The pleiotropic effects of statins – From coronary artery disease and stroke to atrial fibrillation and ventricular tachyarrhythmia

Adam Oesterle, James K. Liao

Research output: Contribution to journalReview article

11 Citations (Scopus)

Abstract

Statins, 3-hydroxy-methylglutaryl coenzyme A reductase inhibitors, have been used for decades for the prevention of coronary artery disease and stroke. They act primarily by lowering serum cholesterol through the inhibition of cholesterol synthesis in the liver, which results in the upregulation of low-density lipoprotein receptors in the liver. This results in the removal of low-density lipoprotein-cholesterol. Studies have suggested that statins may demonstrate additional effects that are independent of their effects on low-density lipoprotein-cholesterol. These have been termed “pleiotropic” effects. Pleiotropic effects may be due to the inhibition of isoprenoid intermediates by statins. Isoprenoid inhibition has effects on the small guanosine triphosphate binding proteins Rac and Rho which in turn effects nicotinamide adenine dinucleotide phosphate oxidases. Therefore, there are changes in endothelial nitric oxide synthase expression, atherosclerotic plaque stability, pro-inflammatory cytokines and reactive oxygen species production, platelet reactivity, and cardiac fibrosis and hypetrophy development. Recently, statins have been compared to the ezetimibe and the recently published outcomes data on the proprotein convertase subtilisin kexin type 9 inhibitors has allowed for a reexamination of statin pleiotropy. As a result of these diverse effects, it has been suggested that statins also have anti-arrhythmic effects. This review focuses on the mechanisms of statin pleiotropy and discusses evidence from the statin clinical trials as well as examining the possible anti-arrhythmic effects atrial fibrillation and ventricular tachyarrhythmias.

Original languageEnglish (US)
Pages (from-to)222-232
Number of pages11
JournalCurrent Vascular Pharmacology
Volume17
Issue number3
DOIs
StatePublished - Jan 1 2019
Externally publishedYes

Fingerprint

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Tachycardia
Atrial Fibrillation
Coronary Artery Disease
Stroke
Anti-Arrhythmia Agents
Terpenes
LDL Cholesterol
Oxidoreductases
Cholesterol
LDL Receptors
Nitric Oxide Synthase Type III
Liver
Atherosclerotic Plaques
Coenzyme A
Guanosine Triphosphate
NADP
Reactive Oxygen Species
Carrier Proteins
Fibrosis

Keywords

  • Atrial fibrillation
  • Cholesterol
  • Coronary artery disease
  • Low density lipoprotein
  • Pleiotropy
  • Statins
  • Stroke

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

The pleiotropic effects of statins – From coronary artery disease and stroke to atrial fibrillation and ventricular tachyarrhythmia. / Oesterle, Adam; Liao, James K.

In: Current Vascular Pharmacology, Vol. 17, No. 3, 01.01.2019, p. 222-232.

Research output: Contribution to journalReview article

@article{fe03d595c079471aa2bdfc3a241b76a9,
title = "The pleiotropic effects of statins – From coronary artery disease and stroke to atrial fibrillation and ventricular tachyarrhythmia",
abstract = "Statins, 3-hydroxy-methylglutaryl coenzyme A reductase inhibitors, have been used for decades for the prevention of coronary artery disease and stroke. They act primarily by lowering serum cholesterol through the inhibition of cholesterol synthesis in the liver, which results in the upregulation of low-density lipoprotein receptors in the liver. This results in the removal of low-density lipoprotein-cholesterol. Studies have suggested that statins may demonstrate additional effects that are independent of their effects on low-density lipoprotein-cholesterol. These have been termed “pleiotropic” effects. Pleiotropic effects may be due to the inhibition of isoprenoid intermediates by statins. Isoprenoid inhibition has effects on the small guanosine triphosphate binding proteins Rac and Rho which in turn effects nicotinamide adenine dinucleotide phosphate oxidases. Therefore, there are changes in endothelial nitric oxide synthase expression, atherosclerotic plaque stability, pro-inflammatory cytokines and reactive oxygen species production, platelet reactivity, and cardiac fibrosis and hypetrophy development. Recently, statins have been compared to the ezetimibe and the recently published outcomes data on the proprotein convertase subtilisin kexin type 9 inhibitors has allowed for a reexamination of statin pleiotropy. As a result of these diverse effects, it has been suggested that statins also have anti-arrhythmic effects. This review focuses on the mechanisms of statin pleiotropy and discusses evidence from the statin clinical trials as well as examining the possible anti-arrhythmic effects atrial fibrillation and ventricular tachyarrhythmias.",
keywords = "Atrial fibrillation, Cholesterol, Coronary artery disease, Low density lipoprotein, Pleiotropy, Statins, Stroke",
author = "Adam Oesterle and Liao, {James K.}",
year = "2019",
month = "1",
day = "1",
doi = "10.2174/1570161116666180817155058",
language = "English (US)",
volume = "17",
pages = "222--232",
journal = "Current Vascular Pharmacology",
issn = "1570-1611",
publisher = "Bentham Science Publishers B.V.",
number = "3",

