Targeting Sympathetic Overactivity in Heart Failure Patients With Statins

• Status: Completed
• Trial end date: 2014-07-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: N/A
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Missouri-Columbia
• Collaborator: University of Nebraska
• Treatments: Simvastatin

Criteria

Inclusion Criteria:

• Male and females of all ethnic backgrounds ranging aged 18 to 70

• Ages 18-70 yrs

• Patients with congestive heart failure diagnosed on clinical history, a routine exercise test, echocardiography and/or routine cardiac catheterization, in functional class I-III

• Patients with heart failure due to ischemic and non-ischemic etiologies

• Normotensive and not taking blood pressure controlling medications

Exclusion Criteria:

• Low blood pressure (<100/60)

• End stage renal disease

• Chronic Obstructive Pulmonary Disease (COPD) with concurrent daily use of inhalers

• Peripheral neuropathy

• Pregnant women