Simvastatin prevents inflammation‐induced aortic stiffening and endothelial dysfunction

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.