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Randomized Controlled Trial
. 2014 Jan 3;3(1):e000609.
doi: 10.1161/JAHA.113.000609.

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

Anju Nohria  1 , Scott Kinlay, J Stewart Buck, Whitney Redline, Robert Copeland-Halperin, Sora Kim, Joshua A Beckman
Affiliations
Randomized Controlled Trial

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

Anju Nohria et al. J Am Heart Assoc. .

Abstract

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.

Keywords: atherosclerosis; endothelium; glucose; inflammation; vasodilation.

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Figures

Figure 1.
Figure 1.
Flow‐mediated, endothelium‐dependent vasodilation of the brachial artery after placebo (P) and salsalate (S) therapy. Data shown are median (IQR). ATHERO indicates atherosclerosis; MET, metabolic syndrome.
Figure 2.
Figure 2.
Nitroglycerin‐mediated, endothelium‐independent vasodilation of the brachial artery after placebo (P) and salsalate (S) therapy. Data shown are median (IQR). ATHERO indicates atherosclerosis; MET, metabolic syndrome.
Figure 3.
Figure 3.
Flow‐mediated, endothelium‐dependent vasodilation of the brachial artery after placebo (P) and salsalate (S) therapy in subjects with a therapeutic salicylate level and those with a subtherapeutic level. Data shown are median (IQR).
See this image and copyright information in PMC

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