Endothelial Dysfunction in Psoriasis: A Comparative Analysis of Cutaneous, Inflammatory, and Metabolic Correlates

Psoriasis is associated with an elevated risk of cardiovascular disease, in which endothelial dysfunction, systemic inflammation, and insulin resistance are thought to interact. This study assessed endothelial function in 60 patients with psoriasis and 30 age- and sex-matched healthy controls, and examined its relationships with disease severity (PASI), insulin resistance (HOMA-IR), and tumor necrosis factor-α (TNF-α). Endothelial function was measured as brachial-artery flow-mediated dilation (FMD). Compared with controls, patients showed significantly reduced FMD together with higher TNF-α, HOMA-IR, renal resistive index, albumin-to-creatinine ratio, body mass index, and total cholesterol, and lower high density lipoprotein (HDL)-cholesterol (all p ≤ 0.002). Within the patient group, PASI correlated strongly and positively with TNF-α and HOMA-IR, and inversely with FMD, while both TNF-α and the renal resistive index correlated inversely with FMD (all p < 0.001). In separate multivariable regression models, a model containing TNF-α and HOMA-IR explained a slightly larger proportion of variance in FMD (R2 = 0.72) than a model containing PASI and HOMA-IR (R2 = 0.70); in both, HOMA-IR was the most consistently associated predictor, while PASI did not reach significance (standardized β = −0.18, p = 0.08). When all three predictors were entered simultaneously, strong collinearity between PASI and TNF-α (variance inflation factors 4.8 and 4.5, respectively) precluded reliable separation of their effects, and only HOMA-IR and TNF-α retained significance. These associations persisted after adjustment for age, sex, BMI, systolic blood pressure, and smoking status.These findings indicate that insulin resistance is the strongest independently associated factor of endothelial dysfunction in psoriasis, with systemic inflammation contributing additional explanatory value; however, the strong overlap between disease severity and circulating TNF-α prevents definitive separation of their individual effects, and formal mediation analyses in larger cohorts are warranted.