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Atorvastatin Decreases Apolipoprotein C-III in Apolipoprotein B-Containing Lipoprotein and HDL in Type 2 Diabetes

A potential mechanism to lower plasma triglycerides

¹ Department of Internal Medicine, University Medical Center Utrecht, Utrecht, the Netherlands
² Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands
³ Department of Biochemistry, Erasmus Medical Center, Rotterdam, the Netherlands
⁴ Department of Clinical Chemistry, Erasmus Medical Center, Rotterdam, the Netherlands

Address correspondence and reprint requests to Dr. G.M. Dallinga-Thie, Laboratory of Vascular Medicine and Metabolism, Room Bd 277, Department of Internal Medicine, Erasmus MC, Dr Molewaterplein 40, 3015 GD Rotterdam, P.O. Box 2040, 3000CA Rotterdam, Netherlands. E-mail: g.dallinga{at}erasmusmc.nl

OBJECTIVE—Apolipoprotein (apo)C-III is a constituent of HDL (HDL apoC-III) and of apoB-containing lipoproteins (LpB:C-III). It slows the clearance of triglyceride-rich lipoproteins (TRLs) by inhibition of the activity of the enzyme lipoprotein lipase (LPL) and by interference with lipoprotein binding to cell-surface receptors. Elevated plasma LpB:C-III is an independent risk factor for cardiovascular disease. We studied the effect of atorvastatin on plasma LpB:C-III and HDL apoC-III.

RESEARCH DESIGN AND METHODS—We studied the effect of 30 weeks’ treatment with 10 and 80 mg atorvastatin on plasma apoC-III levels in a randomized, double-blind, placebo-controlled trial involving 217 patients with type 2 diabetes and fasting plasma triglycerides between 1.5 and 6.0 mmol/l.

RESULTS—Baseline levels of total plasma apoC-III, HDL apoC-III, and LpB:C-III were 41.5 ± 10.0, 17.7 ± 5.5, and 23.8 ± 7.7 mg/l, respectively. Plasma apoC-III was strongly correlated with plasma triglycerides (r = 0.74, P < 0.001). Atorvastatin 10- and 80-mg treatment significantly decreased plasma apoC-III (atorvastatin 10 mg, 21%, and 80 mg, 27%), HDL apoC-III (atorvastatin 10 mg, 22%, and 80 mg, 28%) and LpB:C-III (atorvastatin 10 mg, 23%, and 80 mg, 28%; all P < 0.001). The decrease in plasma apoC-III, mainly in LpB:C-III, strongly correlated with a decrease in triglycerides (atorvastatin 10 mg, r = 0.70, and 80 mg, r = 0.78; P < 0.001). Atorvastatin treatment also leads to a reduction in the HDL apoC-III-to-HDL cholesterol and HDL apoC-III-to-apoA-I ratios, indicating a change in the number of apoC-III per HDL particle (atorvastatin 10 mg, –21%, and 80 mg, –31%; P < 0.001).

CONCLUSIONS—Atorvastatin treatment resulted in a significant dose-dependent reduction in plasma apoC-III, HDL apoC-III, and LpB:C-III levels in patients with type 2 diabetes. These data indicate a potentially important antiatherogenic effect of statin treatment and may explain (part of) the triglyceride-lowering effect of atorvastatin.

Abbreviations: apo, apolipoprotein • CVD, cardiovascular disease • DALI, Diabetes Atorvastatin Lipid Intervention • HDL apoC-III, apoC-III in HDL • LpB:C-III, apoC-III in apoB-containing lipoprotein • LPL, lipoprotein lipase • TRL, triglyceride-rich lipoprotein

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