Exercise Reaps Double Benefits in Post-MI Depression

NEW ORLEANS – Exercise training is the sole therapy that simultaneously addresses two of the major risk factors for secondary cardiovascular events in patients with known coronary heart disease: depression and sedentary lifestyle.

Despite this, formal cardiac rehabilitation programs, which as a matter of course place strong emphasis upon exercise training, are tremendously underutilized.

Photo courtesy Ochsner Health System

"My estimation is that only 5%-7% of CHD patients who are candidates actually attend a cardiac rehabilitation program. Even in the Medicare population – and Medicare covers cardiac rehabilitation – only 13% of post-MI patients, for example, attend cardiac rehabilitation," said Dr. Carl J. Lavie, a cardiologist who is medical director of cardiac rehabilitation and the exercise laboratories at the Ochsner Heart and Vascular Institute, New Orleans.

Because cardiac rehab for secondary prevention in CHD patients has been shown to reduce mortality, placebo-controlled randomized trials are no longer possible. But Dr. Lavie and Dr. Richard V. Milani, who is also with Ochsner, showed in a series of 522 consecutive patients enrolled in cardiac rehab that the prevalence of depression, as defined by a score greater than 6 on the well-validated Kellner Symptom Questionnaire, dropped from 17% at baseline to 6% upon completing the program. That’s a 63% reduction.

Moreover, at 5 years of follow-up, all-cause mortality was 22% among patients who remained depressed post-cardiac rehab, compared with 5% in nondepressed patients. And when the investigators analyzed their data based upon change in peak oxygen – a handy yardstick for cardiorespiratory fitness – during cardiac rehab and exercise training, they found it didn’t take much of a gain in VO₂ max to obtain a significant mortality benefit. Five-year all-cause mortality was 6% in patients who achieved less than a 10% gain in VO₂ max, compared with 4% in those with a more marked improvement in peak oxygen consumption and 15% in those with a VO₂ loss (Am. J. Med. 2007;120:799-806).

More recently, the investigators evaluated the impact of exercise training and depression on survival in 189 patients with heart failure and a mean left ventricular ejection fraction of 35%. Among the 151 patients who completed a standard 12-week, 36-session formal cardiac rehab education and exercise training program, the prevalence of depression symptoms fell by 40%, from 22% at baseline to 13%. During a mean 4.6 years of follow-up, all-cause mortality in depressed patients with heart failure who didn’t complete the program was 44%, compared with 18% in depressed patients who did. Among patients depressed at baseline who remained so after completing cardiac rehab, long-term mortality was fourfold greater than in those whose depression resolved with rehab: 43% vs. 11% (Am. J. Cardiol. 2011;107:64-8).

So why isn’t cardiac rehab prescribed as often as, say, daily aspirin or statin therapy for secondary prevention?

"I still run into a tremendous number of internists and family physicians and cardiologists who haven’t totally bought into the role of psychologic stress in cardiovascular disease. And I think in your field of psychology, there’s probably a whole lot who haven’t bought into the importance of exercise training and cardiorespiratory fitness in preventing what is certainly the major cause of morbidity and mortality in the western world," Dr. Lavie declared at the annual meeting of the Society of Behavioral Medicine.

Dr. Lavie has been studying the antidepressant effects of cardiac rehab and exercise training for 20 years. At the meeting, he got together with prominent behavioral psychologists having lengthy experience in clinical trials for depression to assess the current standing of exercise training for secondary prevention in CHD and how best to advance the field.

For his physician colleagues who still question the role of psychologic stress in CHD, Dr. Lavie is quick to point to what he considers the most persuasive evidence: the landmark INTERHEART study.

"It really clinches things for many people who were skeptics," the cardiologist observed.

INTERHEART, led by Dr. Salim Yusuf of McMaster University in Hamilton, Ont., evaluated CHD risk factors in 11,119 MI patients and 13,648 age- and gender-matched controls at 262 centers in 52 countries. Among the nine major modifiable cardiovascular risk factors, psychologic stress ranked only behind serum lipids and smoking in importance. Indeed, psychologic stress accounted for one-third of the attributable risk of CHD (Lancet 2004; 364: 953-62).

Many physicians remain concerned about the transient increase in risks of acute MI and sudden cardiac death during physical exertion, but this issue has been blown way out of proportion, in Dr. Lavie’s view.

