The effect of statins on sympathetic activity: a meta-analysis

Abstract

ObjectiveBeyond lipid-lowering properties, statins decrease sympathetic nervous activity. Due to the limited number of studies and included participants, a meta-analysis of randomized, placebo-controlled studies using microneurography (MSNA) was performed to assess sympatholytic effect of statins.MethodsWe conducted a comprehensive search of online databases (Cochrane, Embase, and EBSCO) for published human studies up to April 2014. Randomized controlled trials (parallel and crossover design) were eligible for inclusion if results of statins versus placebo treatments on sympathetic activity were measured with MSNA.ResultsData from five studies with a total number of subjects n = 82 were included into the meta-analysis. MSNA expressed as bursts/min and as bursts/100 heartbeats was lower in the statin group than in the placebo group with a mean difference of −4.37 95 % CI (−7.03; −1.70), p < 0.0013 and −5.85 95 % CI (−7.56; −4.13), p < 0.0001, respectively. No significant publication bias was observed. Meta-regression revealed no significant effect of baseline total cholesterol or dose of statin. No change in blood pressure and heart rate was observed.ConclusionsPublished data show that regardless of type and dose, statins reduce sympathetic activity measured by microneurography. The role of decreased sympathetic outflow during statin therapy on clinical end points needs to be clarified.

Effects of Statin Treatment on Inflammation and Cardiac Function in Heart Failure: An Adjusted Indirect Comparison Meta‐Analysis of Randomized Trials

“…An interesting finding of the current analysis was that the magnitude of effects of statins on improvement of LVEF was dependent on the etiology of HF; specifically, trials with a considerable number of patients with nonischemic HF had larger improvements in LVEF than did patients with ischemic etiology. The reasons for the different hemodynamic responses in ischemic and nonischemic etiologies have not been clarified but may be related to differences between the two statin types in the degree of activation of the beta‐adrenergic pathway which are unrelated to cholesterol‐lowering effects . Regardless of the factors involved, the superior treatment effect of lipophilic statins on LVEF was apparent in both ischemic and nonischemic HF compared with hydrophilic statins.…”

Statin Short-term Inhibition of Insulin Sensitivity and Secretion During Acute Phase of ST-Elevation Myocardial Infarction

“…In the very early phase of MI, IS declines because of a spectrum of mechanisms that include the neurohumoral activation and acute phase of inflammatory response 3,24,25 . Although statins can quickly reduce inflammatory activity 26 and sympathetic activation 27 , its above-commented ability to inhibit prenylation seems to predominate in the modulation of IS during acute stress according to our EHC data 28 . Indeed, in in vitro model with 3T3-L1 adipocytes, statins promote downregulation of insulin-sensitive GLUT-4 and up-regulation of GLUT-1; these effects are reversed by mevalonate, demonstrating that inhibition of isoprenoid biosynthesis causes insulin resistance in adipocytes 29 .…”

Central Angiotensin-II Increases Blood Pressure and Sympathetic Outflow via Rho Kinase Activation in Conscious Rabbits

“…Indeed, therapeutic doses of statins decrease Rho kinase activity in patients with atherosclerosis in an LDL-independent manner 63 . Our lab has similarly found that statin treatment improves autonomic function in experimental and clinical heart failure independent of LDL-lowering effects 64–68 , and clinical studies in patients with hypertension and chronic kidney disease support the sympatholytic effect of statins in humans regardless of the presence of hyperlipidemia 69–72 . Given the strong associative 73–75 and experimental 76,77 data linking autonomic function and mortality in cardiovascular disease, the sympatholytic effects of statins through Rho kinase inhibition may be an important mechanism by which these drugs reduce cardiovascular risk.…”