Document Detail

Improvement of myocardial blood flow by lipid-lowering therapy with pravastatin is modulated by apolipoprotein E genotype.
MedLine Citation:
PMID:  17852827     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Apolipoprotein E (apoE) polymorphism affects the risk of advanced coronary artery disease, but its role in early atherosclerosis remains unknown. We used positron emission tomography (PET) to study whether coronary reactivity or its response to pravastatin is related to the apoE genotype. MATERIAL AND METHODS: Samples from 44 mildly hypercholesterolaemic men (aged 35 +/- 4 years) of an earlier trial were re-analysed according to apoE genotype. Subjects were randomized to receive either 40 mg/day pravastatin or placebo for 6 months. To assess coronary reactivity, myocardial blood flow was measured by PET at rest and during adenosine infusion. PET studies and lipid analyses were done at baseline and after 6 months of therapy. RESULTS: There were no differences between apoE epsilon3/3 and epsilon4/3 genotypes in basal or adenosine-stimulated flow or in coronary flow reserve (CFR) at baseline. There was a significant apoE genotype-by-treatment group interaction regarding the change in adenosine-stimulated flow (ANCOVA; p = 0.018) and CFR (p = 0.020) at the end of the study. In the pravastatin group, the adenosine-stimulated flow increased by 32.5 % in subjects with epsilon3/3 (n = 9), but decreased non-significantly (-14.4 %) in subjects with epsilon4/3 (n = 9) (p = 0.0009). The corresponding changes in CFR were +17.8 % for epsilon3/3 and (-11.9 % for epsilon4/3 (p = 0.05). There were no significant changes from the baseline values in placebo recipients. After pravastatin treatment, both genotype groups showed a similar decrease in serum total and low-density lipoprotein cholesterol (p<0.0001 for both). CONCLUSIONS: Coronary function improves by 6 months of pravastatin in subjects with the apoE epsilon3/3 genotype, but not in those with the epsilon4/3.
E Ilveskoski; T Lehtimäki; R Laaksonen; T Janatuinen; R Vesalainen; P Nuutila; P Laippala; P J Karhunen; J Knuuti
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Scandinavian journal of clinical and laboratory investigation     Volume:  67     ISSN:  0036-5513     ISO Abbreviation:  Scand. J. Clin. Lab. Invest.     Publication Date:  2007  
Date Detail:
Created Date:  2007-12-05     Completed Date:  2008-01-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0404375     Medline TA:  Scand J Clin Lab Invest     Country:  Norway    
Other Details:
Languages:  eng     Pagination:  723-34     Citation Subset:  IM    
Laboratory of Atherosclerosis Genetics, Centre for Laboratory Medicine, Department of Clinical Chemistry, Tampere University Hospital and Medical School, University of Tampere, Tampere, Finland.
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MeSH Terms
Adenosine / pharmacology
Analysis of Variance
Apolipoproteins E / genetics*
C-Reactive Protein / analysis
Cholesterol / blood
Cholesterol, LDL / blood
Coronary Circulation / drug effects*
Double-Blind Method
Gene Frequency
Polymorphism, Genetic*
Positron-Emission Tomography
Pravastatin / pharmacology*
Treatment Outcome
Reg. No./Substance:
0/Apolipoproteins E; 0/Cholesterol, LDL; 57-88-5/Cholesterol; 58-61-7/Adenosine; 81093-37-0/Pravastatin; 9007-41-4/C-Reactive Protein

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