Vascular function in multiple sclerosis: Systematic review with meta-analysis

Abstract

Background

Vascular comorbidities are prevalent in persons with multiple sclerosis (MS), yet less is known about underlying vascular function (VF). We performed a systematic review with meta-analysis of studies that compared VF in persons with MS and healthy controls and examined factors that may moderate the difference in vascular outcomes between groups.

Methods

We conducted a systematic search using PubMed/MEDLINE, CINAHL, and Embase from inception through March 2024. The search identified studies that included comparisons of VF between MS and controls on a range of function and structure outcomes (e.g., pulse wave velocity, augmentation index, arterial diameter, intima-media thickness, flow-mediated dilation). Effect sizes were calculated as standardized mean differences (SMD) using Hedge's g with a positive effect indicating worse VF in MS than controls. The meta-analysis involved a multilevel random effects model with follow-up moderator analyses.

Results

Fourteen studies met the inclusion criteria and yielded 49 effect sizes for meta-analysis. The MS subjects (N = 614) were predominantly female (72.0 %), with mean ages ranging from 29.9 to 54.4 years. There was a moderate difference in VF between persons with MS and healthy controls (SMD [95 % CI] = 0.56 [0.08, 1.03]; p = 0.02), and the effects were heterogenous (Q₄₈=634.5, p < 0.01; I²=94.39 %). There was a greater difference in arterial stiffness between MS and controls (0.78 [0.21, 1.36], p = 0.008), but not in other arterial structure or function outcomes (p > 0.05). No significant moderators were detected (p > 0.05).

Conclusions

The cumulative evidence supports that persons with MS have worse VF, notably greater arterial stiffness, than healthy controls. Such findings support future research on the cause, consequences, and management of arterial stiffness among persons with MS.