Meta-Analysis: Vascular Function Worse in People With MS

People with multiple sclerosis (MS) have notably worse vascular function, including greater arterial stiffness, compared with healthy controls, a new systematic review and meta-analysis has found. The findings suggest more research is needed to better understand how to manage vascular symptoms in patients with MS.¹

The study was published in Multiple Sclerosis and Related Disorders, and corresponding author Peixuan Zheng, PhD, of the University of Illinois Chicago, and colleagues, noted that vascular dysfunction can have significant negative impacts on various parts of the body. “As arteries stiffen, their ability to buffer pulsatility diminishes, and thus imposes increased mechanical stress that can result in damage to target organs such as heart, brain, and kidney,” they wrote.

In the general population, vascular function has been linked with the risk of comorbidities including cardiovascular and cerebrovascular disease, they noted. Better understanding the vascular sequelae of MS may similarly unlock predictive insights for people with MS, the investigators said. Yet, they said the existing evidence so far has not yielded clear answers. A scoping review published by the same research team last year found evidence of diminished vascular function in MS, though that review was not systematic.²

Zheng and colleagues sought to build on that report by completing a quantitative synthesis of existing data related to MS and vascular function. They undertook a systematic review that eventually yielded 14 studies that met inclusion criteria.¹ Together, those studies included 614 people with MS, of whom 72% were female. The participants ranged in age from 29.9 to 54.4 years old.

A meta-analysis of those studies showed a medium effect of MS on vascular health. They used Hedge’s g to calculate effect sizes as standardized mean differences (SMD), where positive outcomes represent worsening vascular function. That calculation showed people with MS had an SMD of 0.56 (95% CI, 0.08, 1.03; P = .02).

A significant difference in arterial stiffness was found (SMD 0.78; 95% CI, 0.21, 1.36; P = .008), but there were no significant differences in arterial structure or function outcomes, the investigators noted. “These findings may suggest pathophysiological changes in MS may particularly impact arterial stiffness more than other aspects of vascular health,” they wrote.

Zheng and colleagues used modeling to see whether certain moderating factors might affect risk. However, none of the potential moderators they assessed—including age, sex, body mass index (BMI), MS type, MS duration, disability level, smoking status, and hypertension status—had a significant moderating effect.

“Despite considerable heterogeneity across studies, the observed differences in vascular outcomes between MS and control samples were not significantly moderated by demographic (e.g., age, sex, BMI, and smoking), clinical (e.g., MS type, duration, and use of DMT [disease-modifying therapy]), or study (year or region) characteristics,” Zheng and colleagues wrote. The same was true when they assessed combinations of these variables.

The investigators noted that hypertension is one of the most common vascular comorbidities in MS, yet they said the studies in their analysis did not indicate a difference between the mean resting brachial blood pressure of the MS groups and the control groups. In addition, the mean brachial blood pressure of the MS groups did not meet the clinical definition of hypertension.

One possibility is that arterial stiffness precedes hypertension in MS and thereby contributes to disease progression and the development of comorbidities, they explained. They said clinicians might want to do a more comprehensive assessment of vascular function in patients with MS, assessing not only their patients’ blood pressure, but also factors like arterial stiffness and endothelial function.

Zheng and colleagues said questions around the development of vascular comorbidities deserve more study.

“Such research will inform future development of targeted, evidence-based interventions for improving vascular health and managing comorbid conditions among the MS population,” they concluded.

References

1. Zheng P, DuBose NG, DeJonge SR, Jeng B, Hibner BA, Motl RW. Vascular function in multiple sclerosis: Systematic review with meta-analysis. Mult Scler Relat Disord. 2024;91:105902. doi:10.1016/j.msard.2024.105902
2. DuBose NG, DeJonge SR, Jeng B, Motl RW. Vascular dysfunction in multiple sclerosis: Scoping review of current evidence for informing future research directions. Mult Scler Relat Disord. 2023;78:104936. doi:10.1016/j.msard.2023.104936