Abstract
Introduction: Vascular comorbidities (VCM) are common in patients with multiple sclerosis (MS). VCM are associated with increased disease activity and disability progression, but long-term clinical follow-up data in larger cohorts is limited.
Objectives/Aims: To investigate whether VCM are associated with relapse rates or disability progression in relapsing-remitting MS (RRMS).
Methods: We analysed longitudinal data from MSBase, an international prospective registry of patients with MS. Adults with RRMS, no relapses over the preceding year and no commencement or switching of disease-modifying therapy (DMT) were identified from 2015–2017. Included participants were followed up for 5 years. Baseline VCM (hypertension, hyperlipidaemia, diabetes, ischaemic heart disease) were analysed as individual VCM and as cumulative count of VCM (0/1/2+). Poisson and Cox regression were used to investigate the association between VCM, relapse rates and disability progression over 5 years of follow-up, respectively, with models adjusted for age, sex, disease duration and baseline DMT. As a sensitivity analysis, we analysed a subgroup of 18 sites participating in the MSBase Safety substudy with more complete registry data.
Results: 42185 participants were followed-up over 5 years. The mean age was 44.4 years (SD 12.7), and 72.3% were female. Recorded VCM were hypertension (n=912), diabetes (n=451), hyperlipidaemia (n=325) and ischaemic heart disease (n=186). Median Expanded Disability Status Scale (EDSS) was 2.0 at baseline (IQR 1.0–4.0) and 2.5 at 5 years (IQR 1.5–5.5).
7454 participants (17.7%) had 1 or more relapses over 5 years. Hypertension was associated with increased relapse rate (IRR [95% CI] 1.75 [1.55–1.99]; p<0.001), as were hyperlipidaemia (IRR 1.93 [1.58–2.35]; p<0.001) and diabetes (IRR 1.89 [1.61–2.22]; p<0.001), but not ischaemic heart disease (IRR 1.28 [0.96–1.70]; p=0.09). The relapse rate was increased in those with 1 VCM (IRR 1.81 [1.64–2.00]; p<0.001) and 2 VCM+ (IRR 1.74 [1.36–2.23]; p<0.001), compared to those with no VCM. In the sensitivity analysis, hypertension (IRR 1.20 [1.01–1.42]; p=0.04), diabetes (IRR 1.74 [1.44–2.09]; p<0.001) and 1 VCM (IRR 1.37 [1.20–1.57]; p<0.001) were also associated with increased relapse rates. VCM were not associated with EDSS worsening.
Conclusion: Vascular risk factors are associated with increased disease activity over 5 years in RRMS.