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

A Nohria, S Kinlay, JS Buck, W Redline… - Journal of the …, 2014 - Am Heart Assoc
A Nohria, S Kinlay, JS Buck, W Redline, R Copeland‐Halperin, S Kim, JA Beckman
Journal of the American Heart Association, 2014Am Heart Assoc
Background 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. Methods and
Results 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 …
Background
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.
Methods and Results
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).
Conclusions
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.
Clinical Trial Registration
URL: www.clinicaltrials.gov. Unique Identifiers: NCT00760019 and NCT00762827.
Am Heart Assoc