Depression Strongly Linked to Stroke Risk

Pauline Anderson

May 16, 2013

Middle-aged women with depression are more than twice as likely to have a stroke as those without depression, a new study shows, suggesting the stroke risk in these women is stronger than previously thought.

Because traditional risk factors, such as diabetes and hypertension, accounted for only some of the association, the study authors surmise that a biological mechanism may play a role.

The study results underline the importance of identifying depression as a possible preventable risk factor for stroke, said study author Caroline A. Jackson, PhD, Centre for Longitudinal and Life Course Research, University of Queensland, Brisbane, Australia.

"We're adding to the growing body of evidence which shows there's a strong relationship between mental health and physical health," said Dr. Jackson. "It's important to raise awareness not just among individual patients — men and women — but also among doctors, to make sure that people can access proper treatment and care."

The research is published online May 16 in Stroke.

Other studies have looked at the association of depression and stroke, although most didn't stratify results by age. The Nurses' Health Study found a 30% higher risk for stroke among depressed women, but it included women who were 14 years older than those in the current study.

"Our study wasn't novel in terms of saying that it's possible that there's a relationship between depression and stroke risk; we're saying it's possibly stronger in these younger-aged women."

Dr. Jackson hopes to next use a bigger data set that includes both older and younger participants to clarify whether there's an age interaction for the effect of depression on stroke risk.

Depression Prevalence

The study included 10,547 participants (mean age, 52.5 years), who were enrolled in the population-based Australian Longitudinal Study on Women's Health (ALSWH). The women completed questionnaires in 1998 and every 3 years during the 12-year follow-up.

Researchers determined the prevalence of depression to be 25.1%. Depression was present if women reported taking antidepressant medication or if they scored 10 or more on the Center for Epidemiological Studies Depression scale shortened version (CESD-10).

During follow-up, the women were asked whether they had been diagnosed or treated for stroke in the previous 3 years. Researchers identified deaths and cause of death through linkage with the National Death Index.

Researchers identified 177 first-ever strokes, 5 of which were fatal, giving a stroke prevalence of 1.5%. Of these, 143 were included in the primary analysis, which found that depression was associated with more than a 2-fold greater odds of stroke (odds ratio [OR], 2.41; 95% confidence interval, 1.78 - 3.27; P < .001).

The association lessened but remained statistically significant after adjustment for age, socioeconomic status (SES), lifestyle, and physiologic stroke risk factors (OR, 1.94; 95% CI, 1.37 - 2.74; P < .001).

"When we adjusted for known established stroke risk factors, the odds ratio, or the effect, did attenuate slightly," said Dr. Jackson. "We know it's partly operating through things like hypertension and diabetes but this didn't account for all of the association; there was still almost a doubling of the risk of stroke."

A sensitivity analysis that used alternative definitions of depression came up with similar results, as did an analysis that included missing covariate data.

Although it has been suggested that antidepressants themselves increase stroke risk, possibly via the inhibition of platelet aggregation that increases bleeding risk, the association between depressive symptoms and stroke remained when researchers excluded women taking antidepressants.

Although experts can't pinpoint the exact mechanism through which depression raises stroke risk in middle-aged women, research has linked inflammatory pathways with depression in heart disease, and a similar mechanism may be at play here, said Dr. Jackson.

"One mechanism that has been proposed in terms of cardiovascular disease is that depression has an effect on the vasculature of the body, and could be adversely affecting the blood vessels or the endothelium of the blood vessels."

Depression Overlooked

Unfortunately, depression is underrecognized as a risk factor for stroke, said Dr. Jackson. "When I looked at guidelines and reviews of primary prevention of stroke, I couldn't find any mention of depression in some pretty key documents, so I think it has been overlooked."

A limitation of the study was that stroke was self-reported Also, the study didn't collect information on stroke type, and although a sensitivity analysis using alternative definitions of depression showed robust results, depressive symptoms identified using the CESD-10 in a self-administered questionnaire could have introduced errors in ascertaining depression, the researchers note.

Invited to comment, Ralph Sacco, MD, professor and chair, neurology, University of Miami, Florida, and spokesperson for the American Heart Association, said the study was important because of its large size, its focus on middle-aged women, and its finding of a very robust effect of depression on stroke risk.

Dr. Sacco agreed that a vascular mechanism may be involved somehow in the link between depression and stroke, and that risk factors may overlap. "The same risk factors that lead to stroke — high blood pressure, diabetes, heart disease — may also affect the brain and affect the risk of depression."

Although the authors did factor in these risk factors in their analysis, Dr. Sacco added, "if there is, let's say, a common causal connection between what we can call vascular depression and vascular stroke, the adjustment may not handle that."

The authors have disclosed no relevant financial relationships.

Stroke. Published online May 16, 2013.


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