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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.

Original publication

DOI

10.1111/j.1365-2125.2010.03745.x

Type

Journal article

Journal

Br J Clin Pharmacol

Publication Date

12/2010

Volume

70

Pages

799 - 806

Keywords

Adult, Aorta, Aortic Diseases, Blood Flow Velocity, Double-Blind Method, Endothelium, Vascular, Female, Hemodynamics, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Inflammation, Interleukin-6, Lipids, Male, Salmonella Vaccines, Salmonella typhi, Simvastatin, Vasodilation, Young Adult