Effect of chronic inflammation inhibition with salsalate on aortic stiffness and vascular endothelial function in older adults: A randomized controlled study

Abstract

Chronic activation of the proinflammatory transcription factor nuclear factor kappa-B (NFkB) is linked to age-associated vascular dysfunction. Acute inhibition of NFkB with high-dose salsalate (>4g), a non-acetylated salicylate known to block NFkB activation, improves aortic stiffness and endothelial function in aged rodents and humans.Therefore, we hypothesized that chronic salsalate therapy at the US FDA approved starting dose (3 g/day) would improve age-associated aortic stiffness and endothelial dysfunction in older adults. A total of 28 normotensive older adults (57.4 ± 1.3 yrs; 11M/13F) were randomized to salsalate 3 g/day (n = 14) or placebo (n = 14) for 4 weeks and had assessments of aortic stiffness (carotid-femoral pulse wave velocity, CFPWV) and endothelial function (brachial artery flow-mediated dilation, FMD).A group of 17 young adults (age 26 ± 1 yrs) were not randomized. As expected, baseline CFPWV was higher (8.1 ± 0.3 vs 5.3 ± 0.2 m/sec, P < 0.01) and FMD was lower (3.4 ± 0.8 vs. 5.9 ± 1.0%, P = 0.03) in the older vs. young. In the older adults, neither FMD (SALS: 3.5 ± 1.4 to 4.6 ± 1.2%; PLAC: 3.4 ± 1.2 to 2.5 ± 1.3%, ANOVA P = 0.98) nor CFPWV (SALS: 8.1 ± 0.5 to 8.4 ± 0.6 m/sec; PLAC: 7.6 ± 0.5 to 7.6 ± 0.4 m/sec, ANOVA P = 0.41) was altered after 4 weeks of salsalate vs. placebo.These data fail to demonstrate that chronic salsalate timproves age-associated aortic stiffness or endothelial dysfunction in older adults. Future studies should test longer duration therapy or more selective inflammatory inhibitors on vascular aging in humans.