Social Disconnection, Genetic Risk, and the Incidence of Degenerative Valvular Heart Disease: A Population‐Based Cohort Study

Background Degenerative valvular heart disease (VHD) is increasingly recognized as a major public health concern in aging populations. Although traditional cardiovascular risk factors have been extensively investigated, the role of loneliness and social isolation has remained largely overlooked in the context of valvular pathology. Methods We conducted a prospective cohort study involving 462 917 participants from the UK Biobank, free of VHDs at baseline. Loneliness and social isolation were assessed using validated questionnaires. Results During a median follow‐up of 13.9 years, 11 003 cases of degenerative VHD were documented. Among them, there were 4280 cases of aortic valve stenosis and 4693 cases of mitral valve regurgitation. In fully adjusted models using no loneliness as reference, the highest loneliness level was associated with significantly increased risks of degenerative VHD (hazard ratio [HR], 1.19 [95% CI, 1.09–1.28]), aortic valve stenosis (HR, 1.21 [95% CI, 1.06–1.37]) and mitral valve regurgitation (HR, 1.23 [95% CI, 1.09–1.39]) (all P for trend <0.001). This association was consistently observed for degenerative VHD‐related events. In contrast, no significant associations were observed for social isolation. Additionally, loneliness was associated with an increased risk of degenerative VHD, independently of genetic background, but the highest risk occurs in individuals with both high genetic risk and elevated loneliness ( P <0.001). In mediation analyses, unhealthy lifestyles were identified as significant mediators in the association between loneliness and incident degenerative VHD. Conclusions Loneliness, rather than social isolation, was significantly associated with an increased risk of degenerative VHD. Our findings highlight novel opportunities for nonpharmacological interventions aimed at managing degenerative VHD.