Different effects of commonly prescribed statins on abdominal aortic aneurysm wall biology.
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.
Department of Vascular Surgery, University Medical Center Utrecht, Utrecht, The Netherlands. r.hurks@umcutrecht.nl
R
R
Hurks
I E
IE
Hoefer
A
A
Vink
G
G
Pasterkamp
A
A
Schoneveld
M
M
Kerver
J-P P M
JP
de Vries
M J
MJ
Tangelder
F L
FL
Moll
D000368:Aged; D001011:Aorta / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology / Q000601:surgery; D017544:Aortic Aneurysm, Abdominal / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D000069059:Atorvastatin; D015415:Biomarkers / Q000032:analysis; D043402:Cathepsin A / Q000032:analysis; D002401:Cathepsin B / Q000032:analysis; D016009:Chi-Square Distribution; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000032:analysis; D007378:Interleukins / Q000032:analysis; D008233:Lymphotoxin-alpha / Q000032:analysis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D008875:Middle Aged; D009426:Netherlands; D017035:Pravastatin / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D018570:Risk Assessment; D012307:Risk Factors; D019821:Simvastatin / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014656:Vascular Surgical Procedures
D015415:Biomarkers; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007378:Interleukins; D008233:Lymphotoxin-alpha; D011758:Pyrroles; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D000069059:Atorvastatin; D019821:Simvastatin; C468629:CTSA protein, human; D043402:Cathepsin A; C533912:CTSB protein, human; D002401:Cathepsin B; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D017035:Pravastatin