Depression May Raise the Risk of Vascular Disease and Mortality in Patients with Multiple Sclerosis

July 2022

Previous studies have found that >20% of patients with multiple sclerosis (MS) also have depression. Depression increases the risk of vascular disease and all-cause mortality in the general population, but these associations have not been well-studied in patients with MS.

The investigators selected a total of 12,251 patients with MS and 72,572 age- and sex-matched controls without MS from the Clinical Research Datalink database in England. The study period covered 1987 to 2018. They searched the records for codes for depression and then looked for diagnoses of vascular diseases that occurred after the diagnosis of MS or after the equivalent date for matched controls over the following 10 years. The vascular disease outcomes included acute coronary syndrome, cerebrovascular disease, and composite macrovascular disease (acute coronary syndrome, cerebrovascular disease, and peripheral arterial disease). Other outcomes were all-cause mortality and cardiovascular mortality.

As expected, the investigators found higher rates of depression in patients with MS than matched controls, 21% versus 9%, respectively. They also found a higher rate of incident vascular disease in patients with MS compared with matched controls.

Comorbid depression was associated with an increased relative risk of incident vascular disease in matched controls. The same association was also found in patients with MS. The effects of MS and depression on the relative risk of incident vascular disease were additive.

The investigators also compared the 10-year all-cause mortality risk of each group relative to that of matched controls without depression. They found that MS and depression greatly raised the risk of all-cause mortality. Depression in controls was associated with a 1.8-fold increased risk, MS without depression was associated with a 3.9-fold increased risk, and MS with depression was associated with a 5.4-fold increased risk compared with controls without depression. The investigators calculated that 14% of the effect on all-cause mortality could be attributed to a synergistic interaction of MS with depression; however, the association between MS and depression on cardiovascular mortality was additive.

In general, the investigators found that the differences between MS groups and matched controls were stronger in women than men.

Although this study suggests that depression raises the risk of vascular disease in patients with or without MS, the reverse may also occur. The investigators noted that previous studies have shown that various comorbidities, such as ischemic disease and inflammatory disorders, are associated with incident depression in patients with MS. They speculated that “coupled with our findings, these prior studies suggest that bidirectional relationships exist between depression and vascular disease in MS.”

It is not known how depression would raise the risk of incident vascular disease or mortality or how depression and MS could act synergistically to raise the risk of all-cause mortality. The investigators mentioned possible explanations, such as effects on inflammation, the immune system, and the hypothalamic-pituitary axis.

The results of this study suggest that therapy for depression in patients with MS may have benefits to physical as well as mental health. The authors concluded that “additional studies should be conducted to evaluate whether effectively treating depression in the MS population (perhaps with a lower threshold than those not affected by MS) reduces the risk of incident vascular disease and therefore reduces disability progression and mortality.”

Source

Palladino R, Chataway J, Majeed A, Marrie RA. Interface of multiple sclerosis, depression, vascular disease, and mortality: a population-based matched cohort study. Neurology. 2021;97:e1322-e1333.

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