Psoriasis and phenotypic age acceleration in relation to all-cause and cardiovascular disease mortality risks in US adults.

Background: Psoriasis is a chronic, immune-mediated inflammatory dermatosis associated with an elevated risk of cardiovascular disease (CVD) due to systemic inflammation and metabolic dysregulation. Phenotypic age acceleration (PhenoAge-accel) quantifies accelerated biological aging by comparing an individual's predicted 'phenotypic age' (based on immune/inflammatory markers and chronological age) to their actual age. Notably, both the onset and progression of psoriasis exhibit strong associations with biological aging process. The aim of this study was to investigate their combined effect on the risk of all-cause and CVD mortality.

Methods: This study included 11,443 participants from the National Health and Nutrition Examination Survey (NHANES) conducted during 2003-2006 and 2009-2010. Weighted multivariable logistic regression models were used to evaluate the association between PhenoAge-accel and psoriasis risk. PhenoAge-accel ≥ 0 was defined as PhenoAge-accel+. Furthermore, participants were stratified into four groups: psoriasis-/PhenoAge-accel-, psoriasis+/PhenoAge-accel-, psoriasis-/PhenoAge-accel+, and psoriasis+/PhenoAge-accel+. The Cox proportional hazards models were employed to investigate the joint effects of psoriasis and PhenoAge-accel on all-cause and CVD mortality risk.

Results: At baseline, 312 participants were diagnosed with psoriasis. After adjusting for covariates, compared to those with PhenoAge-accel < 0, the odds ratios (95% CI) for psoriasis in the PhenoAge-accel ≥ 0 group was 1.83 (1.36-2.45). During a median follow-up of 10.91 years (interquartile range: 9.83-14.75), 1059 deaths event occurred, including 306 caused by CVD. In the multivariable-adjusted model, compared with the reference group, the hazard ratios and 95% CIs for all-cause mortality in the psoriasis-/PhenoAge-accel+, psoriasis+/PhenoAge-accel-, and psoriasis+/PhenoAge-accel+ groups were 1.80 (1.54-2.10), 0.96 (0.56-1.65), and 2.70 (1.66-4.39), respectively. A similar trend was observed for CVD mortality.

Conclusions: PhenoAge-accel is positively associated with psoriasis risk. Furthermore, the coexistence of psoriasis and PhenoAge-accel are significantly associated with an increased risk of all-cause and CVD mortality.