Physical Activity Key to Cardiovascular Impact of Depression

By Crystal Phend
SAN FRANCISCO, 01 dez 2008-- For coronary heart disease patients, depression may be associated with worse outcomes, primarily because it tends to curtail physical activity, researchers found. Those cardiac patients who had symptoms of depression had a 31% higher rate of cardiovascular events, after controlling for comorbidities and disease severity (P=0.04), reported Mary A. Whooley, M.D., of the University of California San Francisco, and colleagues in the Nov. 26 issue of the Journal of the American Medical Association. Earlier studies had suggested biological factors like norepinephrine, inflammation, and cortisol could be responsible, but these captured surprisingly little of the effect in their prospective cohort study, Dr. Whooley said. Rather, adjustment for health behaviors such as physical inactivity and medication adherence eliminated the link (P=0.75). This is good news for physicians and patients Dr. Whooley said.
"Exercise training can improve both depressive symptoms and markers of cardiovascular risk," they wrote.
The downside, though, is that lasting changes in behavior, particularly with regard to exercise, are difficult, Dr. Wholley added.
But even for patients who are able to achieve improvements, it's not been proven that the cardiovascular risk associated with depression would disappear, Dr. Whooley said.
Given the benefits of physical activity across the board, though, she said physicians should still find ways to motivate their patients to make these changes.
Dr. Whooley and her colleagues conducted the prospective Heart and Soul Study among 1,017 patients seen for stable coronary disease at 12 outpatient clinics in the San Francisco area.
Among them, 19.6% had depressive symptoms with a self-reported Patient Health Questionnaire score of at least 10 points.
During about 4.8 years of follow-up, these depressed patients had a significantly higher annual rate of cardiovascular events after age adjustment (10.0% versus 6.7%, hazard ratio 1.50, 95% confidence interval 1.16 to 1.95, P=0.002).
Adjustment for comorbid conditions and cardiac disease severity attenuated the association with cardiovascular events -- heart failure, MI, stroke, transient ischemic attack, or death (HR 1.31, P=0.04).
Higher depressive symptom scores increased cardiovascular events in an apparent dose-dependent relationship.
With each standard deviation increase in depressive symptom score (5.5-points) cardiovascular event rates rose 15% (HR 1.15, P=0.01) after adjustment for age, comorbidities, and left ventricular ejection fraction.
Additional adjustment for inflammation as indicated by C-reactive protein levels also reduced the strength of the association between depression and events in this population (HR 1.24, P=0.12).
However, the most substantial factor accounting for the association was physical activity. Adjustment for it attenuated the link between depression and cardiovascular events by 31.7%.
Altogether, adjustment for physical inactivity, medication adherence, smoking, and other behavioral factors eliminated the association between depressive symptoms and cardiovascular events.
But physical inactivity remained predictive of a 44% elevation in cardiovascular events (HR 1.44, P=0.002) even after adjusting for depressive symptoms, comorbidities, ejection fraction, inflammation, smoking, and medication adherence.
As a more objective measure of physical activity, exercise capacity reduced the effect of depression on cardiovascular events to a similar degree, eliminating its significance (HR 0.96, P=0.79).
Although the study could not determine causality, the researchers noted that the association is "almost certainly bidirectional" with mutually reinforcing exacerbation.
Factors with little impact on the association included use of selective serotonin reuptake inhibitors or tricyclic antidepressants, heart rate variability, levels of serotonin and omega-3 fatty acids, and 24-hour excretion of norepinephrine and cortisol.
Generalizability of the findings may be limited, the researchers said, because most participants were older men, half of whom were from VA Medical Centers.
Also, they noted, the study could not determine the association between depression and events in healthy patients or those with acute coronary syndrome.
The study was supported by the VA Epidemiology Program; the VA Health
Research and Development Service Career Development Program; the National Heart, Lung, and Blood Institute; the American Federation for Aging Research; the Robert Wood Johnson Foundation; the Ischemia Research and Education Foundation; and the Nancy Kirwan Heart Research Fund.
The researchers reported no conflicts of interest.
Primary source: Journal of the American Medical AssociationSource reference:Whooley MA, et al "Depressive symptoms, health behaviors, and risk of cardiovascular events in patients with coronary heart disease" JAMA 2008; 300: 2379-2388.