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.

NEW ORLEANS – Exercise training is the sole therapy that simultaneously addresses two of the major risk factors for secondary cardiovascular events in patients with known coronary heart disease: depression and sedentary lifestyle.

Despite this, formal cardiac rehabilitation programs, which as a matter of course place strong emphasis upon exercise training, are tremendously underutilized.

Photo courtesy Ochsner Health System

"My estimation is that only 5%-7% of CHD patients who are candidates actually attend a cardiac rehabilitation program. Even in the Medicare population – and Medicare covers cardiac rehabilitation – only 13% of post-MI patients, for example, attend cardiac rehabilitation," said Dr. Carl J. Lavie, a cardiologist who is medical director of cardiac rehabilitation and the exercise laboratories at the Ochsner Heart and Vascular Institute, New Orleans.

Because cardiac rehab for secondary prevention in CHD patients has been shown to reduce mortality, placebo-controlled randomized trials are no longer possible. But Dr. Lavie and Dr. Richard V. Milani, who is also with Ochsner, showed in a series of 522 consecutive patients enrolled in cardiac rehab that the prevalence of depression, as defined by a score greater than 6 on the well-validated Kellner Symptom Questionnaire, dropped from 17% at baseline to 6% upon completing the program. That’s a 63% reduction.

Moreover, at 5 years of follow-up, all-cause mortality was 22% among patients who remained depressed post-cardiac rehab, compared with 5% in nondepressed patients. And when the investigators analyzed their data based upon change in peak oxygen – a handy yardstick for cardiorespiratory fitness – during cardiac rehab and exercise training, they found it didn’t take much of a gain in VO₂ max to obtain a significant mortality benefit. Five-year all-cause mortality was 6% in patients who achieved less than a 10% gain in VO₂ max, compared with 4% in those with a more marked improvement in peak oxygen consumption and 15% in those with a VO₂ loss (Am. J. Med. 2007;120:799-806).

More recently, the investigators evaluated the impact of exercise training and depression on survival in 189 patients with heart failure and a mean left ventricular ejection fraction of 35%. Among the 151 patients who completed a standard 12-week, 36-session formal cardiac rehab education and exercise training program, the prevalence of depression symptoms fell by 40%, from 22% at baseline to 13%. During a mean 4.6 years of follow-up, all-cause mortality in depressed patients with heart failure who didn’t complete the program was 44%, compared with 18% in depressed patients who did. Among patients depressed at baseline who remained so after completing cardiac rehab, long-term mortality was fourfold greater than in those whose depression resolved with rehab: 43% vs. 11% (Am. J. Cardiol. 2011;107:64-8).

So why isn’t cardiac rehab prescribed as often as, say, daily aspirin or statin therapy for secondary prevention?

"I still run into a tremendous number of internists and family physicians and cardiologists who haven’t totally bought into the role of psychologic stress in cardiovascular disease. And I think in your field of psychology, there’s probably a whole lot who haven’t bought into the importance of exercise training and cardiorespiratory fitness in preventing what is certainly the major cause of morbidity and mortality in the western world," Dr. Lavie declared at the annual meeting of the Society of Behavioral Medicine.

Dr. Lavie has been studying the antidepressant effects of cardiac rehab and exercise training for 20 years. At the meeting, he got together with prominent behavioral psychologists having lengthy experience in clinical trials for depression to assess the current standing of exercise training for secondary prevention in CHD and how best to advance the field.

For his physician colleagues who still question the role of psychologic stress in CHD, Dr. Lavie is quick to point to what he considers the most persuasive evidence: the landmark INTERHEART study.

"It really clinches things for many people who were skeptics," the cardiologist observed.

INTERHEART, led by Dr. Salim Yusuf of McMaster University in Hamilton, Ont., evaluated CHD risk factors in 11,119 MI patients and 13,648 age- and gender-matched controls at 262 centers in 52 countries. Among the nine major modifiable cardiovascular risk factors, psychologic stress ranked only behind serum lipids and smoking in importance. Indeed, psychologic stress accounted for one-third of the attributable risk of CHD (Lancet 2004; 364: 953-62).

Many physicians remain concerned about the transient increase in risks of acute MI and sudden cardiac death during physical exertion, but this issue has been blown way out of proportion, in Dr. Lavie’s view.

