In vivo confirmation of the role of statins in reducing nitric oxide and C-reactive protein levels in peripheral arterial disease

Abstract

Objectives: Inflammatory and other processes mediating impairment of endothelial function, where there are increased levels of C-reactive protein (CRP) and plasma nitrites, have a part to play in the early stages of peripheral arterial disease (PAD). Our objective was to analyse the effect of statins on the plasma nitrite and CRP levels in PAD.

Material and methods: A prospective study of 30 patients with PAD Fontaine stage II, with no prior treatment with statins, determined high sensitivity (hs)-CRP and lipid profile in the patients. Plasma nitrite levels were determined by colorimetric assay based on the Griess reaction, at baseline and after 1 month of treatment with atorvastatin 40 mg day(-1).

Results: A significant reduction in plasma nitrite levels was detected after the treatment with statins (11.88+/-7.8 microM vs. 5.7+/-1.8 microM, p=0.0001). There was also a significant reduction in hs-CRP levels (13.58+/-24.00 vs. 3.93+/-3.19, p=0.02). When the patients were stratified according to claudication stage, a significant reduction in nitrite levels was obtained, both in patients with PAD Fontaine stage IIA (9.5+/-3.3 microM vs. 5.3+/-1.7 microM, p=0.0001) and in stage IIB (16.6+/-11.6 microM vs. 6.7+/-1.8 microM, p=0.032).

Conclusions: Treatment with statins lowers plasma nitrite and CRP levels in patients with PAD. Our data support the effects of statins in vivo that have been demonstrated on the endothelium ex vivo, suggesting a beneficial effect by acting on the initial processes that trigger the disease, reducing oxidative stress (increase in the bioavailability of nitric oxide as peroxynitrite levels decrease) and curtailing the inflammatory processes which perpetuate the disease.