Middle-aged women with no obvious signs of cardiac trouble may be prone to depression and the eventual development of heart disease if their heart rate varies less than expected in response to fluctuations in the body’s hormone levels, according to findings from a substudy of the Women’s Health Initiative published today in the Archives of Internal Medicine.

The study results are the first to note an association between lower heart rate variability — a measure of how the heart responds to changing levels of hormones produced by the sympathetic nervous system — and symptoms of depression in a large population of otherwise healthy postmenopausal women. They also support the notion that increased hormone levels not only affect mood but also can lead to heart disease by promoting higher blood pressure, heart rhythm problems and blood platelet stickiness, which in turn can cause blood clots to lodge in arteries and trigger a heart attack.

“These are patients without obvious heart disease,” said Dr David S Sheps, associate chief of cardiovascular medicine at UF’s College of Medicine and the Malcom Randall Veterans Affairs Medical Center. “We’re finding the same kinds of things that are found in cardiac patients with depression are also found in the normal population. This supports the hypothesis that depression is related to or may actually be associated with increases in abnormalities in the autonomic nervous system, the main regulator of heart rate, which may actually put people who have no obvious disease more at risk for developing disease in the future.”

UF researchers joined with investigators at nine other medical centers to evaluate 2,699 postmenopausal women between the ages of 50 and 83 years who were enrolled in the Myocardial Ischemia and Migraine Study, an ancillary study to the Women’s Health Initiative. Participants wore a small electrocardiographic monitoring device that measured heart rate and rhythm as they went about their daily activities. They also completed standardized questionnaires that screen for signs of depression.

About one in 10 of the study participants had depressive symptoms. Those women tended to have lower heart rate variability and a higher average heart rate.

Past studies conducted elsewhere have linked decreased heart rate variability with increased death from cardiac complications, both in healthy patients and those with heart disease. Recent research also has shown decreased heart rate variability accelerates the development of atherosclerosis and increases the likelihood of dying after a heart attack. In addition, it is associated with heart rhythm abnormalities and sudden death.

“Decreased heart rate variability may not only contribute to increased cardiac morbidity and mortality in (coronary artery disease) patients, but also may be the link that places depressed subjects with no known history of CAD at risk for cardiovascular disease,” the authors wrote in the journal. The paper’s lead author was Dr Chin K. Kim, a postdoctoral fellow at UF’s College of Medicine who collaborated with researchers from the Albert Einstein College of Medicine at Yeshiva University, the University of Alabama at Birmingham, George Washington Medical Center, the University of California, and others.

The relationship between depression and heart disease has garnered much interest among medical professionals in recent months. Sheps is editor of the journal Psychosomatic Medicine, which published a supplement devoted to depression and heart disease May 23. Depression raises the chance of suffering a heart attack or dying two to three times above normal, making it a risk factor on par with smoking or having high blood pressure.

Depression is twice as common in women as in men. Women who have an underlying cardiac condition also frequently develop symptoms that differ from those commonly found in men with the same problem, making it easy for some practitioners to overlook a diagnosis of heart disease, Sheps said.

“For example, women are much more likely to present with chest pain which is not typical for angina. Typical angina is chest pain that occurs with exertion and that is relieved by rest,” he said. “Women may not present with that or they may present with other types of atypical symptoms more frequently than men do. That can sometimes be difficult for the physician to interpret or throw them off the diagnosis of heart disease.”

Dr Robert N. Golden, professor and chairman of psychiatry at the University of North Carolina at Chapel Hill, said the study findings are important because of the higher prevalence of clinical depression among women.

“We have known for some time that depression is a potentially deadly disease, not only because of the associated risk for suicide, but also because of increased mortality from other medical conditions,” Golden said. “This research report helps explain one potential mechanism for increased mortality, namely the abnormal heart rate variability in older women with depression.”

UF researchers said they will continue to track the study participants in a search for other markers of heart disease-related complications, and to see whether heart rate variability could be used to assess long-term outcome in these patients.

“We will be able to see whether, for example, these changes predict development of adverse events in the future,” Sheps said.

Researchers don’t yet fully understand the connection between depression and heart disease, but Golden said chemical communication systems could be the culprit. Levels of the hormone norepinephrine often are altered in depression and are known to affect blood pressure and heart function, he said, and other chemicals, such as serotonin, are involved in depression and can affect the formation of blood vessel disease in the heart and throughout the body.

“These findings reinforce the importance and urgency of long-term depression treatment studies which examine medical as well as psychiatric aspects,” Golden added. “Can we prevent the development of heart disease through more vigorous efforts to identify and thoroughly treat depression early in its course? This might not only improve the quality of life, but also prevent the potentially deadly consequences of depression-associated ‘silent’ heart disease.”