Probing the factors behind heart attacks

Behavioral researchers have teamed up with cardiologists to study how stress affects the heart.

By Beth Azar
Monitor staff

A short, heavyset man sits in a low-backed swivel desk chair. He?s not wearing a shirt, and his chest is covered with 21 electrode patches hooked up to a $40,000 cardiac readout machine. Six researchers hover around him?a cardiac nurse, three psychologists, a cardiologist and a lab technician. He smiles slightly, intrigued.

Then John Quigley, a tall, intimidating man, barges into the room and brusquely announces that he will administer a mathematics test to the man in the chair. He plays a tape that barks out the instructions: The man?s job is to count backwards by sevens as quickly and accurately as he can from a designated four-digit number.

The first number is 1,039 and the man struggles to accomplish the task. 'Faster!' yells Quigley as the man squeaks out numbers. 'You?re slowing down.' The man?s heart rate begins to climb. He continues, noticeably flustered. 'Wrong!' yells Quigley. 'Speak loudly and look at me. Accuracy and speed!'

This continues for four minutes as the man in the chair grows increasingly agitated and angry.

That?s what graduate student Quigley and the other researchers want. As part of a series of studies approved and funded by the National Heart Lung and Blood Institute, they?re testing the effect of mental stress on heart function. The man being tested has heart disease. He?s been briefed on the study?s minor risks to his health, and the researchers and medical staff carefully monitor his physical condition throughout the experiment.

The work is part of an interdisciplinary field called behavioral cardiology. Over the past decade or so, such research has documented that mental stress is as potent a trigger of acute heart dysfunction in people with coronary-artery disease as is strenuous exercise. Furthermore, treating mental stress may be as beneficial for patients as increasing their stamina for exercise.

'We?re not studying how long-term stress affects the development of heart disease,' say psychologist David Krantz, PhD, of the Uniformed Services University of the Health Sciences (USUHS), who directs the study Quigley is working on. 'We?re interested in what triggers heart attacks or sudden death in people who have heart disease.'

In particular, they?re looking for the mechanisms by which stress acts on the cardiovascular system to trigger acute symptoms of heart disease, such as angina, heart attack or sudden death. It?s a task that would be nearly impossible without collaboration between psychologists and medical researchers, says Krantz.

The interdisciplinary collaboration enhances the strength of the studies, agrees Georgetown University Medical School cardiologist John Gottdiener, MD, who works with Krantz. Psychology brings a rigor to the study design and statistical analyses that medical researchers haven?t traditionally had in clinical research. On the flip side, cardiologists provide highly sophisticated and precise measures of cardiac function and an understanding of heart physiology that psychologists lack.

Sensitive measures

The patient described above is the 10th enrolled in what will be a large study of men and women at risk for sudden death. They are cardiology patients who, because of earlier heart trouble, have internal cardiac defibrillators (ICDs) inserted in their chests. The ICDs regulate the heart if their heart rates get too high or if the patient goes into arrhythmia. The researchers hope to identify mental-stress-related markers that predict whether a patient?s ICD will discharge during daily living.

They?re not trying to induce a discharge in the lab; they?re just stressing patients enough to cause ischemia?a condition that occurs often in patients with coronary-artery disease when the heart isn?t getting enough blood. Ischemia is usually painless and benign so it can be induced ethically in the lab with study participants well aware of the risks, says Krantz. And it?s interesting to behavioral cardiology researchers because people who are ischemic are known to be at increased risk for later heart problems.

The researchers are testing patients during exercise and mental stress, both of which have been found to cause ischemia. Although exercise is known to protect people from heart problems, it can be dangerous in people with heart disease, many of whom aren?t accustomed to exercise, says psychologist James Blumenthal, PhD, of Duke University. Heart patients need to build up their stamina slowly, and as they do, their risk of ischemia decreases.

A standard electrocardiogram easily picks up exercise-induced ischemia, but may miss mental stress-related ischemia, research finds. For that, researchers need to use more sensitive measures.

For example, when 'patient 10' began to get agitated by Quigley?s badgering, a technician injected him with a dose of a radioactive marker used for nuclear imaging. Cardiologists use nuclear imaging to create a moving picture of the patient?s beating heart. Areas that don?t move are experiencing ischemia, explains Veterans Affairs Hospital cardiologist Dan Fernicola, MD, who works with Krantz? team.

Another technique sometimes used with volunteers is coronary angiography, which allows researchers to measure blockage in coronary arteries. They disperse dye into the arteries through a tube and then use a type of x-ray to view the arteries.

Angiography has allowed researchers to examine physiological differences between mental stress-related ischemia and exercise-related ischemia. Lab tests show that ischemia triggered by mental stress occurs at lower heart rates than ischemia triggered by exercise. That is, it?s triggered when the heart is demanding less blood, says Krantz. That means that during mental stress?say a fight with one?s spouse?blood flow to the heart becomes inadequate sooner than it does during exercise.

When Krantz and his colleagues used angiography to look closer at what?s happening, they find that mental stress causes constriction in the coronary arteries at points where there is coronary-artery disease. Mental stress not only demands more blood but simultaneously decreases blood flow to parts of the heart, says Krantz. This could be what causes ischemia at lower heart rates.

These studies would have been impossible several years ago, before such precise measurement techniques were available, says psychologist Willem Kop, PhD, who works with Krantz. And psychologists certainly couldn?t take or interpret the measurements without the help of their cardiology partners, says Gayle Baker, Krantz? research assistant.

As for the behavioral side of the studies, most cardiologists wouldn?t know where to begin, admits Gottdiener. Most behavioral cardiology teams use a battery of techniques to induce mental stress in patients. Krantz? team, for example, uses two methods: the mental arithmetic challenge described above, and an anger- recall task that requires patients to describe out loud a personal event that made them angry.

Some patients respond better to one or the other, says Quigley. Indeed, patient 10 barely responded when he recalled a recent fight he had with his wife. But he became exceedingly agitated during the mental arithmetic test. Quigley and the other psychologists always debrief the patients after the tasks, explaining that they were trying to induce anger and allowing them time to calm down. Indeed, by the time patient 10 was done, he was smiling and joking.

Promising findings

Research on stress and acute cardiac function has been so successful, some aspects of what researchers have found are beginning to be applied in a clinical setting, says Krantz.

Several teams find that patients who show signs of mental-stress- induced ischemia?about 50 percent of cardiac patients?are at increased risk for future problems, including heart attacks and angina that could lead to bypass surgery or death. The work also indicates that mental stress in daily life can trigger these problems as effectively as strenuous exercise.

And since people with coronary-artery disease infrequently exercise, mental stress may be a more potent trigger of cardiac events, says Krantz.

An intervention study directed by Blumenthal has preliminary evidence that a mental stress?reduction program is more effective in preventing cardiac relapse in patients than an intervention that builds up patients? physical fitness. The stress-reduction intervention significantly reduced their risk of heart attack and other adverse cardiac events for up to five years. The exercise intervention program provided a much smaller and statistically nonsignificant effect, says Blumenthal, whose study was published in Archives of Internal Medicine (Vol. 157, p. 2213?2223).

It will take a strong collaboration between behavioral researchers and medical researchers to discover the mechanisms by which mental stress triggers heart dysfunction, says Blumenthal. He relies on his medical colleagues to hypothesize on physiological mechanisms that might underlie how behavior can translate into outcome.