Abstract 14986: A Randomized Trial of Statins to Reduce Vascular Endothelial Inflammation in Psoriasis

Introduction: Psoriasis (PsO) is a chronic skin disease associated with increased CV risk. Systemic and vascular endothelial inflammation in PsO is highly prevalent and associated with CVD. Statins reduce LDL-C, systemic inflammation, and CV events. There is minimal data supporting the use of statins in PsO. We, therefore, investigated the effect of statins on circulating and vascular endothelial biomarkers of CV risk in PsO. Methods: We performed blood RNA sequencing, targeted proteomics (n=88), and brachial vein endothelial harvesting in PsO participants (n=45, average age 45 ± 14 years, 49% male, body surface area [BSA] of PsO 8 ± 14%, Framingham Risk Score 6 ± 7%) and age- gender-matched controls (n=18). Next, PsO subjects were randomly assigned to 40 mg atorvastatin (n=15) or no-treatment (n=10). A repeat assessment occurred at week two with the primary end-point change in vascular endothelial inflammation (mean composite of LTB, CCL3, CX3CL1, CCL2, CXCL1, ICAM1, iNOS, IL-8, IL-1B, COX- 2 expression). Results: Blood RNA sequencing with pathway analysis revealed inflammasome signaling as highly upregulated in PsO compared to control with protein expression of IL-6 ( r =0.68, p <0.001) and hs-CRP ( r =0.80, p <0.001) each correlated with PsO severity (psoriasis area and severity index [PASI]). Mean vascular endothelial inflammation was also 3-fold higher ( p =0.02) in PsO compared to control and correlated with both PASI ( r =0.40, p =0.01) and LDL-C ( r =0.29, p =0.05). In PsO patients randomized to two weeks of statin therapy, LDL-C was reduced by ~50% compared to the no-treatment group (60 mg/dL vs. 111 mg/dL, p <0.001 respectively). While no decrease in inflammatory pathways at the whole blood transcriptome and protein levels were noted, vascular endothelial inflammation was 60% lower in the statin vs. no-treatment group ( p =0.02). Change in vascular endothelial inflammation correlated with change in LDL-C ( r =0.53, p <0.05) but not IL-6 ( r =-0.25, p =0.30) or hs-CRP ( r =0.15, p =0.58). Conclusions: Two-weeks of high-intensity atorvastatin reduced vascular endothelial but not systemic inflammation in PsO. These findings suggest that statins may reduce CV risk in PsO either through lipid-mediated or a direct effect of statins on the vascular endothelium.