Atorvastatin decreases apolipoprotein C-III in apolipoprotein B-containing lipoprotein and HDL in type 2 diabetes: a potential mechanism to lower plasma triglycerides.
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.


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.
Dallinga-Thie
Geesje M
GM
Department of Internal Medicine, University Medical Center Utrecht, Utrecht, the Netherlands. g.dallinga@erasmusmc.nl
Berk-Planken
Ingrid I L
II
Bootsma
Aart H
AH
Jansen
Hans
H
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D053305:Apolipoprotein C-III; D001055:Apolipoproteins B / Q000097:blood*; D001056:Apolipoproteins C / Q000097:blood* / Q000187:drug effects; D000069059:Atorvastatin; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000517:prevention & control*; D008075:Lipoproteins, HDL / Q000097:blood* / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D053305:Apolipoprotein C-III; D001055:Apolipoproteins B; D001056:Apolipoproteins C; D006538:Heptanoic Acids; D008075:Lipoproteins, HDL; D011758:Pyrroles; D014280:Triglycerides; D000069059:Atorvastatin