Associations and mechanisms between stressful life events and degenerative valvular heart disease

Backgrounds: Degenerative valvular heart disease (VHD) is a great contributor to global morbidity and mortality, yet research on its risk factors has predominantly focused on traditional cardiovascular determinants. The role of psychosocial stressors, specifically stressful life events (SLEs), remains poorly understood. Methods: Using prospective data from 467 809 UK Biobank participants, information on stressful life events was assessed. Primary outcomes included incident aortic stenosis, aortic regurgitation, and mitral regurgitation. Cox proportional hazards models evaluated associations, while mediation analysis quantified contributions of mediators. Subgroup analyses were conducted to explore heterogeneity. Results: Exposure to stressful life events significantly increased risks of aortic stenosis (HR = 1.10 [95% CI, 1.05–1.14]), aortic regurgitation (HR = 1.07 [95% CI, 1.00–1.14]), and mitral regurgitation (HR = 1.08 [95% CI, 1.04–1.12]). Financial difficulties and serious illness/injury demonstrated strongest associations. Biological aging predictors, particularly PhenoAge, mediated 46% of the SLEs–VHD relationship. Cystatin C, C-reactive protein, and lifestyle factors (waist circumference, smoking) contributed modestly. Subgroup analyses revealed heightened susceptibility in women and younger individuals. Conclusions: Psychological stress is an independent risk factor for degenerative VHD, primarily mediated by biological aging. These findings advocate integrating psychosocial stress assessment into cardiovascular risk stratification and highlight the potential of stress mitigation and anti-biological aging interventions in preventive strategies.