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Short-Term Use Of Statin Drugs Reduces Damaging Sympathetic Nervous System Overactivity In Heart Failure Patients

Statin drugs, known primarily for their ability to lower cholesterol, also may reduce the overactive sympathetic nervous system response that contributes to the worsening of heart failure and increases the risk of sudden cardiac death. A result of heart attack or conditions such as coronary artery disease or hypertension, heart failure is the leading cause of morbidity and mortality in the United States.

On May 1, Dr. James Fisher, a postdoctoral fellow in the University of Missouri laboratory of Dr. Paul Fadel, reported one of the first studies on the effect of the popular statin drugs on the sympathetic nervous system activity of human patients with heart failure. His presentation at Experimental Biology 2007 in Washington, DC, is part of the scientific program of The American Physiological Society.

Heart failure, sometimes called congestive heart failure, is a chronic condition in which the heart can no longer pump enough blood to the rest of the body, causing damage and negatively impacting the quality and duration of life.

In several large clinical trials, cholesterol-lowering statin medications improved survival and other health outcomes in patients with heart failure, an effect that appeared not to be solely due to lowering these patients’ cholesterols levels. In the search for a possible mechanism to explain this observation, scientists have turned to measures of sympathetic nervous system activity. 

The sympathetic nervous system is a primary determinant of control of blood pressure and heart rate. When a heart begins to fail, the sympathetic nervous system works harder to compensate by helping to maintain heart function, blood pressure and the delivery of needed blood to vital organs and peripheral muscles. While this increased activity is beneficial in the early stages of heart failure, prolonged full-tilt sympathetic nervous system overactivity soon becomes harmful, causing damage to heart and kidney, raising the risk of lethal arrhythmias and changing the peripheral vasculature in deleterious ways.  In fact, several studies have found that heart failure patients with high sympathetic nerve outflow have a greatly increased risk of mortality compared to patients with lower sympathetic outflow.  

The largest and clearest differences in sympathetic nervous system activity between individuals with and without heart failure can be seen in sympathetic nervous system activity while resting, when the body is placing no unusual demands on the heart.  The University of Missouri researchers took particular note of an earlier animal study.  When scientists at the University of Nebraska earlier had induced in rabbits heart failure similar to that experienced by humans, increases in the animals’ resting sympathetic nervous system activity or flow quickly paralleled the overactivity that is a hallmark characteristic of human heart failure.  Remarkably, treatment with statin drugs lowered the animals’ resting sympathetic nervous system activity to normal. -more-

But would statins do the same thing in humans with heart failure? Dr. Fisher and Dr. Fadel now have worked with five patients: four men and one woman, between the ages of 49 and 61 (average age 53), with longstanding mild-to-moderate heart failure, undergoing treatment at the University of Missouri. Their sympathetic nervous system activity was measured with a recording electrode placed in the peroneal nerve of the lower leg, which provides a global measure of the sympathetic nervous system activity that is controlling blood flow to skeletal muscle. This unique approach gives the researchers a less ambiguous, more robust measure of the effect of treatment on the sympathetic nervous system outflow because it directly measures the firing of sympathetic nerves.  Although plasma norepinephrine, the transmitter released when sympathetic nerves fire, can be measured in the blood, this marker is affected by factors such as clearance and reuptake, making it a less precise marker.

The patients continued their regular treatment for heart failure, but now also began to take 40 mg per day of Simvastatin (Zocar). After one month of treatment, all patients had reduced sympathetic nerve activity while resting. Although none of the patients had experienced cholesterol or blood pressure levels elevated enough to require treatment, significant decreases in cholesterol and diastolic blood pressure also were absorbed and considered beneficial for the patients’ overall health. 

The bottom line, says Dr. Fadel, is that even short term treatment with a low level of statin medication was sufficient to significantly lower resting sympathetic nerve activity in all five patients, thus lowering a factor known to be associated with increased mortality in heart failure patients. He believes these preliminary results are “promising and quite exciting.”

The researchers now are expanding the number of patients in the ongoing study and including more study measurements and procedures in order to begin to understand the mechanisms of how statins may be influencing the sympathetic nervous system.

This research was supported in part by the University of Missouri. Patients were seen in Dr. Fadel’s laboratory at the Harry S. Truman Veterans Affairs Hospital in Columbia, Missouri.

Physiology is the study of how molecules, cells, tissues and organs function in health and disease. Established in 1887, the American Physiological Society (APS) was the first U.S. society in the biomedical sciences field. The Society represents more than 10,500 members and publishes 15 peer-reviewed journals with a worldwide readership.