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.

NEW ORLEANS – Exercise training is the sole therapy that simultaneously addresses two of the major risk factors for secondary cardiovascular events in patients with known coronary heart disease: depression and sedentary lifestyle.

Despite this, formal cardiac rehabilitation programs, which as a matter of course place strong emphasis upon exercise training, are tremendously underutilized.

Photo courtesy Ochsner Health System

"My estimation is that only 5%-7% of CHD patients who are candidates actually attend a cardiac rehabilitation program. Even in the Medicare population – and Medicare covers cardiac rehabilitation – only 13% of post-MI patients, for example, attend cardiac rehabilitation," said Dr. Carl J. Lavie, a cardiologist who is medical director of cardiac rehabilitation and the exercise laboratories at the Ochsner Heart and Vascular Institute, New Orleans.

Because cardiac rehab for secondary prevention in CHD patients has been shown to reduce mortality, placebo-controlled randomized trials are no longer possible. But Dr. Lavie and Dr. Richard V. Milani, who is also with Ochsner, showed in a series of 522 consecutive patients enrolled in cardiac rehab that the prevalence of depression, as defined by a score greater than 6 on the well-validated Kellner Symptom Questionnaire, dropped from 17% at baseline to 6% upon completing the program. That’s a 63% reduction.

Moreover, at 5 years of follow-up, all-cause mortality was 22% among patients who remained depressed post-cardiac rehab, compared with 5% in nondepressed patients. And when the investigators analyzed their data based upon change in peak oxygen – a handy yardstick for cardiorespiratory fitness – during cardiac rehab and exercise training, they found it didn’t take much of a gain in VO₂ max to obtain a significant mortality benefit. Five-year all-cause mortality was 6% in patients who achieved less than a 10% gain in VO₂ max, compared with 4% in those with a more marked improvement in peak oxygen consumption and 15% in those with a VO₂ loss (Am. J. Med. 2007;120:799-806).

More recently, the investigators evaluated the impact of exercise training and depression on survival in 189 patients with heart failure and a mean left ventricular ejection fraction of 35%. Among the 151 patients who completed a standard 12-week, 36-session formal cardiac rehab education and exercise training program, the prevalence of depression symptoms fell by 40%, from 22% at baseline to 13%. During a mean 4.6 years of follow-up, all-cause mortality in depressed patients with heart failure who didn’t complete the program was 44%, compared with 18% in depressed patients who did. Among patients depressed at baseline who remained so after completing cardiac rehab, long-term mortality was fourfold greater than in those whose depression resolved with rehab: 43% vs. 11% (Am. J. Cardiol. 2011;107:64-8).

So why isn’t cardiac rehab prescribed as often as, say, daily aspirin or statin therapy for secondary prevention?

"I still run into a tremendous number of internists and family physicians and cardiologists who haven’t totally bought into the role of psychologic stress in cardiovascular disease. And I think in your field of psychology, there’s probably a whole lot who haven’t bought into the importance of exercise training and cardiorespiratory fitness in preventing what is certainly the major cause of morbidity and mortality in the western world," Dr. Lavie declared at the annual meeting of the Society of Behavioral Medicine.

Dr. Lavie has been studying the antidepressant effects of cardiac rehab and exercise training for 20 years. At the meeting, he got together with prominent behavioral psychologists having lengthy experience in clinical trials for depression to assess the current standing of exercise training for secondary prevention in CHD and how best to advance the field.

For his physician colleagues who still question the role of psychologic stress in CHD, Dr. Lavie is quick to point to what he considers the most persuasive evidence: the landmark INTERHEART study.

"It really clinches things for many people who were skeptics," the cardiologist observed.

INTERHEART, led by Dr. Salim Yusuf of McMaster University in Hamilton, Ont., evaluated CHD risk factors in 11,119 MI patients and 13,648 age- and gender-matched controls at 262 centers in 52 countries. Among the nine major modifiable cardiovascular risk factors, psychologic stress ranked only behind serum lipids and smoking in importance. Indeed, psychologic stress accounted for one-third of the attributable risk of CHD (Lancet 2004; 364: 953-62).

Many physicians remain concerned about the transient increase in risks of acute MI and sudden cardiac death during physical exertion, but this issue has been blown way out of proportion, in Dr. Lavie’s view.

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.