Depression Greatly Raises Patients’ Risk of Vascular Disease, Death

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by Steve Bryson, PhD |

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Depression in multiple sclerosis (MS) patients greatly raises their risk of vascular disease and death by any cause, a study that compared this patient group with other patients and a matched public reported.

Its researchers recommended further work to determine “whether effectively treating depression” might lower these risks for these people.

The study, “Interface of Multiple Sclerosis, Depression, Vascular Disease, and Mortality: A population-Based Matched Cohort Study,” was published in the journal Neurology.

Significantly higher rates of depression are reported in people with MS compared with the general population, which  can worsen disease disability and limit quality of life.

In the general population, depression is also associated with a 30% greater risk of vascular (blood vessel) disease — the cause of heart attacks and strokes — and a 70% increased risk of mortality by any cause. These risks rise further in those with more severe depression.

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However, little is known about vascular disease and mortality risks in MS patients with depression.

“We aimed to assess whether the association between depression, vascular disease, and mortality differs in people with MS as compared with age, sex, and general practice-matched controls,” the researchers, based at the Imperial College of London in the U.K. and the University of Manitoba in Canada, wrote.

Using the Clinical Research Datalink database for England, they identified 12,251 adults diagnosed with MS from 1987 to 2018. For each MS case, six matched people without MS were randomly selected as controls — 72,572 people in total.

In their analyses, the researchers accounted for age, sex, ethnicity, smoking status, type 2 diabetes, and vascular disease or diabetes medications. Body weight and physical activity were not included in this study. (Diabetes is a risk factor for cardiovascular and cerebrovascular disease, the researchers noted, and more so in women than in men.)

Depression was diagnosed in 21% of these patients within a year of their MS diagnosis or first MS-related event, and diagnosed in 9% of matched controls. Overall, depression was more likely to be found in women and younger individuals, and more than 40% of patients and controls with depression were smokers.

Notably, MS patients without depression at diagnosis or first event were seen to be at a higher risk of vascular disease than MS patients with depression at that same time point.

Over 10 years, the incidence per 100,000 person-years — a measure that takes into account the number of people in the study and the amount of time each person was followed — of any vascular disease for controls with depression was twice as high as those without depression (1.34 vs. 0.66).

Among MS patients, vascular disease incidence was also double among those with depression relative to patients without it (2.44 vs. 1.17). The incidence rate was similar for vascular disease that affected the heart, brain, or other large blood vessels.

This vascular risk was also higher for MS patients — with or without depression — than for matched controls.

“We observed that MS is associated with increased risks of vascular disease which are not fully accounted for by traditional vascular risk factors such as diabetes, hypertension [high blood pressure] and smoking,” the team wrote.

MS patients and controls with depression had a 3.3 times greater risk of a vascular disease-related event, such as heart attack or stroke, than did a matched public without depression. Among patients without depression, the risk was 1.48-fold higher.

An examination of sex differences found that women with MS and depression had the greatest risk for vascular disease. In comparison, men with MS and depression were not at a significantly greater risk of vascular disease, although “the direction of the effect was similar to what was observed in the population overall,” the researchers wrote.

Depression was also linked with an increased risk of mortality due to any cause (all-cause), and mortality due to cardiovascular disease. The all-cause mortality incidence (per 100,000 person-years) was slightly higher in controls with depression than those without (3.59 vs. 2.53), but similar among MS patients with and without depression (10.30 vs. 10.58).

Even so, compared with controls without depression, the mortality risk at 10 years was 5.4-times higher patients with depression, 3.9 times greater in MS patients without depression, and 1.8-fold higher among controls with depression.

In total, MS status and depression could explain about for 14% of mortality, rising to 21% when limiting the analysis to men. This suggested an additive, or synergistic effect, in which MS and depression together were associated with a higher risk of all-cause mortality compared to MS and depression assessed separately.

“The interaction between MS status and depression was synergistic, with 14% of the observed effect on mortality attributable to the interaction,” the researchers wrote.

Finally, the risk of cardiovascular disease-related mortality was twice as high in MS patients and controls with depression, than in controls without depression.

“Depression is associated with increased risks of incident vascular disease and mortality in people with MS and the effects of depression and MS on all-cause mortality are synergistic,” the investigators wrote.

“We can only speculate as to why synergistic effects of depression and MS were observed on all-cause mortality,” they added. “Possibly this could reflect adverse effects of depression on adherence to disease-modifying therapy, or on depression-associated health behaviours such as smoking.”

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