The effect of salsalate therapy on endothelial function in a broad range of subjects.

Inflammation is fundamental to the development of atherosclerosis. we examined the effect of anti-inflammatory doses of salicylate on endothelium-dependent vasodilation,a biomarker of cardiovascular risk,in a broad range of subjects. we performed a randomized,double-blind,placebo-controlled crossover trial evaluating the effects of 4 weeks of high-dose salsalate (disalicylate) therapy on endothelium-dependent flow-mediated and endothelium-independent vasodilation. fifty-eight subjects,including 17 with metabolic syndrome,13 with atherosclerosis,and 28 healthy controls,were studied. among all subjects,endothelium-dependent flow-mediated vasodilation decreased after salsalate compared with placebo therapy (p=0.01),whereas nitroglycerin-mediated,endothelium-independent vasodilation was unchanged (p=0.97). endothelium-dependent flow-mediated vasodilation after salsalate therapy was impaired compared with placebo therapy in subjects with therapeutic salicylate levels (n=31,p<0.02) but not in subjects with subtherapeutic levels (p>0.2). salsalate therapy,particularly when therapeutic salicylate levels are achieved,impairs endothelium-dependent vasodilation in a broad range of subjects. these data raise concern about the possible deleterious effects of anti-inflammatory doses of salsalate on cardiovascular risk. www.clinicaltrials.gov. unique identifiers: nct00760019 and nct00762827.