Skin Inflammation, Systemic Inflammation, and Cardiovascular Disease in Psoriasis

Importance: Psoriasis is associated with increased cardiovascular risk, but the underlying pathogenic mechanisms remain unclear. Elucidating these mechanisms can help develop treatment strategies and enhance understanding of the link between peripheral inflammation, such as psoriatic skin lesions, and cardiovascular disease (CVD). Objective: To explore whether systemic inflammation is a mediator of the association between psoriasis skin disease severity and CVD. Design, Setting, and Participants: This cohort study used data from cross-sectional study (Psoriasis Atherosclerosis and Cardiometabolic Disease Initiative [PACI]), which enrolled patients from January 2013 to February 2022, and an inception cohort study (Stockholm Psoriasis Cohort [SPC]), which enrolled patients from January 2000 to December 2005. The PACI enrolled consecutive patients referred by dermatologists in Maryland, and the SPC enrolled consecutive patients referred from a wide range of practices in Sweden. Patients with prevalent psoriasis from the PACI and patients with incident psoriasis from the SPC were included. Data were analyzed from October 2023 to January 2024. Exposures: Psoriasis skin disease severity was measured using the Psoriasis Area and Severity Index (PASI), and systemic inflammation was measured using glycan biomarker of N-acetyl side chains of acute-phase proteins (GlycA). Mediation analysis was performed by evaluating the associations between exposure, mediator, and outcome in patients with first-tertile and third-tertile PASI scores when GlycA level was set at the level observed in patients with first-tertile PASI. Main Outcomes and Measures: Noncalcified coronary burden (NCB) measured using coronary computed tomography angiography in the PACI and hospitalization for CVD or cardiovascular death in the SPC. Results: Of 260 eligible patients from the PACI, 162 (62.3%) were male, and the median (IQR) age was 51 (41-60) years; of 509 eligible patients from the SPC, 237 (46.6%) were male, and the median (IQR) age was 43 (30-57) years. In both studies, PASI was associated with GlycA level and CVD, and GlycA level was associated with CVD. The direct and indirect (through GlycA) effects of PASI on NCB were estimated at 0.94 (95% CI, 0.26-1.74) and 0.19 (95% CI, 0.02-0.47), respectively. The odds ratios for the direct and indirect effects of PASI on cardiovascular events were estimated at 1.23 (95% CI, 0.70-1.92) and 1.16 (95% CI, 1.04-1.42), respectively. Conclusions and Relevance: In this study, skin disease severity measured using PASI was associated with systemic inflammation, and both PASI and systemic inflammation, measured using GlycA levels, were associated with CVD. The association between PASI and CVD may be mediated by systemic inflammation.