Lipid-lowering drug use is associated with reduced prevalence of atrial fibrillation in patients with left ventricular systolic dysfunction

doi:10.1016/j.hrthm.2006.05.010

Heart Rhythm

Volume 3, Issue 8, August 2006, Pages 881-886

https://doi.org/10.1016/j.hrthm.2006.05.010 Get rights and content

Background

Inflammation and oxidative stress have been implicated in the pathogenesis of atrial fibrillation (AF). Lipid-lowering drugs, particularly statins and fibrates, possess anti-inflammatory and antioxidant properties.

Objectives

The purpose of this study was to assess the impact of lipid-lowering drug use on AF prevalence in patients with reduced left ventricular ejection fraction (LVEF).

Methods

Data were obtained from ADVANCENT^SM, a multicenter registry of patients with reduced LVEF (≤40%). Demographic, clinical, and echocardiographic parameters were collected from interviews and medical records. Medications, including lipid-lowering drugs, were recorded.

Results

Of the 25,268 patients, 71.3% had hyperlipidemia, and 66.8% were prescribed lipid-lowering drugs. AF prevalence was 25.1% in patients taking lipid-lowering drugs compared with 32.6% in untreated hyperlipidemic patients and 32.8% in patients without hyperlipidemia (P <.001 for both comparisons). In multivariable analysis, lipid-lowering drug use remained significantly associated with reduced odds of AF (odds ratio [OR] 0.69, 95% confidence interval [CI] 0.64–0.74), and this effect was larger than that of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (OR 0.85, 95% CI 0.79–0.92) or β-blockers (OR 0.95, 95% CI 0.88–1.02). The beneficial impact of lipid-lowering drugs on AF risk was independent of their effects on the lipid profile. In patients in whom data on specific lipid-lowering drugs were available, 92% of the patients undergoing lipid-lowering therapy received statins, and 98% received statins and/or fibrates.

Conclusion

Use of lipid-lowering drugs in patients with reduced LVEF is associated with a significant reduction in the prevalence of AF independent of the lipid profile and other known arrhythmia risk factors. This effect is larger than that of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers or β-blockers and may be the result of the antioxidant and anti-inflammatory effects of statins and fibrates.

Introduction

Atrial fibrillation (AF) worsens morbidity and mortality in patients with reduced left ventricular (LV) systolic function.1, 2 Data suggest an association among inflammation, increased oxidative stress, and AF.

Examination of atrial tissue in patients with AF shows infiltration by inflammatory cells³ and increased levels of reactive oxygen species compared with controls.⁴ In addition, higher levels of serologic markers of inflammation, particularly C-reactive protein, have been associated with the presence of AF, an increased arrhythmia burden, and reduced success of cardioversion.5, 6, 7 Modulation of the inflammatory and oxidative milieu with corticosteroids or ascorbic acid has been shown to decrease the risk of AF after cardiac surgery and to reduce early recurrence after successful electrical cardioversion.8, 9 Lipid-lowering drugs, particularly 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), have demonstrated pharmacologic properties independent of their beneficial effects on the lipid profile. These drugs possess anti-inflammatory and antioxidative properties, and they are increasingly being considered as novel antiarrhythmic drugs. Preliminary animal and human data suggest a protective effect of statins on AF risk. In the sterile pericarditis¹⁰ and the atrial rapid-pacing canine model of AF,¹¹ treatment with statins resulted in decreased inducibility and sustainability of the arrhythmia, with associated reductions in serologic and tissue markers of inflammation and decreased electrical remodeling (AF-induced shortening of the atrial action potential). In patients with lone AF, statin use reduced the risk of arrhythmia recurrence following cardioversion¹² and reduced the development of new AF in patients with coronary artery disease independent of cholesterol levels.¹³ Although encouraging, these human studies remain limited by their sample size and by the characteristics of the patients enrolled.

Emerging data also support a role for fibrates in the modulation of inflammation, through activation of the peroxisome proliferator-activated receptor α (PPAR_α). This group of drugs reduces the serum levels and cellular expression of inflammatory mediators in animal models of hypertension and hyperlipidemia and decreases the risk of major cardiovascular events in humans with coronary artery disease.14, 15, 16, 17

In this study, we evaluated the effect of lipid-lowering drugs on AF prevalence in a cohort with reduced LV systolic function. Given the 5- to 10-fold higher risk of AF in this group compared with the general population,¹⁸ successful preventive strategies would have a large health impact.

Section snippets

Study population

Patients enrolled in the ADVANCENT^SM registry (National Registry to Advance Heart Health) through September 30, 2004, were included in the study. ADVANCENT^SM is a multicenter, observational registry designed to collect and report data on the histories, diagnostics, therapies, and interventions for patients with LV dysfunction (left ventricular ejection fraction [LVEF] ≤40%). This registry, designed to collect detailed medical and demographic information to assist physicians in identifying gaps

Results

The baseline characteristics of the 25,268 patients included in this study are detailed in our previous publication¹⁹ and are partially listed in Table 1. Mean patient age was 66.4 years. Coronary artery disease was the etiologic factor of the cardiomyopathy in 72.1% of subjects. Mean LVEF was 31%, with more than half of the patients in NYHA heart failure class II. Comorbid conditions included hypertension (72.4%), hyperlipidemia (71.3%), and diabetes mellitus (31.3%). The proportion of the

Discussion

In this study, we evaluated the impact of lipid-lowering drugs on AF prevalence in a large population of patients with reduced LV function. As expected for this cohort, there was a high prevalence of AF (28%) as well as hypertension, hyperlipidemia, and diabetes mellitus. We showed that the use of lipid-lowering drug was associated with a significant reduction in the odds of AF (31% relative reduction). This effect was more than that from ACEIs/ARBs or β-blockers and was independent of known AF

Conclusion

Our data suggest that lipid-lowering drug use is associated with a significant reduction in AF risk in patients with low LVEF at high risk for the arrhythmia; this reduction was the most sizeable among known prophylactic pharmacotherapies. The role of lipid-lowering drugs in the treatment of preexisting AF is not elucidated by this study and remains controversial.12, 39

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Original-clinicalLipid-lowering drug use is associated with reduced prevalence of atrial fibrillation in patients with left ventricular systolic dysfunction

Background

Objectives

Methods

Results

Conclusion

Introduction

Section snippets

Study population

Results

Discussion

Conclusion

Int J Cardiol

J Thorac Cardiovasc Surg

Am J Cardiol

Am J Cardiol

J Mol Cell Cardiol

Blood

J Biol Chem

J Am Coll Cardiol

J Am Coll Cardiol

J Pharmacol Sci

Am J Cardiol

J Biol Chem

Am J Cardiol

Impact of atrial fibrillation on the risk of deaththe Framingham Heart Study

Circulation

Temporal relations of atrial fibrillation and congestive heart failure and their joint influence on mortalitythe Framingham Heart Study

Circulation

Histological substrate of atrial biopsies in patients with lone atrial fibrillation

Circulation

Impaired myofibrillar energetics and oxidative injury during human atrial fibrillation

Circulation

Inflammation as a risk factor for atrial fibrillation

Circulation

C-reactive protein and paroxysmal atrial fibrillationevidence of the implication of an inflammatory process in paroxysmal atrial fibrillation

Acta Cardiol

Original-clinical
Lipid-lowering drug use is associated with reduced prevalence of atrial fibrillation in patients with left ventricular systolic dysfunction