Targeting Sympathetic Overactivity in Heart Failure Patients With Statins
Status:
Completed
Trial end date:
2014-07-01
Target enrollment:
Participant gender:
Summary
Heart failure (HF) is a leading cause of morbidity and mortality in the United States with
the incidence and prevalence of the disease on a continual rise. An overactive sympathetic
nervous system has become a hallmark characteristic of HF. Although sympathetic activation is
initially beneficial to maintain cardiac output, blood pressure and perfusion to vital
organs, over the long term it becomes deleterious contributing to the worsening of HF and
sudden cardiac death. Indeed, recent findings in HF patients suggest that the sympathetic
overactivity is not just a marker of poor prognosis but it plays a causative role in the
development of the disease. Thus, the sympathetic nervous system constitutes a putative drug
target in the treatment of HF. However, despite aggressive medical management, including
conventional anti-adrenergic strategies, sympathetic nerve activity (SNA) has been shown to
remain abnormally high in HF patients and improvements in survival have been limited. Thus,
other treatment strategies that include reducing SNA and its deleterious consequences are
warranted. Recent findings from clinical trials indicate that 3-hydroxy-3-methyl-glutaryl
coenzyme A reductase inhibitors (statins) improve survival irrespective of cholesterol
lowering bringing the pleiotropic (i.e., cholesterol independent) effects of statins to the
forefront. An important pleiotropic effect recently reported in experimental HF, that has yet
to be directly tested in human HF, is the ability of statins to reduce resting sympathetic
outflow. Several studies in pacing-induced HF rabbits have demonstrated that statins
normalize the excessive sympathetic activation in the HF state. Thus, the goal of this
project is to determine whether these findings in experimental HF can be translated to the
clinical setting of human HF. Our central hypothesis is that statins reduce sympathetic
overactivity in HF patients. To test this hypothesis we will directly measure muscle SNA and
perform a randomized crossover placebo control study. Subjects will come to the research
laboratory before and after the administration of Simvastatin at a standard therapeutic
dosage of 40 mg. per day or placebo for 1 month