02.01 Simvastatin Prevents Acute Inflammation-Induced Aortic Stiffening in Healthy Volunteers

Abstract

Objective

Impairment of endothelial function following typhoid vaccine can be prevented with HMG CoA reductase inhibitors (statins). Whether statins can protect against large artery stiffening is unclear. We hypothesised that an acute inflammatory stimulus (typhoid vaccine) would induce endothelial dysfunction and arterial stiffening and that pre-treatment with simvastatin would attenuate this effect.

Methods

We studied 50 healthy volunteers (mean age 26±5 years). Aortic pulse wave velocity (aPWV) was derived using sequential carotid/femoral waveform recordings. Endothelial function we assessed using flow-mediated dilatation (FMD). Following baseline readings, subjects were randomised to take 40 mg simvastatin or placebo for 14 days. Haemodynamic readings were then repeated prior to and 8 hours following intramuscular injection Salmonella typhi 0.025 mg.

Results

Treatment with simvastatin caused a –19% reduction in total cholesterol and –30% reduction in LDL (both P < 0.001). Following vaccination there was a significant increase in aPWV at 8 hours in the placebo group (5.80±0.87 vs 6.21±0.96 m/s; p = 0.002) when compared to the simvastatin group (5.74±0.72 vs 5.73±0.77 m/s; p = 0.9). There was a significant 30% reduction of FMD following vaccine in the placebo group (6.77±4.09 versus 5.20±2.83; P = 0.028). White cell count and neutrophils were significantly increased at 7hrs post vaccination in both groups (both, P < 0.05).

Conclusions

We have demonstrated that acute inflammation increases large artery stiffness, and this process can be prevented by pre-treatment with simvastatin therefore statins appear to play to vasculo-protective role against inflammatory stimuli.