title: Atorvastatin improves postprandial lipoprotein metabolism in normolipidemlic subjects.
abstract: Atorvastatin is a potent HMG-CoA reductase inhibitor that decreases low-density lipoprotein (LDL) cholesterol and fasting triglyceride concentrations. Because of the positive association between elevated postprandial lipoproteins and atherosclerosis, we investigated the effect of atorvastatin on postprandial lipoprotein metabolism. The effect of 4 weeks of atorvastatin therapy (10 mg/day) was evaluated in 10 normolipidemic men (30+/-2 yr; body mass index, 22+/-3 kg/m2; cholesterol, 4.84+/-0.54 mmol/L; triglyceride, 1.47+/-0.50 mmol/L; high-density lipoprotein cholesterol, 1.17+/-0.18 mmol/L; LDL-cholesterol, 3.00+/-0.49 mmol/L). Postprandial lipoprotein metabolism was evaluated with a standardized fat load (1300 kcal, 87% fat, 7% carbohydrates, 6% protein, 80,000 IU vitamin A) given after 12 h fast. Plasma was obtained every 2 h for 14 h. A chylomicron (CM) and a chylomicron-remnant (CR) fraction was isolated by ultracentrifugation, and triglycerides, cholesterol, apolipoprotein B, apoB-48, and retinyl-palmitate were determined in plasma and in each lipoprotein fraction. Atorvastatin therapy significantly (P < 0.001) decreased fasting cholesterol (-28%), triglycerides (-30%), LDL-cholesterol (-41%), and apolipoprotein B (-39%), whereas high-density lipoprotein cholesterol increased (4%, not significant). The area under the curve for plasma triglycerides (-27%) and CR triglycerides (-40%), cholesterol (-49%), and apoB-48 (-43%) decreased significantly (P < 0.05), whereas CR retinyl-palmitate decreased (-34%) with borderline significance (P = 0.08). However, none of the CM parameters changed with atorvastatin therapy. This indicates that, in addition to improving fasting lipoprotein concentrations, atorvastatin improves postprandial lipoprotein metabolism presumably by increasing CR clearance or by decreasing the conversion of CMs to CRs, thus increasing the direct removal of CMs from plasma.
authors.affiliation: Department of Internal Medicine II, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany. parhofer@med2.med.uni-muenchen.de
authors.forename: K G
authors.initials: KG
authors.lastname: Parhofer
authors.forename: P H
authors.initials: PH
authors.lastname: Barrett
authors.forename: P
authors.initials: P
authors.lastname: Schwandt
mesh_terms: D000328:Adult; D000069059:Atorvastatin; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D002914:Chylomicrons / Q000097:blood; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008074:Lipoproteins / Q000097:blood* / Q000187:drug effects; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D019518:Postprandial Period / Q000502:physiology*; D011758:Pyrroles / Q000494:pharmacology*; D012016:Reference Values; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D002914:Chylomicrons; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D011758:Pyrroles; D014280:Triglycerides; D002784:Cholesterol; D000069059:Atorvastatin