}

TY - JOUR

T1 - The pleiotropic effects of statins – From coronary artery disease and stroke to atrial fibrillation and ventricular tachyarrhythmia

AU - Oesterle, Adam

AU - Liao, James K.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Statins, 3-hydroxy-methylglutaryl coenzyme A reductase inhibitors, have been used for decades for the prevention of coronary artery disease and stroke. They act primarily by lowering serum cholesterol through the inhibition of cholesterol synthesis in the liver, which results in the upregulation of low-density lipoprotein receptors in the liver. This results in the removal of low-density lipoprotein-cholesterol. Studies have suggested that statins may demonstrate additional effects that are independent of their effects on low-density lipoprotein-cholesterol. These have been termed “pleiotropic” effects. Pleiotropic effects may be due to the inhibition of isoprenoid intermediates by statins. Isoprenoid inhibition has effects on the small guanosine triphosphate binding proteins Rac and Rho which in turn effects nicotinamide adenine dinucleotide phosphate oxidases. Therefore, there are changes in endothelial nitric oxide synthase expression, atherosclerotic plaque stability, pro-inflammatory cytokines and reactive oxygen species production, platelet reactivity, and cardiac fibrosis and hypetrophy development. Recently, statins have been compared to the ezetimibe and the recently published outcomes data on the proprotein convertase subtilisin kexin type 9 inhibitors has allowed for a reexamination of statin pleiotropy. As a result of these diverse effects, it has been suggested that statins also have anti-arrhythmic effects. This review focuses on the mechanisms of statin pleiotropy and discusses evidence from the statin clinical trials as well as examining the possible anti-arrhythmic effects atrial fibrillation and ventricular tachyarrhythmias.

AB - Statins, 3-hydroxy-methylglutaryl coenzyme A reductase inhibitors, have been used for decades for the prevention of coronary artery disease and stroke. They act primarily by lowering serum cholesterol through the inhibition of cholesterol synthesis in the liver, which results in the upregulation of low-density lipoprotein receptors in the liver. This results in the removal of low-density lipoprotein-cholesterol. Studies have suggested that statins may demonstrate additional effects that are independent of their effects on low-density lipoprotein-cholesterol. These have been termed “pleiotropic” effects. Pleiotropic effects may be due to the inhibition of isoprenoid intermediates by statins. Isoprenoid inhibition has effects on the small guanosine triphosphate binding proteins Rac and Rho which in turn effects nicotinamide adenine dinucleotide phosphate oxidases. Therefore, there are changes in endothelial nitric oxide synthase expression, atherosclerotic plaque stability, pro-inflammatory cytokines and reactive oxygen species production, platelet reactivity, and cardiac fibrosis and hypetrophy development. Recently, statins have been compared to the ezetimibe and the recently published outcomes data on the proprotein convertase subtilisin kexin type 9 inhibitors has allowed for a reexamination of statin pleiotropy. As a result of these diverse effects, it has been suggested that statins also have anti-arrhythmic effects. This review focuses on the mechanisms of statin pleiotropy and discusses evidence from the statin clinical trials as well as examining the possible anti-arrhythmic effects atrial fibrillation and ventricular tachyarrhythmias.

KW - Atrial fibrillation

KW - Cholesterol

KW - Coronary artery disease

KW - Low density lipoprotein

KW - Pleiotropy

KW - Statins

KW - Stroke

UR - http://www.scopus.com/inward/record.url?scp=85061800451&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85061800451&partnerID=8YFLogxK

U2 - 10.2174/1570161116666180817155058

DO - 10.2174/1570161116666180817155058

M3 - Review article

C2 - 30124154

AN - SCOPUS:85061800451

VL - 17

SP - 222

EP - 232

JO - Current Vascular Pharmacology

JF - Current Vascular Pharmacology

SN - 1570-1611

IS - 3

ER -