Association of cardiovascular-kidney-metabolic health and social connection with the risk of depression and anxiety.

Background: To explore the association of cardiovascular-kidney-metabolic (CKM) health with the risk of depression and anxiety and to investigate the joint association of CKM health and social connection with depression and anxiety.

Methods: This prospective cohort study included 344 956 participants from the UK Biobank. CKM syndrome was identified as a medical condition with the presence of metabolic risk factors, cardiovascular disease, and chronic kidney disease, and was classified into five stages (stage 0-4) in this study. Loneliness and social isolation status were determined by self-reported questionnaires. Cox proportional hazards models were applied for analyses.

Results: Compared with participants in stage 0, the HRs for depression were 1.17 (95% CI 1.10-1.25), 1.40 (95% CI 1.33-1.48), and 2.14 (95% CI 1.98-2.31) for participants in stage 1, 2-3, and 4, respectively. Similarly, participants in stage 2-3 (HR = 1.20, 95% CI 1.14-1.26) and stage 4 (HR = 1.63, 95% CI 1.51-1.75) had greater risks of incident anxiety. We found additive interactions between loneliness and CKM health on the risk of depression and anxiety. Participants simultaneously reported being lonely and in stage 4 had the greatest risk of depression (HR = 4.44, 95% CI 3.89-5.07) and anxiety (HR = 2.58, 95% CI 2.21-3.01) compared with those without loneliness and in stage 0. We also observed an additive interaction between social isolation and CKM health on the risk of depression.

Conclusions: Our findings suggest the importance of comprehensive interventions to improve CKM health and social connection to reduce the disease burden of depression and anxiety.