Atorvastatin Improves Postprandial Lipoprotein Metabolism in Normolipidemic Subjects

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Abstract
Atorvastatin is a potent HMG-CoA reductase inhibitor that de- creases low-density lipoprotein (LDL) cholesterol and fasting triglyc- eride concentrations. Because of the positive association between elevated postprandial lipoproteins and atherosclerosis, we investi- gated the effect of atorvastatin on postprandial lipoprotein metabo- lism. The effect of 4 weeks of atorvastatin therapy (10 mg/day) was evaluated in 10 normolipidemic men (30 6 2 yr; body mass index, 22 6 3 kg/m2; cholesterol, 4.84 6 0.54 mmol/L; triglyceride, 1.47 6 0.50 mmol/L; high-density lipoprotein cholesterol, 1.17 6 0.18 mmol/L; LDL-cholesterol, 3.00 6 0.49 mmol/L). Postprandial lipoprotein me- tabolism 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 ultracen- trifugation, and triglycerides, cholesterol, apolipoprotein B, apoB-48, and retinyl-palmitate were determined in plasma and in each li- poprotein fraction. Atorvastatin therapy significantly (P , 0.001) decreased fasting cholesterol (228%), triglycerides (230%), LDL- cholesterol (-41%), and apolipoprotein B (239%), whereas high- density lipoprotein cholesterol increased (4%, not significant). The area under the curve for plasma triglycerides (227%) and CR trig- lycerides (240%), cholesterol (249%), and apoB-48 (243%) decreased significantly (P , 0.05), whereas CR retinyl-palmitate decreased (234%) with borderline significance (P 5 0.08). However, none of the CM parameters changed with atorvastatin therapy. This indicates that, in addition to improving fasting lipoprotein concentrations, ator- vastatin 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. (J Clin Endocrinol Metab 85: 4224 - 4230, 2000)

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