Simvastatin prevents inflammation-induced aortic stiffening and endothelial dysfunction

Wallace, S.M.L., Mäki-Petäjä, K.M., Cheriyan, J., Davidson, E.H., Cherry, L., McEniery, C.M., Sattar, N. , Wilkinson, I.B. and Kharbanda, R.K. (2010) Simvastatin prevents inflammation-induced aortic stiffening and endothelial dysfunction. British Journal of Clinical Pharmacology, 70(6), pp. 799-806. (doi: 10.1111/j.1365-2125.2010.03745.x)

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Both acute and chronic inflammation are associated with aortic stiffening and endothelial dysfunction. • Statins have been shown to reduce inflammation and arterial stiffening and to improve endothelial function in patients with chronic inflammation. • In a model of acute-inflammation, statins have been shown to prevent endothelial dysfunction, but the effect on aortic stiffening is unknown. WHAT THIS STUDY ADDS • This study demonstrates, for the first time, that pre-treatment with simvastatin prevents inflammation-induced aortic stiffening, as well as endothelial dysfunction, in a cohort of healthy individuals. • It also shows that simvastatin prevents the inflammation-induced reduction in concentrations of apolipoprotein A-I. AIMS The aim of this study was to determine whether simvastatin would protect against inflammation-induced aortic stiffening and endothelial dysfunction. METHODS Aortic pulse wave velocity (aPWV) and flow-mediated dilatation (FMD) were assessed three times, at baseline, after a 14 day administration of simvastatin or placebo and 8 h after Salmonella typhi vaccination in 50 healthy subjects. RESULTS Following vaccination there was a significant increase in aPWV in the placebo group (5.80 ± 0.87 vs. 6.21 ± 0.97 m s−1, 95% CI 0.19, 0.62, P= 0.002) but not the simvastatin group (5.68 ± 0.73 vs. 5.72 ± 0.74 m s−1, 95% CI −0.19, 0.27, P= 0.9; P= 0.016 for comparison). Whereas FMD response was reduced in the placebo group (6.77 ± 4.10 vs. 5.27 ± 2.88%, 95% CI −2.49, −0.52, P= 0.02) but not in the simvastatin group (7.07 ± 4.37 vs. 7.17 ± 9.94%, 95% CI −1.1, 1.3. P= 0.9, P > 0.001 for comparison). There was no difference in the systemic inflammatory response between groups following vaccination. However, there was a significant reduction in serum apolipoprotein A-I (Apo A-I) in the placebo, but not in the simvastatin, group. CONCLUSIONS Simvastatin prevents vaccination-induced aortic stiffening and endothelial dysfunction. This protective mechanism may be due to preservation of the Apo A-I lipid fraction, rather than pleiotropic anti-inflammatory effects of statins.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Sattar, Professor Naveed and Cherry, Mrs Lynne
• Authors: Wallace, S.M.L., Mäki-Petäjä, K.M., Cheriyan, J., Davidson, E.H., Cherry, L., McEniery, C.M., Sattar, N., Wilkinson, I.B., and Kharbanda, R.K.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences
• Journal Name: British Journal of Clinical Pharmacology
• ISSN: 0306-5251