Abstract 15003: A Circulating Genetic Signature in Psoriasis Associates With Future Cardiovascular Events

Introduction: Psoriasis (PsO) is an inflammatory skin disease associated with cardiovascular (CV) disease (CVD). Multiple biomarkers are proposed to enhance risk assessment in PsO, yet the overlap between biomarkers of PsO and CV risk are incompletely understood. We therefore investigated the whole blood transcriptome in PsO, and prevalence and future risk of a CV event. Methods: PsO patients (n=37), without CV disease and 11 age-, sex-matched controls underwent whole blood RNA sequencing. The upregulated genetic signature in PsO vs controls was then evaluated in CVD cohorts: Group 1) women referred for cardiac catheterization for (n=26, median age 61 [IQR; 54 - 70] years) vs without (n=41, median age 62 [IQR; 58 - 69] years) an active myocardial infarction (MI), group 2) patients with peripheral artery disease followed longitudinally for major adverse CV or limb events (MACLE; n=106, median age 66 [IQR; 60 - 72] years, 74% male, median follow-up 2.5 years). Results: In the PsO cohort, median age was 44 (IQR; 34 - 51) years, 49% male, and ACC/AHA ASCVD Risk Score of 1.0% (0.6 - 3.4) with no significant difference vs controls. The median psoriasis area and severity index score (PASI) was 4.0 (IQR 2.9 - 8.2), PsO duration 15 (IQR; 9 - 25) years, with 36% on biologic therapy. Overall, 247 genes were upregulated and 228 downregulated in PsO vs controls (Figure 1A, p<0.05), and 1,302 genes positively and 1,244 genes negatively associated with PASI (Figure 1B, p<0.05). Seventy-three genes overlapped between these two comparisons (Figure 1C); key cytokine regulators were IL-6, IL-1β, and IFN gamma (Figure 1D). In the CVD cohorts, 50 out of 73 genes (68%, group 1) significantly associated with prevalent MI, and 29 (40%, group 2) with incident MACLE (Figure 1E). Conclusions: A whole blood transcriptomic signature of PsO diagnosis and severity was associated with prevalent MI and incident MACLE. These data have implications for understanding the link between PsO, systemic inflammation, and CVD.