SAT-066 Effect Of Interleukin-1-receptor Antagonist On Hemodynamics And Renin-angiotensin-aldosterone System In Obese Individuals

Background: Interleukin (IL)-1 antagonism led to a decrease of systolic blood pressure (5mmHg) in obese individuals. The underlying mechanism is unknown. Based on experimental data in animals we hypothesised a blood-pressure lowering effect of IL-1-antagonism via modulation of the Renin-Angiotensin-Aldosterone System (RAAS). Methods: In this post-hoc explorative study, we examined short- (2 days) and long-term effects (4 weeks) of IL-1 antagonism (anakinra/Kineret®) on RAAS-peptide-profiles and on hemodynamic parameters assessed by a non-invasive measurement using HOTMAN® system in 128 obese (BMI > 30kg/m2) individuals with at least one feature of the metabolic syndrome from two previous interventional trials (CortIL trial a prospective interventional trial (n= 61) and TestIL trial, a placebo controlled-double blinded interventional trial (n=67)). Results: Upon IL-1 antagonism circulating levels of angiotensin II, angiotensin I, aldosterone and renin remained unchanged after short- and long-term treatment, respectively. In contrast, the vasodilatory angiotensin 1-7 peptide significantly increased after 4 weeks compared to placebo (in between group difference 16.35 pmol/L [1.22 to 30.17], p=0.028), without short-term effect on day 2. Non-invasive hemodynamic measurement revealed a decrease in the stroke systemic vascular resistance index (SSVRI) with an in between group difference of -62.65 dyn.sec.cm-5.m2 [95%CI -116.94 to -18.36], p=0.008 (consistent with a 25%-decrease) after 4 weeks of treatment compared to baseline. Conclusion: IL-1 antagonism in obese individuals with features of the metabolic syndrome led to an increase of the vasodilatory angiotensin 1-7 peptide and a decrease in peripheral vascular resistance, reflected by the SSVRI after 4 weeks of treatment. These findings point to a possible blood pressure lowering mechanism via modulation of the RAAS-system of IL-1 antagonism.