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document
Effect of sulfasalazine on inflammation and endothelial function in patients with established coronary artery disease . Inflammation is critical for atherosclerosis development and may be a target for risk-reduction therapy . In experimental studies , activation of the inflammatory regulator , nuclear factor kappa B ( NFlB ) , contributes to endothelial activation and reduced nitric oxide production . We treated patients with coronary artery disease with sulfasalazine , an inhibitor of NFκB , and placebo in a randomized , double-blind , crossover study design . Brachial artery flow-mediated dilation ( FMD ) and digital vascular function were measured at baseline and after each 6-week treatment period . Of the 53 patients enrolled in the crossover study , 32 ( age 60 ± 10 , 22 % female ) completed all the visits , with a high rate of study withdrawal due to gastrointestinal side effects . In a subset of 10 participants , we compared the effects of 4 days of sulfasalazine treatment ( n = 5 ) to no treatment ( n = 5 ) on NFκB-regulated gene expression in peripheral blood mononuclear cells . Tumor necrosis factor α-stimulated expression of CD69 and NFlB subunit p50 was significantly blunted after 4 days of sulfasalazine treatment but not after no treatment . However , FMD and digital vasodilator response did not significantly change from baseline with long-term sulfasalazine treatment . Short-term sulfasalazine inhibited NFlB activity ; however , long-term treatment was poorly tolerated and did not improve endothelial function . Our findings suggest that sulfasalazine therapy is not the optimal anti-inflammatory treatment for reversing endothelial dysfunction in cardiovascular disease . Further studies are warranted to investigate the potential for NFlB inhibition to reduce cardiovascular risk .
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Intervention_Pharmacological
sulfasalazine
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Outcome_Physical
inflammation and endothelial function
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Participant_Condition
patients with established coronary artery disease .