Depression may increase stroke risk, impact stroke recovery

The research investigated 26,877 adults from the INTERSTROKE study. Participants came from 32 countries across Europe, Asia, North and South America, the Middle East, and Africa. They had a mean age of 62 years.

More than 13,000 participants had a stroke. The researchers matched them for age, sex, and racial or ethnic identity with another group of more than 13,000 participants who had not had a stroke. All completed questionnaires about cardiovascular risk factors, such as hypertension and diabetes.

The researchers collected information about depressive symptoms in the year leading up to the study. They asked participants whether they had felt sad or depressed for 2 or more consecutive weeks during those 12 months.

To assess whether participants might have chronic low mood, the researchers asked whether they had given up on making life improvements. They also recorded whether participants had ever taken antidepressants.

Those who had a stroke were more likely to have experienced depressive symptoms (18%) than those who did not have a stroke (14%). Those who reported having “given up on making life improvements” had a greater risk of stroke.

When the researchers adjusted for age, sex, education, physical activity, and other lifestyle factors, people with symptoms of depression had a 46% increased risk of stroke over those with no such symptoms.

The researchers found that the association between depressive symptoms and stroke was consistent across all country-income levels.

People with four or more depression symptoms were at higher risk of stroke than those with fewer symptoms.

Dr. Benesch commented on this finding, noting that “[t]his association between more severe depression and stroke risk is certainly worthy of more exploration and could be clinically significant.”

“An analogy would be that we know that smoking causes lung cancer. We also know that heavy smoking is more likely to cause lung cancer in someone who smokes every day versus someone who smokes once every 6 months. So there appears to be a dose-response relationship,” he added.

The study also found that although people with depressive symptoms did not have more severe strokes, they had worse outcomes 1 month after the stroke.

“These findings, at the bare minimum, should generate further investigation into this association between the two conditions. If that carries forward and we start to get some understanding of causality, then we can start talking about mitigating strategies.”

– Dr. Curtis Benesch

Several studies have previously linked depression with heart disease and stroke.

A 2011 meta-analysis of 17 studies showed that depression significantly increased the risk of a stroke, and that the increase was probably independent of other risk factors, such as hypertension or diabetes. However, this study could not determine whether there was a causal effect.

A larger meta-analysis published the same year, which looked at 28 prospective cohort studies, concluded that depression is prospectively associated with a significantly increased risk of developing stroke.

Another study, in 2020, found that people who experienced symptoms of depression were more likely to go on to develop heart disease or have a stroke.

Although the association was modest, it was present even in people whose symptoms were below the level of a depressive disorder.

This study did not identify the mechanisms by which depression might increase stroke risk, and previous studies have also been unable to do so.

Several studies have noted that depression commonly follows a stroke, but there is little research into whether depression might increase the likelihood of a stroke occurring.

One study has even suggested that there might be a reverse causality — that a previous undiagnosed stroke might have caused the depression.

Studies have also shown that depression can lead to people engaging in more adverse health behaviors, such as smoking and not complying with medical treatments. These behaviors may contribute to the risk of CVD and stroke.

Dr. Sandra Narayanan, board-certified vascular neurologist and neurointerventional surgeon at Pacific Stroke & Neurovascular Center at Pacific Neuroscience Institute in Santa Monica, CA, not involved in the current study, suggested another possibility.

“Depressive symptoms can be associated with increased stress, which can independently increase inflammation, [the] risk for future cardiovascular and cerebrovascular disease, and morbidity,” she said.

While the mechanisms that increase the risk may be unclear, this study shows that people with depression symptoms do have a higher likelihood of stroke and worse recovery from stroke. These findings suggest possible therapeutic pathways that may be effective.

People taking antidepressant medication did not have the same increased stroke risk as those with depression symptoms that were not treated with antidepressants.

The authors suggest that appropriate treatment might therefore lessen the risk of stroke. However, they caution that these medications may have other harmful effects.

For those with less severe depression symptoms, they suggest that psychological interventions might be an effective approach.

Dr. Narayan advised that the findings could inform treatments, noting that “[e]ducating patients undergoing treatment for depression, as well as screening those at risk for depression about their future stroke risk, is an important public health strategy, based on these study findings.”

“Including caregivers and PCPs [primary care physicians] in treatment plans and advising them of the additive risk of untreated depression is essential for longitudinal surveillance and treatment of cerebrovascular disease,” she added.