Different effects of commonly prescribed statins on abdominal aortic aneurysm wall biology

Eur J Vasc Endovasc Surg. 2010 May;39(5):569-76. doi: 10.1016/j.ejvs.2010.01.030. Epub 2010 Mar 11.

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 1beta,2,4,5,6,8,10,12, interferon-gamma (IFNgamma), tumour necrosis factor (TNF)alpha,beta, 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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • 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
  • Biomarkers / analysis
  • Cathepsin A / analysis
  • Cathepsin B / analysis
  • 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 Metalloproteinase 2 / analysis
  • Matrix Metalloproteinase 9 / analysis
  • Middle Aged
  • Netherlands
  • Pravastatin / therapeutic use
  • Pyrroles / therapeutic use
  • Risk Assessment
  • Risk Factors
  • Simvastatin / therapeutic use
  • Tumor Necrosis Factor-alpha / analysis
  • Vascular Surgical Procedures

Substances

  • Biomarkers
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Interleukins
  • Lymphotoxin-alpha
  • Pyrroles
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Atorvastatin
  • Simvastatin
  • CTSA protein, human
  • Cathepsin A
  • CTSB protein, human
  • Cathepsin B
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Pravastatin