September 21, 2011 — Patients with depression could be at increased risk for stroke. Results from a new meta-analysis of 28 studies including more than 300,000 patients show a significantly increased risk for stroke and stroke-related mortality among those with depression.

"We were not surprised by the results because previous studies, including our work in this area, have demonstrated that depression increases the risk of obesity, diabetes, and coronary heart disease," lead investigator An Pan, PhD, from the Harvard School of Public Health in Boston, Massachusetts, told Medscape Medical News. "Depression should be considered as an independent risk factor for the future risk of stroke."

Stroke is a leading cause of death and permanent disability, with significant economic losses resulting from functional impairments, Dr. Pan pointed out. Depression is highly prevalent in the general population, and it is estimated that 5.8% of men and 9.5% of women will experience a depressive episode in a 12-month period. The lifetime incidence of depression has been estimated at more than 16% in the general population. The prevalence is thought to be even higher in people with comorbidities such as obesity, diabetes, and hypertension.

The researchers speculate that depression may contribute to stroke through a variety of mechanisms including neuroendocrine and immunological or inflammatory effects. It may also be linked to negative health behaviors such as smoking, poor diet, and physical inactivity.

The results from the meta-analysis appear in the September 21 issue of the Journal of the American Medical Association.

A number of studies have already assessed the association between depression and stroke. A previous meta-analysis focusing on cardiovascular outcomes pooled results from 10 studies and reported a positive association between depression and stroke risk. Since then, many more prospective cohort studies have been published. Investigators say this new meta-analysis describes the association between depression and future risk for stroke.

The investigators identified 8478 stroke cases during a follow-up period ranging from 2 to 29 years. They defined depression by self-reported scales or clinician diagnosis. They found that depression was associated with a 45% increased risk for total stroke, a 55% increased risk for fatal stroke, and a 25% increased risk for ischemic stroke. Depression was not associated with an increased risk for hemorrhagic stroke.

Pooled Adjusted Hazard Ratios for Stroke Risk Associated With Depression

Stroke Hazard Ratio 95% Confidence Interval P Value Total 1.45 1.29 to 1.63 < .001 Fatal 1.55 1.25 to 1.93 .31 Ischemic 1.25 1.11 to 1.40 .34

The corresponding absolute risk difference associated with depression based on the most recent stroke statistics for the United States was estimated to be the highest for total stroke.

Absolute Risk per 100,000 Individuals per Year

Stroke Absolute Risk (Cases) Total 106 Ischemic 53 Fatal 22

Given the high prevalence and incidence of depression and stroke in the general population, Dr. Pan said, the observed association between depression and stroke has clinical and public health importance. "More studies are needed to explore the underlying mechanisms and elucidate the causal pathways that link depression and stroke."

Poststroke Depression: A Misnomer?

In a Medscape Seminar in Neurology , Linda Williams, MD, from the Indiana University School of Medicine in Indianapolis, pointed out the timing of depression in relation to stroke is a critical issue that has not been well studied. "Any depression recognized after a stroke has occurred is termed post-stroke depression, and whether the depressive symptoms predated the stroke is not ascertained."

She points out that more work needs to be done in this area. "Because effective treatments exist but are likely underutilized for depression, this is an important example of an evidence-practice gap to which increased efforts to improve care should be made. Such efforts would likely improve not only patient symptoms but may also decrease stroke risk, influence stroke functional recovery, decrease mortality, and reduce post-stroke health care utilization."

This study was supported by the National Institutes of Health. The investigators have disclosed no relevant financial relationships.

JAMA. 2011;306:1241-1249. Abstract