Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2025 Jan;32(1):e16586.
doi: 10.1111/ene.16586.

Vascular risk factors are associated with grey matter atrophy in secondary progressive multiple sclerosis

Nevin A John  1   2 , Yingtong Li  1 , Floriana De Angelis  3 , Jonathan Stutters  3 , Ferran Prados  3   4   5 , Anisha Doshi  3 , Alberto Calvi  6 , Thomas Williams  3 , Domenico Plantone  7 , Thanh Phan  1   2 , Claudia A M Gandini Wheeler-Kingshott  3   8   9 , Frederik Barkhof  3   4   10   11 , Jeremy Chataway  3   10 ; MS‐SMART Investigators
Affiliations
Clinical Trial

Vascular risk factors are associated with grey matter atrophy in secondary progressive multiple sclerosis

Nevin A John et al. Eur J Neurol. 2025 Jan.

Abstract

Background: Comorbidities including vascular risk factors can be associated with whole and regional brain atrophy in multiple sclerosis (MS). This has been examined in mixed MS cohorts in prospective or observational studies; however, the association between vascular comorbidities (VCM) in secondary progressive MS (SPMS) and brain atrophy has been less well studied. The aim was to investigate the cross-sectional and longitudinal association between VCM, comorbidity burden and brain atrophy in SPMS.

Methods: Post hoc analysis of 445 participants 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, hyperlipidaemia) but also asthma, hypothyroidism and osteoporosis were recorded. Regional and whole brain volume (WBV), and percentage brain volume change were calculated using SIENAX and SIENA, respectively. Multiple linear regression was used to investigate the cross-sectional and longitudinal relationships between VCM, overall comorbidity count and whole brain, grey matter (GM) and white matter (WM) atrophy.

Results: The cohort was predominantly female (67%), mean age 55 with median EDSS 6.0. In total, 13% and 9% had hypertension and hyperlipidaemia, respectively. In cross-sectional regression models, VCM was associated with decreased cortical GM volume [(hypertension β = -0.30, 95%CI -0.54 to -0.06, p = 0.01) (hyperlipidaemia β = -0.37, 95%CI -0.64 to -0.09, p = 0.008)]; but not WBV. Having ≥2 comorbidities was also associated with decreased cortical GM volume (β = -0.36, 95%CI -0.61 to -0.10, p = 0.007). No relationship was observed between VCM/comorbidity count and whole brain or GM atrophy rate over 96 weeks.

Conclusions: People with SPMS with VCM or increased overall comorbidity burden showed reduced whole brain and especially cortical grey matter volumes, but no significant impact on subsequent 2-year atrophy rate was detected.

Keywords: comorbidities; multiple sclerosis; secondary progressive.

PubMed Disclaimer

Conflict of interest statement

FDA, JS, FP, AC, AE, TW, DP, AD, CWK and TP have no competing interests to declare. NAJ is a local principal investigator on commercial MS studies funded by Novartis, Roche and Sanofi. He has received speakers honoraria from Merck and congress sponsorship covering registration and travel from Novartis. FB serves on the editorial boards of Brain, European Radiology, Journal of Neurology, Neurosurgery & Psychiatry, Neurology, Multiple Sclerosis and Neuroradiology, and serves as consultant for Bayer Shering Pharma, Sanofi‐Aventis, Biogen‐Idec, TEVA Pharmaceuticals, Genzyme, Merck‐Serono, Novartis, Roche, Synthon, Jansen Research and Lundbeck. CAGW‐K has received research grants (PI and co‐applicant) from Spinal Research, Craig H. Neilsen Foundation, EPSRC, Wings for Life, UK MS Society, Horizon2020, NIHR/MRC, MRC and is a shareholder of Queen Square Analytics. In the last 3 years, JC has received support from the Efficacy and Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership and the Health Technology Assessment (HTA) Programme (NIHR), the UK MS Society, the US National MS Society and the Rosetrees Trust. He is supported in part by the National Institute for Health Research, University College London Hospitals, Biomedical Research Centre, London, UK. He has been a local principal investigator for a trial in MS funded by the Canadian MS society. A local principal investigator for commercial trials funded by: Actelion, Biogen, Novartis and Roche; has received an investigator grant from Novartis; and has taken part in advisory boards/consultancy for Azadyne, Biogen, Celgene, Janssen, MedDay, Merck, NervGen, Novartis and Roche.

Figures

FIGURE 1
FIGURE 1
Differences in baseline whole brain volume and cortical grey matter volume in those with hypertension and hyperlipidaemia (n = 445).
FIGURE 2
FIGURE 2
Differences in cortical grey matter volume by comorbidity count (n = 445).
See this image and copyright information in PMC

References

    1. Marrie RA, Cohen J, Stuve O, et al. A systematic review of the incidence and prevalence of comorbidity in multiple sclerosis: overview. Mult Scler J. 2015;21(3):263‐281. doi:10.1177/1352458514564491 - DOI - PMC - PubMed
    1. Thormann A, Magyari M, Koch‐Henriksen N, Laursen B, Sørensen PS. Vascular comorbidities in multiple sclerosis: a nationwide study from Denmark. J Neurol. 2016;263(12):2484‐2493. doi:10.1007/s00415-016-8295-9 - DOI - PubMed
    1. Thormann A, Koch‐Henriksen N, Laursen B, Sørensen PS, Magyari M. Inverse comorbidity in multiple sclerosis: findings in a complete nationwide cohort. Mult Scler Relat Disord. 2016;10:181‐186. doi:10.1016/j.msard.2016.10.008 - DOI - PubMed
    1. Magyari M, Sorensen PS. Comorbidity in Multiple Sclerosis. Front Neurol. 2020;11:851. doi:10.3389/fneur.2020.00851 - DOI - PMC - PubMed
    1. Salter A, Kowalec K, Fitzgerald KC, Cutter G, Marrie RA. Comorbidity is associated with disease activity in MS: findings from the CombiRx trial. Neurology. 2020;95(5):e446‐e456. doi:10.1212/WNL.0000000000010024 - DOI - PMC - PubMed

Publication types

MeSH terms

Grants and funding

LinkOut - more resources