Improvement of myocardial blood flow by lipid‐lowering therapy with pravastatin is modulated by apolipoprotein E genotype
| Autor: | Tuula Janatuinen, Terho Lehtimäki, Pekka J. Karhunen, Juhani Knuuti, Erkki Ilveskoski, Reijo Laaksonen, Risto Vesalainen, Pekka Laippala, Pirjo Nuutila |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Adult
Male Apolipoprotein E medicine.medical_specialty Adenosine Genotype Endothelium Clinical Biochemistry Placebo Coronary artery disease chemistry.chemical_compound Apolipoproteins E Double-Blind Method Gene Frequency Coronary Circulation Internal medicine Humans Medicine Pravastatin Analysis of Variance Polymorphism Genetic business.industry Cholesterol Coronary flow reserve Cholesterol LDL General Medicine Blood flow medicine.disease C-Reactive Protein Treatment Outcome medicine.anatomical_structure chemistry Positron-Emission Tomography Cardiology lipids (amino acids peptides and proteins) business medicine.drug |
| Zdroj: | Scandinavian Journal of Clinical and Laboratory Investigation. 67:723-734 |
| ISSN: | 1502-7686 0036-5513 |
| DOI: | 10.1080/00365510701297472 |
| Popis: | 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.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.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 (p0.0001 for both).Coronary function improves by 6 months of pravastatin in subjects with the apoE epsilon3/3 genotype, but not in those with the epsilon4/3. |
| Databáze: | OpenAIRE |
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