipidemic individuals who were treated with reductase inhibitors. Patients received one or more of the following drugs individually for a total of 623 treatment observations: lovastatin, pravastatin, simvastatin, or atorvastatin. For evaluation of the effects of treatment in the aggregate, actual doses were expressed as equivalent doses of atorvastatin, using factors based on random assignment comparisons in 16 reported studies. The analysis factors considered were apolipoprotein E genotype, baseline average triglycerides >170 mg/dL (vs less), and gender.
  
  
  RESULTS
  Presence of an apo epsilon4 allele was associated with a trend toward greater reduction of triglyceride levels and a diminished ability of the reductase inhibitors to reduce LDL cholesterol levels. Gender had only minimal effect on the response of either LDL cholesterol or triglycerides. However, the effect of elevated baseline triglycerides on the response of both triglycerides and LDL cholesterol was striking and was exerted in opposite directions. The triglyceride-lowering effect of reductase inhibitors was greater in patients with initial triglyceride levels above 170 mg/dL (P=0.0001). The effect was even greater in patients with initial triglyceride levels over 250 mg/dL (P=0.015). Conversely, for LDL cholesterol levels, elevated baseline triglycerides were associated with a significantly decreased response to the drugs (P=0.0015).
  
  
  CONCLUSIONS
  These findings indicate that baseline triglyceride levels are an important predictor of response of plasma lipoproteins to HMGCoA reductase inhibitors, perhaps reflecting fundamental differences in mechanism underlying the hyperlipidemic phenotype.
authors.affiliation: Hyseq, Inc., Sunnyvale, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Drmanac
authors.forename: D C
authors.initials: DC
authors.lastname: Heilbron
authors.forename: C R
authors.initials: CR
authors.lastname: Pullinger
authors.forename: M
authors.initials: M
authors.lastname: Jafari
authors.forename: D
authors.initials: D
authors.lastname: Gietzen
authors.forename: T
authors.initials: T
authors.lastname: Ukrainczyk
authors.forename: M H
authors.initials: MH
authors.lastname: Cho
authors.forename: P H
authors.initials: PH
authors.lastname: Frost
authors.forename: K
authors.initials: K
authors.lastname: Siradze
authors.forename: R T
authors.initials: RT
authors.lastname: Drmanac
authors.forename: J P
authors.initials: JP
authors.lastname: Kane
authors.forename: M J
authors.initials: MJ
authors.lastname: Malloy
mesh_terms: D001057:Apolipoproteins E / Q000235:genetics*; D008078:Cholesterol, LDL / Q000097:blood / Q000378:metabolism*; D015243:Cholesterol, VLDL / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006949:Hyperlipidemias / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012189:Retrospective Studies; D012737:Sex Factors; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood* / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014280:Triglycerides