Lipid-lowering and skin vascular responses in patients with hypercholesterolaemia and peripheral arterial obstructive disease

Elevated blood cholesterol is a major risk factor for atherosclerosis. Rece nt studies show that lowering cholesterol reduces the risk of vascular dise ase, but the precise mechanisms for vascular improvement are not fully unde rstood. Furthermore, it is not known whether the beneficial effects of chol esterol lowering extend to the skin microvasculature. In this unrandomized, open design study, we used iontophoresis and laser Doppler flowmetry to ex amine forearm skin perfusion in hypercholesterolaemic patients with PAOD be fore and after cholesterol-lowering therapy with fluvastatin. Endothelium-dependent and -independent vasodilatation were measured followi ng skin iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) , respectively. Before cholesterol-lowering, vascular responses to ACh and SNP were reduced significantly in patients compared with responses in control subjects (p < 0.001 and p < 0.05, ANOVA, respectively). Fluvastatin therapy (40 mg/day) for 24 weeks significantly reduced total cholesterol (7.3 +/- 0.3 to 6.0 +/ - 0.2 mmol/l, p < 0.001) and LDL cholesterol (5.4 +/- 0.5 to 4.2 +/- 0.4 mm ol/l, p < 0.01). Vasodilatation to SNP was significantly improved at week 2 4 (p < 0.05). In patients with hypercholesterolaemia and PAOD, cholesterol-lowering with statin therapy significantly improved endothelium-independent vascular resp onses to SNP in skin microvessels. The application of the non-invasive tech niques of iontophoresis and laser Doppler flowmetry may provide useful mark ers for the assessment of microvascular function in this group of patients.