Recent studies conducted at the San Francisco VA Medical Center suggest two possible mechanisms for the widely recognized link between depression and adverse outcomes in patients with coronary heart disease: lack of adherence to medication regimens and increased levels of norepinephrine, a stress hormone.
"Patients with depression are more likely to suffer heart attacks and heart failure, and more likely to die of heart disease, and no one knows why," notes Mary Whooley, MD, a staff physician at SFVAMC and the principal investigator of both studies. "These results give us two intriguing clues: one behavioral, one biological."
One study looked at the association between depression and self-reported medication adherence in 940 patients with stable coronary heart disease, 204 of whom were diagnosed as depressed. Fourteen percent of the depressed patients reported not taking their medications as prescribed over a 30-day period, compared with 5 percent of the non-depressed patients.
The study appears in the November 28 issue of Archives of Internal Medicine.
Another study examined 24-hour urinary norepinephrine levels in 598 coronary disease patients, 106 of whom had depressive symptoms. A total of 9.4 percent of the depressed participants had a urinary norepinephrine value above the normal range, compared with 3.3 percent of the non-depressed participants. In addition, the more depressive symptoms a participant had, the higher the participant's norepinephrine levels.
This paper appears in the November 2005 issue of the American Journal of Psychiatry.
Neither study indicates a mechanism for adverse coronary outcomes "because we were only looking at cross-sectional data," stresses Whooley, who is also an associate professor of medicine at the University of California, San Francisco.
However, she says, both papers suggest further avenues of research.
The medication-adherence study raises the possibility that because they're depressed, patients simply aren't doing what they're supposed to do to take care of themselves, and this in turn implies a potential treatment, according to Whooley. "If you get rid of the depression, you might get rid of the non-adherence."
The norepinephrine study, on the other hand, suggests that depression could make heart disease patients "more vulnerable to the ill effects of elevated stress hormones," she speculates. While there was no association between norepinephrine levels and baseline severity of heart disease in the current study, "that doesn't necessarily mean that patients with elevated norepinephrine won't have worse outcomes over time," she cautions.
The next thing to do, says Whooley, is "figure out which of these factors - behavioral or biological - accounts for increased risk of heart disease, or whether it's some combination of the two. And that's what we're working on now."
Whooley and her co-authors are conducting studies that will investigate whether medication non-adherence or elevated norepinephrine actually predict increased risk of heart disease over time.
Participants in both of the current studies are enrolled in the Heart and Soul Study, an ongoing, multi-center, prospective cohort study of psychosocial factors and health outcomes in patients with coronary heart disease that is in its fifth year. The study is sponsored by the Department of Veterans Affairs Epidemiology Program, the Robert Wood Johnson Foundation, and the American Federation for Aging Research.
"The overall goal of the Heart and Soul Study is to try to understand why depression predicts adverse cardiovascular outcomes," explains Whooley, who is the study's principal investigator. "Eventually, we hope to help these patients with the treatment they deserve, and by doing so, decrease the overall burden of death from cardiac disease."
Co-authors of the medication study include Anil Gehi, MD, and Donald Haas, MD, of the Mount Sinai School of Medicine, New York, and Sharon Pipkin, MPH, of the San Francisco Department of Public Health.
The medication study was funded by grants from the U.S. Department of Veterans Affairs and the Robert Wood Johnson Foundation, plus grants from the American Federation for Aging Research and the Nancy Kirwan Heart Research Fund that were administered by the Northern California Institute for Research and Education.
Co-authors of the norepinephrine study include Christian Otte, MD, of the University Hospital Hamburg-Eppendorf in Germany; Thomas C. Neylan, MD, of SFVAMC and UCSF; Sharon S. Pipkin, MPH, of SFVAMC, and Warren S. Browner, MD, MPH, of California Pacific Medical Center, San Francisco.
The norepinephrine study was funded by grants from the U.S. Department of Veterans Affairs and the Robert Wood Johnson Foundation, and a grant from the Ischemia Research and Education Foundation that was administered by NCIRE.
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