02.01 SIMVASTATIN PREVENTS ACUTE INFLAMMATION-INDUCED AORTIC STIFFENING IN HEALTHY VOLUNTEERS

S. Wallace, K. Maki-Petaja, J. Cheriyan, E. Davidson, C. McEniery, I. Wilkinson, R. Kharbanda
2006 Artery Research  
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
more » ... PWV) 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. Background: L-arginine, being the substrate for endothelial nitric oxide synthase, is essential for normal endothelial function. Endothelial dysfunction is accompanied by increased arterial stiffness. Aim of the study was to investigate in healthy smokers the effect of a short-term daily L-arginine administration on vascular function. Methods: We studied the effect of a 3-day oral administration of L-arginine in 12 healthy smokers (aged 24±3 yrs) on 3 occasions (day 0: baseline measurements, day 1 and day 3). The study was carried out on two separate arms, one with L-arginine (7 g tid) and one with placebo according to a randomized, placebo-controlled, double-blind, cross-over design. All
doi:10.1016/s1872-9312(07)70004-2 fatcat:6jripziquje3zn2waja6dan54u