Stroke Survival May Hinge On Depression Treatment

A new study is confirming the strong association between stroke and depressive symptoms and is cementing the association between a fatal stroke and those symptoms. Intriguingly, the study found the association to be stronger than that between fatal stroke and either high cholesterol or smoking.

The new analysis comes from the Multiple Risk Factor Intervention Trial (MRFIT), sponsored by the National Heart, Lung and Blood Institute. Findings appear in the January issue of the American Heart Association's journal, Stroke.

The analysis also indicated that the association is not limited to more severe levels of depressive symptoms, such as those indicative of major depressive disorder. The researchers found that any level of depressive symptoms may increase the risk of dying after a stroke.

“Our results say, if you actually look at just the lowest quintile [of depressive symptoms] and you go up one quintile, there's no significant effect,” said Brooks Gump, Ph.D., an associate professor of psychology at the State University of New York at Oswego, and lead author of the report.“ It's more of an association across all levels of depressive symptoms. As you become more depressed, your risk progressively increases. There is a linear association between severity of depressive symptoms and increasing risk of stroke mortality.”

Nearly 13,000 men aged 35 to 57 at entry into the study were followed for at least six years, the length of the original MRFIT study.

Each patient's risk of coronary heart disease (CHD) was judged to be elevated due to multiple risk factors, including elevated blood pressure, blood cholesterol levels, and/or smoking. Survivors at the end of the study were then followed for an additional 18 years. A subset of the original group of men enrolled in the trial was administered the Center for Epidemiologic Studies Depression (CES-D) scale during the sixth year of the study. Those 11,216 men were used in the analysis of the association of depressive symptoms with stroke.

The researchers found that depressive symptoms of any level were associated with a significantly higher risk of mortality from any cause, including cardiovascular disease. More specifically, depressive symptoms were associated with stroke mortality but not with death from coronary heart disease—a finding that contrasts with previous research.

“The sample size here was very large,” Gump told Psychiatric News, “and the sample was very well controlled. We had a lot of [statistical] power to detect differences within the group.”

Gump said his team did initially find an association between CHD and depressive symptoms before they controlled for confounding variables. The analysis controlled for age, assignment to a MRFIT intervention group, race, educational attainment, smoking both at entry to the study and at year six, patients' average systolic blood pressure over the six years, alcohol consumption, and fasting cholesterol levels. They also controlled for occurrence of nonfatal cardiovascular events during the trial.

“After we controlled for those covariates, there was no longer a significant association [between depressive symptoms and CHD],” Gump explained. “Whereas the association with stroke, and more specifically death following a stroke, remained significantly different.”

Gump believes one of the reasons prior research has found statistically significant associations between depression and heart disease is that the studies were not adequately controlled.

“Ours is only one paper,” Gump said, “but I think that future studies associating the two have to be well controlled for all possible confounds. And they need to consider stroke separately [from other forms of cardiovascular disease, especially coronary heart disease],” he stressed.

“Even then, we can't say that the depression is causing the stroke,” he cautioned. “I do think though that there is a strong possibility that there is some sort of micro-stroke phenomenon that is subclinical—silent strokes. And it is possible that those silent strokes are precipitating the subsequent depression, and the end result, mortality.”

Alexander Glassman, M.D., a clinical professor of psychiatry at Columbia University, noted that the study “adds to a long list of studies implicating depression in the progression of vascular disease.” Glassman, who led the Sertraline Antidepressant Heart Attack Randomized Trial (SADHART)—a multicenter trial that looked at the effect of sertraline (Zoloft) treatment for depressive symptoms following a heart attack—told Psychiatric News that depression has been linked with both stroke and coronary disease. “Taking all the studies together makes a very compelling case [for a link between] depression and vascular disease.”

An abstract of “Depressive Symptoms and Mortality in Men: Results From the Multiple Risk Factor Intervention Trial” is posted online at<http://stroke.ahajournals.org/cgi/content/abstract/36/1/98>.▪