Effect of sulfasalazine on inflammation and endothelial function in patients with established coronary artery disease

• Published in: Vascular medicine (London, England) Vol. 17; no. 2; pp. 101 - 107
• Main Authors: Tabit, Corey E, Holbrook, Monica, Shenouda, Sherene M, Dohadwala, Mustali M, Widlansky, Michael E, Frame, Alissa A, Kim, Brian H, Duess, Mai-Ann, Kluge, Matthew A, Levit, Aaron, Keaney, John F, Vita, Joseph A, Hamburg, Naomi M
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.04.2012; Arnold; Sage Publications Ltd
• Subjects: Aged; Analysis of Variance; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Biological and medical sciences; Biomarkers - blood; Blood and lymphatic vessels; Boston; Brachial Artery - diagnostic imaging; Brachial Artery - drug effects; Brachial Artery - immunology; Brachial Artery - physiopathology; Cardiology. Vascular system; Coronary Artery Disease - blood; Coronary Artery Disease - drug therapy; Coronary Artery Disease - immunology; Coronary Artery Disease - physiopathology; Coronary heart disease; Cross-Over Studies; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Double-Blind Method; Endothelium, Vascular - diagnostic imaging; Endothelium, Vascular - drug effects; Endothelium, Vascular - immunology; Endothelium, Vascular - physiopathology; Female; Fingers - blood supply; Heart; Humans; Inflammation Mediators - blood; Leukocytes - drug effects; Leukocytes - immunology; Male; Manometry; Medical sciences; Middle Aged; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; Predictive Value of Tests; Sulfasalazine - adverse effects; Sulfasalazine - therapeutic use; Time Factors; Treatment Outcome; Ultrasonography, Doppler; Vasodilation - drug effects; coronary artery disease; endothelial function; inflammation; vascular; Human; Sulfonamides; Antiinflammatory agent; Cardiovascular disease; Sulfasalazine; Inflammation; Salicylates; Coronary heart disease
• ISSN: 1358-863X; 1477-0377; 1477-0377
• DOI: 10.1177/1358863X12440117

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.