Original-clinicalLipid-lowering drug use is associated with reduced prevalence of atrial fibrillation in patients with left ventricular systolic dysfunction
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 (PPARα). 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 ADVANCENTSM registry (National Registry to Advance Heart Health) through September 30, 2004, were included in the study. ADVANCENTSM 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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