Fight or Flight: In weighing cardiac risk factors, doctors are overlooking autonomic tone

KANSAS CITY, MO. —  If you think you know which of your patients is most likely to suffer a heart attack, think again. Although some factors, such as hypertension, obesity, and high cholesterol, are obvious predictors of a heart attack, physicians are not getting the complete picture unless they also know how their patients are faring in four key parameters of autonomic function, says James O’Keefe Jr., MD, a cardiologist with Mid-America Heart Institute here. The parameters are:

• Elevated resting heart rate of greater than 90 beats per minute. “The best prognostic marker on an acute infarct EKG is resting heart rate, not Q waves or ST-segment variation,” says Dr. O’Keefe.
• Intolerance to routine exercise. Of healthy middle-aged adults, 11% to 26% fail to achieve 85% of the age-predicted maximum heart rate during a stress test. “This increases risk of dying from a CV event even if angiography and perfusion images are normal,” he says.
• Heart rate recovery after exercise. Twenty percent of apparently healthy adults have heart rates that do not decrease by at least 13 beats per minute during the first minute after peak exercise. “They have a four times greater chance of dying from a CV event within the next five years,” says Dr. O’Keefe.
• Low heart-rate variability. It’s measured by observing change in heart rate for one minute during deep breathing. Failure to change heart rate by at least 10 beats per minute increases risk for MIs, coronary atherosclerosis, and sudden cardiac death, according to Dr. O’Keefe.

These four measures of autonomic tone are powerful predictors for CV events, stresses Dr. O’Keefe, whose review of autonomic dysfunction appeared in Mayo Proceedings. But abnormal autonomic tone is the most sensitive predictor for cardiac and arrhythmic death, even more so than ventricular tachycardia. “Common medications and emotional stress chronically and inappropriately activate the sympathetic nervous system, which increases risk for cardiovascular events,” he says. “Autonomic dysfunction with excessive sympathetic tone affects perhaps 25% of American adults. It’s a major missing piece of the puzzle in predicting cardiovascular risk. It’s not controversial, but it’s widely ignored by physicians.”

Heart-rate recovery after exercise is perhaps the most important predictor, yet most physicians ignore it, according to Carl Lavie, MD, a noninvasive cardiologist and codirector of Cardiac Rehabilitation and Preventive Cardiology at the Ochsner Heart and Vascular Institute in New Orleans. “Most of the time heart-rate recovery is not even included in the treadmill report,” he says. “Even when it is, physicians don’t analyze these data. We need to realize there are specific ways to assess autonomic function that have prognostic capability. We can start by using all the treadmill data.” Psychosocial factors such as depression, sleep deprivation, anxiety, social isolation, and hostility stimulate sympathetic tone or suppress parasympathetic tone and are potent independent predictors for future risk of MI, sudden cardiac death and strokes. Depression, for example, elevates resting heart rate, decreases heart rate variability, suppresses parasympathetic tone and elevates plasma norepinephrine. “A history of major depression is among the strongest cardiovascular risk factors,” says Dr. O’Keefe. Similarly, lack of social connections disturbs normal autonomic tone and is known to increase risk for CV events in healthy populations as well as those with known cardiovascular disease. “Intuitively we’ve known all of this for years,” Dr. O’Keefe notes. “But now we have the science to back up our intuition. Stress does matter. We understand the mechanism of action. The science of the mind-heart connection is a science that’s maturing.” Exercise, stress reduction, and social connections improve autonomic function by activating the parasympathetic nervous system. Regular exercise lowers resting heart rate, improves heart rate recovery and heart rate variability. It also reduces risk of sudden cardiac death. It suppresses sympathetic activity through many indirect mechanisms including weight loss, reduced anxiety and depression, and improved insulin sensitivity.

Cardiac rehabilitation and exercise significantly improved autonomic tone in 40 heart patients studied by Dr. Lavie, and other studies he has done show mortality reductions of 20% to 25%. “No other factors improved enough to explain why mortality fell so much,” he says. In addition, exercise was associated with a 50% improvement in his patients’ depression and hostility scores. Dr. Lavie estimates that half to two-thirds of his practice relates to autonomic dysfunction. “Excessive sympathetic nervous system stimulation is an important final pathway by which conventional risk factors like smoking, stress, obesity, diabetes and high blood pressure take their toll,” he says. For example, elevated fasting insulin levels increase sympathetic activity, heart rate and heart rate variability. Chronic sympathetic activation also plays a role in the 20% to 50% of CV events that aren’t explained by conventional causes, according to Dr. Lavie. These include middle-aged adults with no risk factors who have heart attacks and CV events related to high homocysteine levels or chronic infections. “If physicians want to prevent cardiovascular disease,” says Dr. Lavie, “they need to keep the importance of autonomic tone in their minds.”  —  Howard Bell

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