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Harvard Commentaries
Harvard Commentaries
Reviewed by the Faculty of Harvard Medical School

Minding Your Mind Minding Your Mind

Heart Disease & Depression -- A Two-Way Street?

October 14, 2012

By Michael Craig Miller M.D.

Harvard Medical School

When a cardiologist (heart doctor) asks how a patient is feeling, the question usually refers to the body. But he or she should ask about moods and emotions, too. The answer can offer important information about a person's general and cardiovascular health.

Mental and physical health were once considered separate entities. Now we know they are profoundly connected. The relationship between depression and heart disease is a good example:

  • People who are depressed are more likely to develop heart disease or have a heart attack than people who aren't depressed.
  • People who have had a heart attack or live with heart failure or another heart or blood vessel condition are more likely to become depressed than people without these diseases.

Evidence is building that when doctors identify and treat depression, it is good for the heart. In September 2008, the American Heart Association (AHA) issued guidelines to raise awareness of the hazardous link between depression and heart disease.

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Depression: Not a "Normal" Response to Heart Disease

People being treated for heart disease — particularly if it is severe — may have difficulty recognizing their own depression. They may accept their sadness as a normal reaction to having an illness that can take the pleasures our of life or, even worse, raise the threat of sudden death. Doctors may easily attribute a patient's reduced activity level, diminished zest for life, or changes in sleep and appetite to "normal" reactions to heart disease.

Many symptoms of heart disease mimic symptoms of depression. Thus, more and more cardiologists and primary care doctors are using formal questionnaires to screen patients for depression. Such tools help doctors find out about eating and sleeping habits, energy level, concentration and the ability to take pleasure from daily activities.

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The Sad Heart

Depression is hard on the heart and the arteries that carry blood to it. Among healthy individuals, depression doubles the risk of sudden cardiac death and increases the chances of having a heart attack or stroke. The risk is even greater in people who already have a heart condition.

What's the connection? Depression is associated with physical changes that can pave the way for heart trouble.

  • Depression has a negative effect on two important hormone systems: the hypothalamic-pituitary-adrenal (HPA) axis and the renin-angiotensin-aldosterone system. They both influence heart and blood vessel health.
  • Scientists have found that signaling molecules called pro-inflammatory cytokines are activated in people with depression. These cytokines appear to promote atherosclerosis and the rupture of cholesterol-filled plaque, which can block blood flow to heart muscle and cause death.
  • Depression can change heart rate and rhythm in unhealthy ways.
  • Depression also activates platelets. (Platelets are small cell fragments in the blood stream that are essential for blood clotting.) Platelets are sometimes described as becoming "stickier" because they are more likely to clump and form clots in the bloodstream.

Behavioral changes brought on by depression may be just as important. A report from the ongoing Heart and Soul Study cited physical inactivity and behavioral factors as major contributors to the connection between depression and heart disease.

People who are depressed find it difficult to:

  • Exercise
  • Pay attention to what they are eating
  • Take medicines needed to protect the heart

They also tend to withdraw from family, friends and other social interactions. This can further boost the risk of heart disease.

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Treating Depression And Heart Disease Together

Medications and psychotherapy and the mainstays for treating depression. They are generally effective for patients with heart disease. But other treatments deserve special mention. One of them is exercise.


Doctors have avoided prescribing a group of antidepressants called tricyclics. Two examples of these medications are imipramine (Tofranil) and nortriptyline (Pamelor). These older medications can affect heart rhythms in harmful ways, weakening an already fragile pump.

Newer antidepressants, including selective serotonin reuptake inhibitors (SSRIs), have been shown to be safe for treating depression in people with heart disease. Small trials suggest they may improve cardiovascular health as well. Other newer antidepressants may also work, but there is less evidence about their risks and benefits for people with depression.

The choice of which SSRI to use depends on patient preference and medical history. The AHA recommends either sertraline (Zoloft) or citalopram (Celexa) as a first choice for heart disease patients who are experiencing a first episode of depression. Carefully designed studies have shown these drugs to be both safe and effective for this group of people. But if it's a repeat episode of depression that was successfully treated with another type of SSRI, then they can restart that particular medicine.


Survivors of a life-threatening heart event may feel more vulnerable or have a new outlook on life. They may feel sad about losing strength or vigor, or anxious about the possibility of sudden death. Psychotherapy may support healthy lifestyle choices and reinforce the commitment to medical and psychiatric treatment. It can also help the person to see these worries more realistically and take more pleasure in life.


A growing body of research shows that a regular exercise program can improve mood in people with mild to moderate depression. It can also be an important add-on for people with severe depression. As a bonus, exercise also helps the heart and blood vessels, lungs, muscles, bones and virtually every other part of the body.

Our understanding of how exercise affects mood is evolving. It has long been understood that exercise promotes the release of endorphins and norepinephrine and improves the supply of oxygen and energy to the brain. Some experts believe that longer-lasting improvements in depression come from the process called neurogenesis.

Neurogenesis refers to the growth of new nerve cells and reinforcement of nerve connections. This process is seen in the hippocampus, one of the areas of the brain that helps regulate mood.

The same changes are seen in people who have responded to other effective treatments for depression.

To reap the brain benefits of exercise, people don't need to wear themselves out. One study, for example, found that moderate-intensity physical activity, such as walking a mile in 15 to 20 minutes, significantly improved symptoms in people with mild to moderate depression, as long as they walked on a regular basis.

The researchers found that people need to be physically active for 35 minutes a day, five times a week or for 60 minutes a day, three times a week to reap the benefits. Mood benefits were not apparent, however, in people who were moderately active for only 15 minutes a day, five days a week.

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Encouraging Treatment for Depression

Experienced mental health professionals know that the biggest barrier to treating depression may be a person's inability to admit they have a problem or their reluctance to get help. To overcome these barriers, patients with heart disease need to know that untreated depression puts them at increased risk for additional heart problems.

Cardiologists and primary care physicians can promote better outcomes by routinely asking their patients about symptoms of depression and encouraging them to address mood problems directly. For people who are embarrassed by the idea of mental health treatment, the most persuasive argument may be that treating depression can make the heart healthier and lead to a longer, more worthwhile life.

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Michael Craig Miller, M.D. is editor-in-chief of the Harvard Mental Health Letter and an assistant professor of psychiatry at Harvard Medical School. Dr. Miller has an active clinical practice and has been on staff at Beth Israel Deaconess Medical Center for more than 25 years.

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