APS Presentation 3:30 p.m. EDT, Tuesday, May 1
Pressroom presentation 9 a.m. EDT, Tuesday, May 1
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Sarah Goodwin
(202) 249-4165 April
28-May 2
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.
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