title: The effect of salsalate therapy on endothelial function in a broad range of subjects.
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.
  
  
  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.
  
  
  BACKGROUND
  www.clinicaltrials.gov. Unique Identifiers: NCT00760019 and NCT00762827.
authors.affiliation: Cardiovascular Medicine, Department of Internal Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Anju
authors.initials: A
authors.lastname: Nohria
authors.forename: Scott
authors.initials: S
authors.lastname: Kinlay
authors.forename: J Stewart
authors.initials: JS
authors.lastname: Buck
authors.forename: Whitney
authors.initials: W
authors.lastname: Redline
authors.forename: Robert
authors.initials: R
authors.lastname: Copeland-Halperin
authors.forename: Sora
authors.initials: S
authors.lastname: Kim
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Beckman
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D050197:Atherosclerosis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D001900:Boston; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D008875:Middle Aged; D012459:Salicylates / Q000009:adverse effects*; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D012459:Salicylates; D014665:Vasodilator Agents; C014182:salicylsalicylic acid
keywords: atherosclerosis; endothelium; glucose; inflammation; vasodilation