Medicine pursues a mind-heart connection

The melancholy mind and the broken heart: For poets and philosophers through the ages, the two have been fellow travelers, chicken and egg, bookends in a long litany of tragedies.

Leave it to medical researchers, then, to put the dark bond between heart and mind under a microscope — and find even deeper mysteries.

Nearly 25 years of research has drawn a clear connecting line between depression and heart disease, making the link Exhibit A in the modern compendium of mind-body connections.

But that research has yet to explain the connection. And it has yet to convince many cardiologists that depression care could be a tool in preventing and treating heart disease.

"That you can die of a broken heart isn't a new idea. But unfortunately, the idea is much more complex than any of us expected," says Dr. Alexander Glassman, a psychiatrist with the New York Psychiatric Institute.

Complex, yes. But the bond between heart disease and depression is also undeniable.

People who have had episodes of depression are roughly twice as likely as those with no such history to develop cardiovascular disease in their lifetimes — making depression a more powerful predictor of heart disease than high blood pressure, elevated cholesterol readings, a history of smoking or diabetes.

After a heart attack, surgery to clear blocked arteries or a diagnosis of heart failure, a person is three to four times more likely than a healthy peer to show signs of clinical depression. Those who show depressive symptoms in the weeks and months following a heart attack or an artery-clearing procedure are two to three times more likely than those who don't to die or have another cardiovascular "event" within a year. The more severe a patient's depression, the worse the prognosis.

The link is not lost on many seasoned cardiologists. Dr. Marc Penn of the Cleveland Clinic's Bakken Heart-Brain Institute says it's hard not to be pessimistic when he sees a patient with clear signs of depression. In such cases, it's a cardiologist's ethical obligation to ensure that a patient gets treated for depression, he adds — even though there's no proof that such treatment will improve the outcome of his heart disease.

That lack of proof is only one of the puzzles. Many central questions remain: Which affliction comes first, and does one cause the other? Or do the two spring from some common source?

Could early depression treatment head off development of heart disease in the first place — or could better management of cardiac risks prevent depression?

And why, when the connection between the two seems so clear, would anyone tend to the heart and not the mind?

For busy cardiologists, these uncertainties pose a dilemma. In 2008, the American Heart Assn. called for routine depression screening of heart patients. Three years on, many remain wary of the value of doing so.

"When the rubber hits the road in cardiology clinics, routine screening [for depression] is hard," says Dr. Jeffery Huffman, a Harvard University psychiatrist and researcher who consults with heart patients admitted to Massachusetts General Hospital. The questions eat up time, he says — and then, if a patient says he or she is depressed, what next? Few heart specialists have developed close working relationships with mental health professionals, Huffman says, and patients — already overwhelmed with their heart troubles — are often resistant to going.

The hurdles are both medical and cultural.

Treating an ailing heart is no medical walk in the park, but treating depression is a thicket of murk and uncertainty by comparison. The well-charted sinews, electrical currents and hydraulic dynamics of the heart lend themselves to clean diagnoses, straightforward treatments and clear measures of whether treatment has worked.

Depression, by contrast, is shrouded in social stigma, difficult to assess, tricky and time-consuming to treat, and in as many as half of patients, remarkably stubborn. It's an awkward subject for physicians more comfortable explaining QT intervals and ejection fractions than inquiring about feelings of worthlessness or guilt.

Physicians "are frequently timid about assessing emotional problems," wrote UC San Diego psychiatrist Joel E. Dimsdale in the American Journal of Cardiology in June, while commenting on two finding that early anxiety is strongly linked to later heart problems. "It is odd that we thread catheters, ablate lesions, and give rectal exams but are uncomfortable asking patients about their lives."

The fact that there is scant evidence that treating the depression will help the patient's heart only adds to doctors' reluctance to probe their patients' psyches. The American Heart Assn.'s 2008 advisory concluded that patients with heart disease should routinely be screened for depressive symptoms, that a relatively new generation of antidepressants, the selective serotonin reuptake inhibitors (SSRIs), are safe for use in this patient population, and that antidepressant use can increase a patient's willingness to make recommended lifestyle changes and to stay on medications aimed at reducing the odds of further damage to the heart.

But that was as far as the statement could go, says Glassman, who coauthored the guidelines. Trials in which depressed heart patients got treatment — medication, psychotherapy, exercise regimes or stress-reduction techniques — have improved patients' cardiac outcomes anywhere between modestly to not at all.

Only one study, published in 2005, has found more than modest evidence that treating depression might improve a heart patient's prognosis. Among depressed heart attack patients who took SSRI antidepressants following their hospitalization, the likelihood of dying or having another heart attack dropped 43% over a 21/2 -year period compared to those who had not been treated with SSRIs. But that study allowed patients and their physicians to choose whether they got the drugs — a shortcoming that limits the strength of the finding, Glassman says. (Several trials are now underway to explore whether depression treatments, when they're successful, can improve heart patients' prognoses.)

Increasingly too, researchers are looking for deeper physiological connections. As they do so, they're finding that the early harbingers of heart disease — measures such as inflammation, platelet aggregation in the blood and endothelial function — also play a role in depression, suggesting the two may have a common root.

These studies focus on a measure of overall wellness called "good autonomic tone" — a state in which a patient's stress hormones are properly regulated, his heartbeat shows small variations and his blood vessels expand and contract properly in response to changes in blood flow. Increasingly, researchers are recognizing that when autonomic tone is out of whack, inflammation increases. Heart function suffers. And so does mood.

"The physiology is becoming better understood," says Penn. "We're starting to put the whole package together and really understand" some of the heart-depression links. As this research proceeds, he says, physicians may learn better ways to head off heart disease and depression before they take hold — or to limit the collateral damage once one of the two has planted its flag.

Other researchers view the connection more simply: that the sadness, low energy, poor sleep, anxiety and guilt that come with depression make us less likely to get out and exercise, more likely to engage in unhealthy behaviors such as smoking and drug and alcohol abuse, and more resistant to staying on medications prescribed by doctors.

The result: Depressive behavior makes heart disease more likely; and once heart disease sets in, depression continues to cast a long shadow, making a patient less hopeful and engaged in her recovery, and thus, more likely to succumb.

That finding emerged strongly from a three-year study called "Heart and Soul," published in 2008. Its lead author said she was completely surprised by the findings — that depressive behaviors, including poor diet, lack of exercise, fitful compliance with medication schedules and doctor appointments, trumped a raft of physiologic measures in predicting a patient's subsequent heart disease.

"I was absolutely floored at how strong an effect the health behaviors had, and how relatively little effect these biological factors had," said Dr. Mary Whooley, a UC San Francisco epidemiologist.

The message from "Heart and Soul," says Whooley, is both simple and humbling. Patients should get treatment for their depression because it saps them of the energy and will they need to keep their hearts healthy or help them heal, says Whooley. And physicians should brace for frequent failure in their efforts to save patients from their unhealthy habits.

"As physicians, we're always saying to patients, 'You should lose weight and exercise,' but it really doesn't go very far," Whooley says. "It's so difficult to change behaviors."

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