From Heartwire — a professional news service of WebMD

November 26, 2008 — Researchers who set out to pick apart the bonds that link depression and cardiovascular disease (CVD) say that health behaviors and not complex biological processes largely account for the increased risk of cardiac events in people with depression [1]. Physical inactivity, in particular, likely accounts for the bulk of the risk, Dr Mary A Whooley (VA Medical Center, San Francisco, CA) and colleagues write in the November 26, 2008 issue of the Journal of the American Medical Association.

The Heart and Soul Study looked at over 1000 people with stable coronary heart disease, followed for almost five years, measuring depressive symptoms at baseline in relation to subsequent heart failure, myocardial infarction (MI), stroke, transient ischemic attack, or death.

Whooley explained to heartwire that while depression has long been known to increase the risk of heart disease, the candidate mechanisms had not previously been. "There's been a lot of interest in physiological consequences of depression, like elevated norepinephrine, elevated cortisol, low heart-rate variability, and platelet activation, but there hasn't been as much focus on the behavioral mediators, although they certainly have been suggested by previous studies. Surprisingly, we found that the fancy physiological mediators really were not explaining the association and that it seemed to be all about health behaviors."

According to Whooley, depressed patients were less likely to take their medications as prescribed, less likely to exercise, and more likely to smoke. "And after you accounted for those health behaviors, the association between depression and CVD went away. So we concluded that link between depression and heart disease is largely explained by these health behaviors."

Good, but challenging news

As with other studies, Whooley et al's analysis showed a clear link between depression and cardiovascular (CV) events. Of the 341 events that occurred over the 4876 person-years of follow-up, the age-adjusted rate of events was 10% among the 199 individuals with depressive symptoms and only 6.7% among the 818 subjects without depressive symptoms (p=0.002). That translated into a 31% increased risk of cardiovascular events in depressed subjects, after adjustment for comorbidities and disease severity.

If biological mediators were factored into the analysis—things like use of antidepressant drugs, heart-rate variability, levels of serotonin and omega-3s, or 24-hour excretion of norepinephrine and cortisol—the effect size for depressive symptoms on cardiovascular events did not substantially change. However, when behavioral factors such as adherence to medication, smoking status, and most strikingly physical activity were factored in, the association between depressive symptoms and cardiovascular events was no longer statistically significant.

"This is good news in that these are modifiable and it's cheap to get people to exercise and to take their medications; the more challenging news is that it's very hard to change behaviors," Whooley commented. "We can't just give people a medication that will magically lower their norepinephrine or cortisol, we have to start behavioral interventions, and those are notoriously difficult."

Whooley also acknowledged that it doesn't matter whether patients first grew depressed due to lack of physical exercise or stopped exercising when they became depressed. "Very likely it's a vicious cycle and the association is bidirectional," she said. "In our opinion, it doesn't really matter whether it's the chicken or the egg because the bottom line is the same—if you increase exercise in these patients, you're going to reduce their risk of heart disease. But the thing to remember about depressed patients is that they are that much less motivated to do things, so it takes extra effort to get them to exercise, take their medications, and stop smoking."

The Heart and Soul results may help explain the failure of a number of high-profile trials looking at whether use of antidepressant medication in depressed subjects could improve cardiovascular outcomes. Whooley et al's results "open up another potential intervention," she said. Indeed, the Understanding Prognostic Benefits of Exercise and Antidepressant Therapy (UPBEAT) study, still under way, is comparing antidepressants with an exercise intervention in improving cardiovascular risk factors. "It won't be looking at whether we can actually prevent events, but rather changes in inflammation and things like that. But it is the next step in the right direction," Whooley said.

Her group is also continuing to investigate the association between physical activity level and heart disease in depressed subjects, with the ultimate aim of developing an intervention that might be able to reduce the risk of events in people with cardiovascular disease.

Source

1. Whooley MA, de Jonge P, Vittinghoff E, et al. Depressive symptoms, health behaviors, and risk of cardiovascular events in patients with coronary heart disease. JAMA 2008;300:2379-2388.

The complete contents of Heartwire , a professional news service of WebMD, can be found at www.theheart.org, a Web site for cardiovascular healthcare professionals.

Clinical Context

Pearls for Practice

• In patients with underlying CV disease, depressive symptoms are associated with increased risk for CV events.
• The association between depression and CV risk is dose-dependent and largely accounted for by physical inactivity.

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