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Depression, Stress, Hostility All Linked to Increased Stroke
Medscape Medical News
July 10, 2014

Depression, chronic stress, or exhibiting hostility or cynicism can increase the risk for stroke, and in the case of having a cynical outlook on the world, can double that risk, a new study suggests.

The findings highlight the potential impact of these psychosocial factors on brain health, said lead author Susan Everson-Rose, PhD, associate professor, medicine, University of Minnesota, Minneapolis. "Intuitively, you might think it's true, but it provides empirical support for that."

Physicians are typically focused on traditional risk factors, for example, whether a patient smokes or has high blood pressure. "This study shows that It's also important to pay attention to these psychological factors and know that they can have a negative impact on health," said Dr. Everson-Rose.

The study was published online July 10 in Stroke.

MESA Study
While prior research has linked hostility ? as well as depression and stress ? to cardiovascular disease, this study looked specifically at stroke and transient ischemic attack (TIA). "To my knowledge, other studies have not evaluated hostility in relation to stroke risk, so I think it's the first study to extend these psychosocial findings to that measure or construct," she said.

Researchers used data from the Multi-Ethnic Study of Atherosclerosis (MESA), a longitudinal study of risk factors for clinical and subclinical cardiovascular disease in 6749 adults at 6 centers: Baltimore, Maryland; Chicago, Illinois; St. Paul, Minnesota; Los Angeles, California; New York City, New York; Forsyth County, North Carolina.

The analysis included participants who were free of cardiovascular disease at baseline. The cohort was 53% female, 38.5% non-Hispanic white, 27.8% black, 11.8% Chinese, and 21.9% Hispanic. They ranged in age from 45 to 84 years. Median duration of follow-up was 8.5 years.

Stroke was defined as a rapid onset of documented focal neurologic deficits lasting 24 hours or until death and, if less than 24 hours, with imaging evidence of a clinically relevant lesion. TIA was defined as a documented focal neurologic deficit lasting 30 seconds to 24 hours and without imaging evidence of a clinically relevant lesion or without imaging completed.

Study participants filled out standard questionnaires in their native language. Ongoing stress in 5 domains (their own health, health problems of loved ones, job or ability to work, relationships, and finances) was measured with the Chronic Burden Scale.

Researchers assessed depression with the Center for Epidemiology Studies Depression Scale (CES-D), anger with the Spielberger Trait Anger scale, and hostility with the Cook-Medley Hostility Scale.

During the study, there were 147 strokes (82.3% ischemic, 14.3% hemorrhagic, and 3.4% unspecified) and 48 TIAs. Researchers used a combined outcome of stroke/TIA.

Cynical Approach
After adjustment for for race, sex, age, education, and site, each 1 point higher score for depression (hazard ratio
, 1.03; 95% confidence interval [CI], 1.01 - 1.04), chronic stress (HR, 1.19; CI, 1.05 - 1.34), and hostility (HR, 1.10; 95% CI, 1.01 - 1.19) was related to increased risk for stroke or a TIA. The associations remained significant after further adjustments. Anger was not significantly related to risk for stroke/TIA (P > .10).

There were statistically significant gradients of increasing stroke risk for depressive symptoms, chronic stress, and hostility. Those with the highest scores for CES-D, chronic stress, and hostility were at 1.5- to more than 2-fold increased risk of stroke or TIA compared with those with the lowest scores in the model that adjusted for age, race, sex, education, and study site.

In a model that also adjusted for systolic blood pressure, alcohol use, smoking status, physical activity, body mass index, and use of antihypertensive drugs, HRs were diminished but remained significant.

Hostility had the highest hazard ratios (2.22 in the first model and 2.00 in the second). According to Dr. Everson-Rose, the hostility score measures how people frames their world. "It looks at how much of a negative outlook you have on the world, or if you have a cynical approach to life."

The researchers did subgroup analyses (age, sex, and race-ethnicity) but found no significant differences. "But we don't think it can be considered definitive because the numbers of events were so small," said Dr. Everson-Rose.

The underlying mechanisms linking stress and negative emotions to increased stroke risk could involve activation of the hypothalamic-pituitary-adrenal axis, endothelial dysfunction, or inflammation. In this study, other than the traditional risk factors, researchers assessed markers of inflammation (C-reactive protein, fibrinogen, and interleukin-6) and a marker of subclinical cardiovascular disease (carotid artery intima medial thickness).

"None of those factors actually explained away this risk," commented Dr. Everson-Rose. "So I'm not really sure what the mechanism is; it's an area open for further research."

To identify these risky psychosocial risk factors, Dr. Everson-Rose suggests physicians might consider increased screening using easy-to-use questionnaires; if the scores indicate high levels of depression, stress, or negative emotions, physicians could offer information on stress management, relaxation techniques, and other resources, said Dr. Everson-Rose.

Identify, Modify Risk
For a comment, Medscape Medical News, reached Philip Gorelick, MD, professor, translational science and molecular medicine, Michigan State University, and Medical Director of Hauenstein Neuroscience Center, Grand Rapids.

"The study is very good because it was carried out prospectively, among a number of different race-ethnic groups, and by a very credible and well-known group of investigators," said Dr. Gorelick.

The paper "looks at a number of psychiatric symptoms, including depressive symptoms, hostility, stress, and anger and 3 out of 4 turn out to increase your risk of stroke or TIA in these middle-age and older adults," he added.

"The key message here is that we have to start thinking more about these neuro-psychiatric and neuro-behavioral symptoms, especially in middle age and as we age, and how we might consider modification of these symptoms to determine if that can reduce the risk of cardiovascular disease, including stroke."

Dr. Gorelick agreed that the relatively small number of strokes and TIAs makes it difficult to do subgroup analysis in relation to race and ethnicity. "It's possible that one of these groups was driving the data and we can't know that for sure because of the small numbers; once you divide the 195 strokes among the several race-ethnic groups, you are just not going to know for sure."

As well, said Dr. Gorelick, researchers don't know how many participants were practicing coping strategies ? for example, counseling, relaxation, mindfulness, or other relaxation strategies ? that could have modified the results.
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