NOMAS: Depression Tied to Increased Stroke Risk

Batya Swift Yasgur, MA, LSW

March 20, 2019

Having a high number of depressive symptoms may be associated with an increased risk for stroke, new research suggests.

Investigators used data from the Northern Manhattan Study (NOMAS) MRI-Sub-Study, an ongoing cohort study of primarily Hispanic older adults who were clinically free of stroke at baseline and followed for a median of 14 years.

Results showed that participants with elevated depressive symptoms were at significantly increased risk for incident ischemic stroke compared with those who showed no signs of depression.

"The take-home message is that we found an association between elevated depressive symptoms and incident ischemic stroke," lead author Marialaura Simonetto, MD, a postdoctoral associate in the Department of Neurology at the University of Miami's Miller School of Medicine in Florida, told Medscape Medical News.

However, "this is an observational study that may not suggest causality or changes in clinical practice," warned Simonetto.

The findings will be presented at the American Academy of Neurology (AAN) 2019 Annual Meeting in May.

Mood, Stroke Risk "Underexplored"

"Depression has been associated with cardiac morbidity and mortality," Simonetto said. "However, the impact of mood and depressive symptoms on risk of incident stroke has been underexplored."

The current analysis is part of the NOMAS study, a long-standing collaboration between Columbia University and the University of Miami funded by the National Institute of Neurological Disorders and Stroke. NOMAS "aims to investigate stroke, stroke risk factors, and stroke epidemiology in minority populations," Simonetto reported.

"In this study, we aimed to analyze how mood and depressive symptoms may affect stroke risk," she added.

The hypothesis was that depressive symptoms would be associated with elevated risk for ischemic stroke.

To investigate that question, the researchers assessed 1104 participants (mean age, 70 ± 9 years, 61% women, 69% Hispanic) who were free of stroke at MRI baseline.

They assessed depressive symptoms using the Center for Epidemiologic Studies–Depression Scale (CES-D). An "elevated" symptom score was 16 or higher.

Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for incident ischemic stroke after adjusting for age, sex, race/ethnicity, years of education, smoking status, moderate-to-heavy physical activity, alcohol consumption, diabetes, and hypertension.

The participants were followed for up to 14 years (median, 11 years).

Complex Mechanisms

Elevated depressive symptoms were found in 198 participants (18%) at MRI baseline.

During the follow-up period, 101 participants had incident strokes, of which 87 were ischemic strokes.

When the researchers used Kaplan–Meier estimates, they found that the cumulative incidence of stroke of any type and of ischemic stroke were 14% (95% CI, 10% – 20%) and 13% (95% CI, 9% – 18%), respectively.

In adjusted models, participants with elevated depressive symptoms were at significant increased risk for ischemic stroke (HR, 1.75; 95% CI, 1.06 – 2.88). Every 5-point increase in CES-D score conferred a 12% greater risk for ischemic stroke (HR, 1.12; 95% CI, 1.01 – 1.25).

"Our study did not investigate the mechanisms that may explain the association between elevated depressive symptoms and risk of incident ischemic stroke," Simonetto noted.

"The mechanisms behind this association are complex," she added. "Depression might be a risk factor for ischemic stroke through complex brain mechanisms that are not yet fully understood, or it might be that people with depression may encounter obstacles accessing healthcare."

Missing Factors?

Commenting on the study for Medscape Medical News, Donn Dexter, MD, assistant professor of neurology at Mayo Clinic College of Medicine and Science and chair of education at Mayo Clinic Health System in Eau Claire, Wisconsin, said that NOMAS "follows a really solid racially and ethnically diverse Manhattan population."

In addition, the findings "underscore the importance of addressing and treating depression," said Dexter, who was not involved with the current research.

The investigators did "a nice job" of matching for age, sex, race, ethnicity, lifestyle factors, and comorbidities, but "one concern I have is that they might be missing other factors that could be playing a role," he added. 

Examples might be whether patients were taking medications for their comorbidities or whether they had obstructive sleep apnea, "which can often look like depression; and we know that obstructive sleep apnea is a risk factor for stroke," he said.

However, "I am hoping that when we get all the data to look at, that [the researchers] have taken a more careful look at that," said Dexter.

Several Take-Home Messages

Also commenting for Medscape Medical News, Harold P. Adams Jr, MD, professor of neurology at the University of Iowa's Carver College of Medicine in Iowa City, noted that a "particular attribute of this study is the large number of minority patients, in particular Hispanic patients, in the population."

The study "demonstrates that depression is a potential risk factor for stroke," said Adams, who was not involved with the research. "While the contribution of depression may be indirect rather than direct, such as with diabetes or hypertension, it does suggest that depression is a factor that needs to be addressed by healthcare providers."

Moreover, "the finding that the more severe the depression, the higher the risk of stroke, is also a contribution," he added.

The study has several important take-home messages, including highlighting that depression is "an important medical illness that has a potential for a number of complications, including stroke," and that the association between depression and stroke is strongest in older women, Adams said.

Simonetto added that the mechanisms for this association "are complex and not yet fully elucidated, and further studies to better understand how mood and depressive symptoms may affect and increase stroke risk are warranted in order to design appropriate primary prevention strategies."

The NOMAS study is supported by the National Institute of Neurological Disorders and Stroke (NINDS). No authors' disclosures are listed. Dexter and Adams have disclosed no relevant financial relationships.

To be presented at the American Academy of Neurology (AAN) 2019 Annual Meeting, May 4-10.

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