New data published in the Journal of the American College of Cardiology suggest that relatively healthy women with severe depression are at increased risk of cardiac events, including sudden cardiac death (SCD) and fatal coronary heart disease (CHD). Researchers found that much of the relationship between depressive symptoms and cardiac events was mediated by cardiovascular disease risk factors, such as high blood pressure, high cholesterol and smoking. 

The researchers prospectively studied 63,469 women from the Nurses Health Study who had no evidence of prior heart disease or stroke during follow-up between 1992 and 2004. Self-reported symptoms of depression and use of antidepressant medication were used as measures of depression. To best identify those with clinical depression, researchers specifically examined women with the most severe symptoms defined by a validated 5-point mental health index score of less than 53 or regular antidepressant use. 

The study found that women with more severe depressive symptoms or those who reported taking antidepressants were at higher risk for SCD and fatal CHD. In particular, women with clinical depression were more than twice as likely to experience sudden cardiac death. Surprisingly, this risk was associated more strongly with antidepressant use than with depressive symptoms. 

"It's important for women with depression to be aware of the possible association between depression and heart disease, and work with their health care providers to manage their risk for coronary heart disease," says William Whang, M.D., M.S., Division of Cardiology, Columbia University Medical Center, and lead investigator of the study. "A significant part of the heightened risk for cardiac events seems to be explained by the fact that coronary heart disease risk factors such as high blood pressure, diabetes, elevated cholesterol, and smoking were more common among women with more severe depressive symptoms." 

"These data indicate the link between depression and serious heart rhythm problems may be more complex than previously thought," says Sanjiv M. Narayan, M.D., F.A.C.C., University of California, San Diego, who co-authored the accompanying editorial with colleague, Murray Stein, M.D. "It raises the question of whether this association may have something to do with the antidepressant drugs used to treat depression."

Both Drs. Whang and Narayan stress that although the relationship between antidepressant medicines and SCD merits further investigation to determine whether antidepressant medications directly increase the risk for heart rhythm disorders, at present the benefits of appropriately prescribed antidepressants outweigh the risk of sudden cardiac death. There was no relationship between antidepressant use and fatal CHD or nonfatal heart attack.

"We can't say antidepressant medications were the cause of higher risk of sudden cardiac death. It may well be that use of antidepressants is a marker for worse depression," adds Dr. Whang. "Our data raise more questions about the mechanisms by which depression is associated with arrhythmia and cardiac death." 

Plausible explanations for the link between depression and SCD may include autonomic dysfunction, higher resting heart rates and reduced heart rate variability, according to Dr. Whang. Researchers also found an association with nonfatal MI, but this became borderline non-significant when adjusted for multiple other CHD risk factors.

Still, these study findings reinforce the need for patients with depression to be monitored closely for risk factors for coronary heart disease, since management of these risk factors can reduce the risk for mortality from coronary heart disease and sudden cardiac death. 

Dr. Whang reports no conflict of interest.