Cardiovascular Risk Factors Linked to Brain Atrophy in MS

Dr Raffaello Bonacchi

The presence of cardiovascular risk factors in patients with multiple sclerosis (MS) is associated with a greater degree of brain atrophy even in young patients who are unlikely to have small vessel disease, a new study has shown.

The results were presented by Raffaello Bonacchi, MD, Vita-Salute San Raffaele University, Milan, Italy, on September 11 at the 8th Joint European Committee for Treatment and Research in Multiple Sclerosis-Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.

“Our results suggest that even low levels of exposure to cardiovascular risk factors are important in MS and might affect brain atrophy — and therefore long-term disability — even in young patients,” Bonacchi told Medscape Medical News

“It is not only smoking,” he added. “Other cardiovascular risk factors also appear to be implicated. We found a synergistic effect of the different risk factors.”

These are only preliminary data and need to be confirmed in other studies,” he said, “but it does suggest that MS neurologists need to pay attention to comprehensive care — not just MS disease activity.

“They also need to be discussing lifestyle with their patients, evaluating their cardiovascular risk factors, and giving advice on stopping smoking, lowering blood pressure, cholesterol, etc.”

Brain Changes

Bonacchi explained that previous studies have suggested a relationship between cardiovascular risk factors and changes on magnetic resonance imaging (MRI) and clinical outcomes in patients with MS that may be mediated by small vessel disease and/or inflammation.  

“Small vessel disease is widespread in the population over 50 years of age, but in this study we wanted to look at the impact of cardiovascular risk factors in younger patients with MS who are not likely to have much small vessel disease to try and see whether there is still a relationship with brain atrophy or white/gray matter lesions,” he said.

Previous studies have not set an age limit for examining this relationship and they have also assessed the presence versus absence of cardiovascular risk factors, without attempting to grade the strength of exposure, he noted.

For the current study, the researchers examined several cardiovascular risk factors and in addition to just being present or absent. They also graded each risk factor as being stringent or not depending on a certain threshold.

For example, smoking was defined as a threshold of 5 pack-years (smoking 5 cigarettes a day for 20 years or 20 cigarettes a day for 5 years). And the more stringent definition was 10 pack-years.

For hypertension, the stringent definition was consistently high blood pressure levels and use of antihypertensive medication, with similar definitions used for cholesterol and diabetes.

This was a cross-sectional observational study in 124 patients with MS and 95 healthy controls. The researchers examined MRI scans and neurological exams and investigated whether the amount of cardiovascular risk factors a patient was exposed to was associated with degree of brain atrophy and white matter/gray matter volume. Results were adjusted for age, sex, disease duration, phenotype (relapsing-remitting versus progressive MS) and treatment.

Results showed no significant difference if patients were exposed to at least one classical risk factor versus no risk factors.

But if a patient had at least two classical risk factors, significant differences were found in gray matter, white matter, and total brain volume.

Patients with MS and no risk factors had a mean brain volume of 1524 mL versus 1481 mL in those with at least two risk factors, a difference that was significant (P = .003).

Mean gray matter volume was 856 mL in MS patients without cardiovascular risk factors and 836 mL in those with at least two risk factors (P = .01)

Mean white matter volume was 668 mL in MS patients without cardiovascular risk factors and 845 mL in those with at least two risk factors (P = .03).

“This is one of the first studies to have graded degrees of risk factors and we found one stringent risk factor was associated with the same effects on brain atrophy as two less stringent risk factors,” Bonacchi reported.

Healthy controls showed no differences in any of the brain volume outcomes in those with or without cardiovascular risk factors.

“As our population was under aged 50 years, who are unlikely to have much small vessel disease, our results suggest that the influence of cardiovascular risk factors on brain atrophy in MS is not just mediated through small vessel disease and is probably also mediated by increased inflammation,” Bonacchi suggested. 

Impact of CV Risk Factors

Commenting on the study for Medscape Medical News, Dalia Rotstein, MD, assistant professor, department of neurology, University of Toronto, Ontario, Canada, session cochair, said: “This is an interesting study that captures the impact of cardiovascular risk factors on various measures of brain atrophy in MS.”

The cohort was quite young, under age 50, and the effect on brain atrophy was increased with more severe cardiovascular risk factors, she noted.

“The investigators compared these effects to a population of healthy controls and did not observe as substantial an effect in controls. However, they were likely underpowered for the analysis in the healthy controls because of a relatively small number of subjects with cardiovascular risk factors in this group,” Rotstein noted.

“More research is needed to determine whether the observed relationship is unique to MS and whether treating cardiovascular risk factors may help protect against neurodegeneration in MS,” she added.

Also commenting, ECTRIMS president, Bernhard Hemmer, PhD, said, “This study provides some evidence that CV risk factors contribute to the brain atrophy that occurs in MS patients. This result is not too surprising because atrophy in MS is mainly driven by age and the extent of inflammatory disease activity. It is well known that CV risk factors are associated with microangiopathy, and this will lead to cerebral lesions and eventually to brain atrophy. Thus, it makes perfect sense that this factor also contributes to brain atrophy in MS.”

Hemmer,  who is director of the neurology clinic at the Technical University of Munich, Germany, added that one caveat would be that the study is rather small. 

But he concluded: “MS patients should be screened for vascular risk factors and treated if possible to avoid further MS-independent damage to the brain.”

Bonacchi has reported no relevant financial relationships. Rotstein has reported acting as a consultant for Roche, Alexion, Novartis, EMD Serono, and Sanofi Aventis.

ECTRIMS-ACTRIMS 2020. Presented September 11, 2020. Session PS04.05.

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