Different Effects of Commonly Prescribed Statins on Abdominal Aortic Aneurysm Wall Biology

Abstract Background Pharmaceutical stabilisation of the abdominal aortic aneurysm (AAA) wall can delay surgery and improve outcome. Observational studies indicate statins can be used to reduce AAA growth but mechanistic data are scarce. In this study, our aim was to determine the pleiotropic effects...

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Published in:	European journal of vascular and endovascular surgery 2010-05, Vol.39 (5), p.569-576
Main Authors:	Hurks, R, Hoefer, I.E, Vink, A, Pasterkamp, G, Schoneveld, A, Kerver, M, de Vries, J.-P.P.M, Tangelder, M.J, Moll, F.L
Format:	Article
Language:	eng
Subjects:	Abdominal aortic aneurysm Aged Aneurysm Aorta - chemistry Aorta - drug effects Aorta - pathology Aorta - surgery Aortic Aneurysm, Abdominal - drug therapy Aortic Aneurysm, Abdominal - metabolism Aortic Aneurysm, Abdominal - pathology Aortic Aneurysm, Abdominal - surgery Atorvastatin Calcium Biomarkers - analysis Cathepsin A - analysis Cathepsin B - analysis Cathepsins Chi-Square Distribution Cohort Studies Disease Progression Female Heptanoic Acids - therapeutic use Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use Interferon-gamma - analysis Interleukins - analysis Lymphotoxin-alpha - analysis Male Matrix metalloproteases Matrix Metalloproteinase 2 - analysis Matrix Metalloproteinase 9 - analysis Middle Aged Netherlands Pleiotropic effects Pravastatin - therapeutic use Pyrroles - therapeutic use Risk Assessment Risk Factors Simvastatin - therapeutic use Statins Surgery Tumor Necrosis Factor-alpha - analysis Vascular Surgical Procedures
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Summary:	Abstract Background Pharmaceutical stabilisation of the abdominal aortic aneurysm (AAA) wall can delay surgery and improve outcome. Observational studies indicate statins can be used to reduce AAA growth but mechanistic data are scarce. In this study, our aim was to determine the pleiotropic effects of different statins on AAA wall composition. Methods We included 216 patients undergoing open AAA repair, of which 60 used simvastatin, 52 atorvastatin and 23 pravastatin. The AAA wall histology and protein expression (IL 1β,2,4,5,6,8,10,12, interferon-gamma (IFNγ), tumour necrosis factor (TNF)α,β, matrix metalloproteinase (MMP)2 and 9 activities, total MMP8,9 and cathepsin A and B levels) between statin users and non-users were compared as also among the use of different statins. Results As far as histological inflammation goes, the AAA walls of statin users did not differ from those not using them. After multivariate adjustment for risk factors, pravastatin use was associated with tendencies of increased MMP8 ( p = 0.022), active MMP9 ( p = 0.040) and higher cathepsin B ( p = 0.056) levels. The AAA walls of simvastatin and atorvastatin users showed no differences in proteases or cytokines in multivariate analyses. Conclusions The use of statins was not associated with a decrease in protease levels or inflammation. The trends of elevated protease levels associated with pravastatin use suggest pleiotropic differences among the various statins, supporting the need for further research to target pharmaceutical AAA treatment.
ISSN:	1078-5884 1532-2165