Association between neuroticism, genetic susceptibility, and peripheral artery disease risk: a prospective study in UK Biobank.

BACKGROUND

Neuroticism is one of five personality traits characterized by a tendency to generate and intensify negative emotions in the face of stress and is linked to an elevated incidence of cardiovascular disease (CVD). However, the pathogenesis of peripheral artery disease (PAD) differs from other CVDs. This study aimed to investigate the association of neuroticism with PAD and to examine whether genetic susceptibility influences this association.

METHODS

399,730 PAD-free individuals from the UK Biobank were included. Participants were categorized into high (≥ 4 scores) and low neuroticism (< 4 scores) groups based on the median score from a self-questionnaire assessing 12 neuroticism-related behaviors. Cox proportional hazard models were employed to evaluate the association between neuroticism and PAD, as well as the combined and stratified effects of neuroticism and genetic susceptibility on PAD.

RESULTS

After a median follow-up of 13.6 years, 4269 (1.1%) participants developed PAD (mean age, 56.4 years; 53.7% female). High neuroticism was associated with significantly increased risk of PAD (hazard ratios [HR] 1.119; 95% confidence interval [CI] 1.051–1.192) compared to low neuroticism. Genetic analyses indicated no significant interaction between genetic susceptibility and neuroticism in relation to PAD (P for interaction = 0.635). Participants with both high PRS and high neuroticism had an HR was 1.451 (95% CI 1.322–1.592) compared to those with low PRS and low neuroticism.

CONCLUSIONS

High neuroticism was associated with an increased risk of PAD, independent of genetic susceptibility. Active mental health monitoring may benefit high-risk populations.