People with multiple sclerosis (MS) and depression had a higher risk of incident vascular disease and mortality compared with matched controls, a retrospective study found.
The 10-year hazard of all-cause mortality was 1.75-fold greater in controls with depression (95% CI 1.59- 1.91), 3.88-fold greater in MS patients without depression (95% CI 3.66-4.10), and 5.43-fold greater in MS patients with depression (95% CI 4.88-5.96) than it was in controls without depression, reported Raffaele Palladino, MD, PhD, of the Imperial College of London in the United Kingdom and co-authors.
The interaction between MS status and depression was synergistic for all-cause mortality, with 14% of the observed effect attributable to the interaction, they wrote in Neurology.
“We do not know why the combination of depression and MS has a synergistic effect on mortality, but several factors might play a role, including inflammation and immune dysregulation, as well as dysregulation of the hypothalamic pituitary axis,” Palladino said in an email to BreakingMED.
“Furthermore, depression might be associated with poorer cardiovascular risk factor management and health behaviors (diet, physical activity) which can negatively affect MS as well as other aspects of health,” he continued. “Additional studies should be conducted to evaluate whether effectively treating depression in people with MS reduces vascular risk and therefore reduces disability progression and mortality.”
The study included adults with MS and matched controls from the Clinical Research Datalink database in England between January 1987 and September 2018. The researchers used regression models to test associations between MS with and without depression, time to incident vascular disease, and mortality with respect to controls. Synergistic interactions were identified when the combined effect of two variables exceeded their expected additive effect (departures from additivity).
People in both the MS group (n=12,251) and the control group (n=72,572) had a mean age of about 45. Both groups were made up predominantly of women. Baseline depression was present in 21% of people with MS and 9% of controls.
MS patients with or without depression had an increased risk of incident vascular disease compared with matched controls without depression. For MS patients without depression, the HR of incident vascular disease was 1.48 (95% CI 1.23-1.74); for MS patients with depression, the HR was 3.30 (95% CI 2.37-4.23).
“Controls with depression also had an elevated risk of incident vascular disease, similar to that of persons with MS and depression,” the researchers noted. The interaction between MS status and depression with incident vascular disease was not synergistic.
Depression also was associated with a two-fold increased risk of cardiovascular disease mortality in people with and without MS, compared with controls who did not have depression.
“In this study, the authors observed departures from additivity in those with MS and depression compared to controls without depression for all-cause mortality, but not incident vascular disease and cardiovascular mortality,” wrote Amber Salter, PhD, of UT Southwestern Medical Center in Dallas, in an accompanying editorial. “The attributable proportion showed a 14% increased hazard of mortality in those with both MS and depression compared to controls without depression.”
“The cohort had over 12,000 persons with MS and six controls matched to each person with MS which permitted robust representation in each of the four groups, controls with and without depression and MS persons with and without depression,” she added.
Depression is the most frequent comorbidity in people with MS, affecting up to 30%, and has been linked to a significant increased risk in disability progression. In general populations, the lifetime prevalence of depression has ranged from 2% to 21% according a 2020 systematic review, and has been associated with increased relative risks of cardiovascular disease and all-cause mortality.
“Much less is known about these associations in the MS population,” Palladino and co-authors observed.
A 2018 study of immune-mediated inflammatory diseases found a synergistic relationship between MS and depression on mortality, including suicide risk. A 2020 autopsy study of MS and vascular disease reported that “data argue against a common primary trigger for atherosclerosis and multiple sclerosis but suggest that an excess burden of cerebral small vessel disease in multiple sclerosis may explain the link between vascular comorbidity and accelerated irreversible disability.”
Findings from the current study “build on our previous work which showed an overall 30% increased hazard of any macrovascular disease compared to a matched control population and underscore the importance of identifying depression in the MS population,” Palladino and co-authors noted.
Limitations included lack of body mass index and physical activity data in the analysis. The researchers also were unable to evaluate the proportion of deaths due to suicide to see what effect this may have had on mortality associated with depression in MS.
People with multiple sclerosis (MS) and depression had a high risk of incident vascular disease and mortality compared with matched controls, a retrospective study found.
The 10-year hazard of all-cause mortality was 5.43-fold greater in MS patients with depression than it was in controls without depression. The interaction between MS status and depression was synergistic for all-cause mortality.
Paul Smyth, MD, Contributing Writer, BreakingMED™
The authors report no targeted funding.
Palladino has nothing to disclose.
Salter reports no disclosures relevant to the manuscript.
Cat ID: 36
Topic ID: 82,36,730,36,192,55,921,925