Fluvastatin slow-release lowers platelet-activating factor acetyl hydrolase activity: a placebo-controlled trial in patients with type 2 diabetes.
Fluvastatin reduces atherogenic dense low-density lipoprotein (dLDL) in patients with type 2 diabetes mellitus (T2DM). dLDLs are associated with platelet-activating factor acetyl hydrolase (PAF-AH), an enzyme involved in inflammation and related to coronary artery disease (CAD). The association of preexisting CAD and PAF-AH and the effect of fluvastatin on enzyme activity is investigated in a placebo-controlled trial in patients with T2DM. A multicenter, double-blind, randomized comparison of fluvastatin XL (80 mg) (n = 42) and placebo (n = 47), each given once-daily for 8 wk, in 89 patients with T2DM, was conducted. At baseline and on treatment, lipoproteins, including lipoprotein (a) [Lp(a)] and LDL subfractions, and the activity of PAF-AH were measured. Increasing PAF-AH activity was significantly associated with a positive history of CAD (+0.7% per IU/liter PAH-AH; P = 0.010), the odds ratio estimate adjusted for age, gender, and body mass index of the highest quartile being 10.6 (P = 0.036). At baseline and at study end, PAF-AH activity was associated with the apolipoprotein B (apoB) content in dLDL (LDL-5 and LDL-6) (r = 0.447; P < 0.001 and r = 0.651; P < 0.001, respectively) and with non-HDL cholesterol at baseline (r = 0.485; P < 0.001). However, after additional adjustment for apoB in dLDL and non-HDL cholesterol at baseline, the odds ratio increment for CAD across PAF-AH quartiles was 2.09 (95% confidence interval, 1.02-4.29; P = 0.043). Fluvastatin treatment decreased the activity of PAF-AH by 22.8% compared with an increase of 0.4% in the placebo group (P < 0.001). This effect was independent of changes of Lp(a) concentrations. In patients with T2DM, PAF-AH activity is associated with a positive history of CAD. Fluvastatin not only decreases atherogenic dLDL but also PAF-AH activity, emphasizing the significance of fluvastatin treatment in T2DM. The antiatherogenic potential of fluvastatin in T2DM may thus be greater than expected from its effects on LDL-C and triglycerides alone.
Winkler
Karl
K
Division of Clinical Chemistry, Department of Medicine, Albert Ludwigs-University, D-79106 Freiburg, Germany. kwinkler@ukl.uni-freiburg.de
Abletshauser
Claudia
C
Friedrich
Isolde
I
Hoffmann
Michael M
MM
Wieland
Heinrich
H
März
Winfried
W
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism*; D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D001055:Apolipoproteins B / Q000097:blood; D002784:Cholesterol / Q000097:blood; D003692:Delayed-Action Preparations; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage*; D005260:Female; D000077340:Fluvastatin; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010919:Placebos
D000924:Anticholesteremic Agents; D001055:Apolipoproteins B; D003692:Delayed-Action Preparations; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D010919:Placebos; D000077340:Fluvastatin; D002784:Cholesterol; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase