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

Author(s): Nohria A(1), Kinlay S, Buck JS, Redline W, Copeland-Halperin R, Kim S, Beckman JA.

Affiliation(s): Author information: (1)Cardiovascular Medicine, Department of Internal Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Publication date & source: 2014, J Am Heart Assoc. , 3(1):e000609

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.

Page last updated: 2014-12-01

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