Comparative impact of mental and cardiovascular comorbidities on adverse outcomes in people with MS

Background: Comorbidities may exacerbate disease burden in people with Multiple Sclerosis (pwMS), yet their influence on disease progression and patient-reported outcomes (PROs) remains poorly understood. Understanding how comorbidities relate to progression and PROs can inform personalised care. Objectives: Identify comorbidity profiles in pwMS and assess their impact on MS type progression and PROs. Methods: This observational study analysed UK MS Register data from 2011-2025. Hierarchical clustering was based on cardiovascular and mental health comorbidities. Logistic and linear regression examined associations between clusters, comorbidities, progression and PROs. Results: Cluster analysis in 5,944 pwMS identified 3 clusters: 1 (no comorbidities, n=4,278), 2 (100% cardiovascular, 5% mental health, n=910), and 3 (98% mental health, 24% cardiovascular, n=756). Among participants with relapsing-remitting MS at baseline (n=4,942), compared to cluster 1, cluster 2 showed no difference in odds (OR 1.15, 95%CI: 0.93-1.43) whilst cluster 3 greater odds (OR 1.90, 95%CI: 1.53-2.35) of progressing to secondary-progressive MS, after adjusting for age, gender, and time since diagnosis. Depression showed the strongest association with progression. Comorbidities were associated with worse PROs, with anxiety and depression linked to lower psychological and physical symptoms. Conclusions: Mental health conditions clustered with cardiovascular multimorbidity consistently associated with poorer MS progression and prognosis, emphasising the need for integrated mental health management in pwMS.