PMID- 15001601
OWN - NLM
STAT- MEDLINE
DCOM- 20040402
LR  - 20220321
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 89
IP  - 3
DP  - 2004 Mar
TI  - Fluvastatin slow-release lowers platelet-activating factor acetyl hydrolase 
      activity: a placebo-controlled trial in patients with type 2 diabetes.
PG  - 1153-9
AB  - 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.
FAU - Winkler, Karl
AU  - Winkler K
AD  - Division of Clinical Chemistry, Department of Medicine, Albert 
      Ludwigs-University, D-79106 Freiburg, Germany. kwinkler@ukl.uni-freiburg.de
FAU - Abletshauser, Claudia
AU  - Abletshauser C
FAU - Friedrich, Isolde
AU  - Friedrich I
FAU - Hoffmann, Michael M
AU  - Hoffmann MM
FAU - Wieland, Heinrich
AU  - Wieland H
FAU - Marz, Winfried
AU  - Marz W
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Anticholesteremic Agents)
RN  - 0 (Apolipoproteins B)
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Fatty Acids, Monounsaturated)
RN  - 0 (Indoles)
RN  - 0 (Placebos)
RN  - 4L066368AS (Fluvastatin)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 3.1.1.47 (1-Alkyl-2-acetylglycerophosphocholine Esterase)
SB  - IM
MH  - 1-Alkyl-2-acetylglycerophosphocholine Esterase/*metabolism
MH  - Aged
MH  - Anticholesteremic Agents/*administration & dosage
MH  - Apolipoproteins B/blood
MH  - Cholesterol/blood
MH  - Delayed-Action Preparations
MH  - Diabetes Mellitus, Type 2/*drug therapy/*metabolism
MH  - Enzyme Activation/drug effects
MH  - Fatty Acids, Monounsaturated/*administration & dosage
MH  - Female
MH  - Fluvastatin
MH  - Humans
MH  - Indoles/*administration & dosage
MH  - Male
MH  - Middle Aged
MH  - Placebos
EDAT- 2004/03/06 05:00
MHDA- 2004/04/03 05:00
CRDT- 2004/03/06 05:00
PHST- 2004/03/06 05:00 [pubmed]
PHST- 2004/04/03 05:00 [medline]
PHST- 2004/03/06 05:00 [entrez]
AID - 10.1210/jc.2003-031494 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2004 Mar;89(3):1153-9. doi: 10.1210/jc.2003-031494.