Cardiovascular-kidney-metabolic health, genetic predisposition and incident risk of psoriasis.

Limited evidence exists concerning the relationship between cardiovascular-kidney-metabolic (CKM) health and the incidence and prognosis of psoriasis. This study aimed to evaluate the associations between CKM status, genetic risk and the risk of developing psoriasis, as well as to examine the impact of CKM syndrome on life expectancy in patients with psoriasis. This prospective cohort study included 392,454 participants free of psoriasis from the UK Biobank. CKM syndrome was defined by the presence of metabolic risk factors, chronic kidney disease and cardiovascular disease, categorized into five stages (0-4). The genetic risk of psoriasis was assessed using a polygenic risk score. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for the incident risk of psoriasis. Compared to participants in stage 0, the multivariable-adjusted HRs (95% CIs) for developing psoriasis in individuals with CKM stages 1, 2, 3 and 4 were 1.21 (1.06-1.38), 1.38 (1.24-1.55), 1.64 (1.42-1.91) and 1.72 (1.47-2.01), respectively. Joint association analyses revealed that participants with CKM stage 4 and high genetic risk had the highest risk of psoriasis compared to those at stage 0 with low genetic risk (HR = 2.82, 95% CI: 2.28-3.49). Notably, there was a significant positive additive interaction between advanced CKM stages and high genetic risk in the development of psoriasis (RERI = 0.82, 95% CI: 0.35-1.32). Additionally, within the psoriasis population, advanced CKM stage (stage 4) was associated with a greater reduction in life expectancy (2.03 years, 95% CI: 0.25-3.81 years). Poor CKM health was significantly associated with a higher risk of psoriasis in midlife and older adults, particularly among those with high genetic risk and was further linked to decreased life expectancy among patients with psoriasis.