Vascular Comorbidities and an Increased Comorbidity Score Are Associated With Disability and Disability Progression in Secondary Progressive Multiple Sclerosis

Background: Vascular risk factors are associated with increased disease activity and disability progression in multiple sclerosis (MS). This has been studied mainly in cohorts with relapsing–remitting MS. However, the association between vascular comorbidities (VCM) and clinical disability in secondary progressive MS (SPMS) is less well studied. Our aim was to investigate the association between VCM, non-VCM, comorbidity burden and both physical and cognitive performance in SPMS. Methods: Longitudinal analysis of 445 patients from the MS secondary progressive multi-arm trial (MS-SMART)–a multi-arm multicentre phase-2b randomised placebo-controlled trial of three agents in SPMS (NCT01910259). VCM (hypertension and hyperlipidaemia) and non-VCM (asthma, hypothyroidism and osteoporosis) were recorded. A comorbidity score was also determined (0, 1, ≥ 2). Physical disability and processing speed were assessed at baseline, 48- and 96 weeks. Multiple linear regression and mixed models were used to investigate the cross-sectional and longitudinal relationships between baseline VCM, non-VCM, comorbidity score and clinical outcome measures. Results: The cohort was predominantly female (67%), median Expanded Disability Status Scale (EDSS) 6.0. 13% and 9% had hypertension and hyperlipidaemia (VCM), respectively. 7%, 9% and 5% had asthma, hypothyroidism and osteoporosis (non-VCM), respectively. Co-morbidity counts were 0,63%; 1, 23% and with > = 2, 11%. In cross-sectional models, both hypertension (β = 0.36, 95% CI 0.18–0.54) and an increased comorbidity count (β = 0.47, 95% CI 0.28–0.67) were associated with higher EDSS scores. In longitudinal models, hyperlipidaemia (β = 0.22, 95% CI 0.02–0.42) and increased comorbidity count (β = 0.21, 95% CI 0.01–0.41) were associated with increased EDSS scores over 48/96 weeks. No associations were seen with the non-VCM. Conclusion: VCM and also increased comorbidity burden per se are associated with increased disability. Disability worsening over 96 weeks was most evident in those with hyperlipidaemia and increased comorbidity burden.