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Individuals with a history of depressive symptoms have a 46% higher risk for stroke than those with no depression history, new research suggests.

Data from the international INTERSTROKE study also showed that those with depressive symptoms before a stroke had worse outcomes, including a significantly higher mortality rate in the first month after a stroke.

These findings build on prior research on the link between depression and stroke, including one study that showed an increased risk for incident stroke among those with a high number of depressive symptoms and another that found that worsening depression can precede stroke in older adults.

Dr Robert Murphy

“Depression is an important risk factor for acute stroke and is potentially a modifiable contributor to the global burden of stroke,” lead investigator, Robert Murphy, narcolepsy provigil side effects MB, a consultant in stroke and geriatric medicine and a researcher with the clinical research facility at the University of Galway, Ireland, told Medscape Medical News. “Even mild depressive symptoms were found in this study to be associated with increased risk of stroke and this adds to the literature that across the full range of depressive symptoms there is an association with increased risk of stroke.”

The findings were published online March 8 in Neurology.

Significant Stroke Risk

For the analysis, investigators collected data on 26,877 cases and controls across 32 countries who participated in INTERSTROKE, an international case-control study of risk factors for a first acute stroke. Participants were recruited between 2007 and 2015 and completed a series of questionnaires about stroke risk factors, including measures of depressive symptoms experienced in the past 12 months.

After adjusting for occupation, education, wealth index, diet, physical activity, alcohol consumption, and smoking history, having prestroke depressive symptoms was associated with greater odds for acute stroke (adjusted odds ratio [aOR], 1.46; 95% confidence interval [CI], 1.34 – 1.58), including both intracerebral hemorrhage (aOR, 1.56; 95% CI, 1.28 – 1.91) and ischemic stroke (aOR, 1.44; 95% CI, 1.31 – 1.58).

Stroke risk increased with increasing severity of depression, but even those with mild depression had a 35% increased risk (aOR, 1.35; 95% CI, 1.19 – 1.53).

The increased risk held even after adjusting further for diabetes, hypertension, atrial fibrillation, and body mass index, and work, home, and financial stress.

The association was consistent across geographical regions and age groups, but was stronger in men and in those without hypertension.

“This study looks at different constructs of depression and identifies that across the spectrum of mild, moderate and severe depressive symptoms that there is an association present with acute stroke and that a biological gradient emerges with increasing burden of depressive symptoms associated with increasing risk,” Murphy said.

An Antidepressant Mediating Effect?

While prestroke depressive symptoms were not associated with a greater odds of worse stroke severity, they were associated with worse outcomes (P < .001) and higher mortality (10% vs 8.1%; P = .003) 1 month after a stroke.

In a subgroup analysis, researchers found no association between depressive symptoms and stroke risk in patients who were taking antidepressants.

While no assumptions of causality can be drawn from these findings, “this subgroup analysis does suggest that an increased risk of stroke in those with depression may be attenuated if a patient is on appropriate treatment,” Murphy said. “This is an area that warrants further exploration.”

The mechanisms that link depression to stroke are unclear, but these findings offer strong evidence that this link exists, Murphy said.

“We adjusted for potential confounders in sequential models and after adjusting for traditional cardiovascular risk factors there was a consistent association between depressive symptoms and stroke identifying that there is likely an independent association between depression and stroke,” Murphy said.

Questions Remain

Commenting on the study for Medscape Medical News, Daniel T. Lackland DrPH, professor, Division of Translational Neurosciences and Population Studies, Department of Neurology, Medical University of South Carolina, Charleston, said it adds to a growing body of work on the association of stroke and depression.

“In this case, depression may be a risk factor for having a stroke,” said Lackland, who was not part of the study. In addition, the study suggests that “treating depression can have additional benefits beyond mental health, in this case, reduced stroke risks.”

However, it’s important, as with any observational study, that there may be confounding factors that may offer an alternative explanation for the findings.

“Further, it is often difficult to accurately assess depression in all individuals, and specifically in individuals who have had a stroke,” Lackland said. “While this particular study adds depression as a risk factor and suggests treatment of depression in reducing risks, it is important to emphasize that the traditional stroke risk factors including hypertension should [be] continually recognized and treat[ed] with high rigor.”

Neurology. Published online March 8, 2022. Abstract

The INTERSTROKE study was funded by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, the Canadian Stroke Network, the Swedish Research Council, the Swedish Heart Lung Foundation, AFA insurance, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), Merck Sharp & Dohme, the Swedish Heart Lung Foundation, Chest Heart & Stroke Scotland, and the Stroke Association (United Kingdom). Murphy and Lackland have reported no relevant financial relationships.

Kelli Whitlock Burton is a reporter for Medscape Medical News, covering neurology and psychiatry.

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