In a study of 1,228 nonfatal acute MIs, only 5% appeared to be triggered by exercise. And in a classic study from the 1980s, when the management of patients with acute MI was much less sophisticated and effective than today, data obtained from 167 randomly chosen cardiac rehab programs demonstrated that there was one acute MI per 300,000 supervised exercise hours, one cardiac arrest per 112,000 exercise hours, and one death per 800,000 exercise hours (JAMA 1986;256:1160-3).
The mechanisms through which depression and other forms of psychologic stress boost the risk of secondary cardiac events are thought to include increased platelet reactivity, systemic inflammation, sympathetic activation of the autonomic nervous system, endothelial dysfunction, and increased circulating catecholamines.
Robert M. Carney, Ph.D., pointed out that depression is not only the number-two cause of early death and disability in industrialized nations, but the prevalence of major depression in the months following an acute coronary syndrome has been pegged at 12%-23% in various studies, with another 15%-27% of ACS patients having minor depression.
Thus, close to half of all ACS patients experience significant depressive symptoms (Am. J. Med. 2008;121:S20-7), according to Dr. Carney, professor of psychiatry at Washington University in St. Louis.
What’s more, there is persuasive evidence to show that depression in patients who have experienced an acute coronary syndrome is associated with increased mortality. Dr. Carney cited a recent meta-analysis covering the last 25 years of research on depression and heart disease, which concluded that post-MI depression was independently associated with a 2.7-fold increased likelihood of cardiac mortality and a 1.6-fold increase in cardiac morbidity (Gen. Hosp. Psychiatry 2011;33:203-16).
Although several randomized trials have demonstrated that exercise can reduce depression in CHD patients, there is as yet no randomized trial evidence demonstrating that treating depression actually improves survival in patients with heart disease.
Dr. Carney calls this "the Holy Grail of behavioral psychology." He believes this goal has proved elusive to date because depression is often a remitting and relapsing disorder, and the standard antidepressant therapies, whether pharmacologic or psychotherapies, are "fairly modest" in their effects. The randomized trial data suggest exercise training is in the same efficacy ballpark.
"Exercise appears to be doing about as well as antidepressant drugs or some of the psychotherapies, but it’s not doing a whole lot better," Dr. Carney asserted. "It seems clear to me that monotherapy for depression is often insufficient, both in psychiatric patients and in CHD."
There is, however, some intriguing evidence to suggest that exercise training might be particularly effective in patients whose depression doesn’t respond to traditional antidepressant therapies, the psychologist said. For example, Scottish investigators took 86 primary care patients with major depressive disorder unresponsive to at least 6 weeks of an adequately dosed antidepressant drug and randomized them to a combined endurance and weight-training exercise program or a group health education control group. The two groups met twice weekly for 10 weeks, at which point at least a 30% improvement in HAM-D scores had occurred in 55% of the exercise group and in 33% of controls (Br. J. Psychiatry 2002;180:411-5).
For this reason, Dr. Carney proposed that the next large, multicenter, NIH-sponsored clinical trial testing the hypothesis that treating depression in CHD patients improves survival should include an exercise training arm. But not exercise as monotherapy; instead, exercise should be employed as part of a combination treatment or augmentation strategy, or perhaps in a sequential stepped-care regimen for initial nonresponders.
The approach he advocates is modeled on the stepped-care approach that proved highly effective in the landmark randomized, multicenter Sequential Treatment Alternatives to Relieve Depression (STAR*D) trial. In step 1 of STAR*D, the remission rate with antidepressant monotherapy was 33%; in step 2, with the addition of a second antidepressant or a switch to a different one, the cumulative remission rate climbed to 53% (Am. J. Psychiatry 2006;163:1905-17).
Exercise training as part of combination antidepressant therapy in patients with CHD is attractive for several reasons. Not only may it be more effective than monotherapy, but it confers numerous cardiovascular and general health benefits. And it avoids drug-drug interactions.
"I think that’s a really important consideration in cardiac patients, who often are on 8, 10, 12 different drugs. And SSRIs in particular seem to interact with other drugs," Dr. Carney said.
Dr. Lavie and Dr. Carney reported having no financial conflicts.