High Sensitivity C-Reactive Protein Predicts Recurrence of Atrial Fibrillation
Abstract & Commentary
By John P. DiMarco, MD, PhD, Professor of Medicine, Division of Cardiology, University of Virginia, Charlottesville. Dr. DiMarco is a consultant for Novartis, and does research for Medtronic and Guidant.
Synopsis: These data, indicating that high levels of CRP are associated with an increased risk of recurrence, support the concept that systemic inflammation is important for the pathogenesis of atrial fibrillation.
Source: Malouf JF, et al. High Sensitivity C-Reactive Protein: A Novel Predictor for Recurrence of Atrial Fibrillation After Successful Cardioversion. J Am Coll Cardiol. 2005;46:1284-1287.
In this paper, Malouf and colleagues from the Mayo Clinic looked at the significance of C-reactive protein (CRP) levels on the recurrence of atrial fibrillation or atrial flutter after a successful cardioversion. In 67 patients referred for cardioversion, high-sensitivity CRP was measured in patients prior to the procedure. Patients with previous cardioversions, recent infections, recent coronary surgery, or an acute coronary syndrome were excluded. CRP values were then included with other variables in a logistic regression model to identify univariate and multivariate predictors for recurrence of arrhythmia within one month after cardioversion. A large number of patient characteristics were included in the model, and stepwise linear regression was used first to identify univariate predictors of recurrence. Variables that were determined to be associated with recurrence in the first step were then included in a multivariate analysis. In the final step, the association of CRP levels was assessed after adjusting for the variables determined to show a relationship in the first and second steps.
Before cardioversion, the estimated duration of the arrhythmia was less than one month in 52% of the patients and more than one month in 48%. Only 2 patients had been in atrial fibrillation for more than one year. At the one month follow-up, 22 patients (33%) had recurrence of atrial fibrillation or atrial flutter. Pre-cardioversion CRP levels were associated with arrhythmia recurrence, even after adjusting for age, gender, and duration of arrhythmia. Other univariate predictors of arrhythmia recurrence included a higher pre-cardioversion mean heart rate, pre-cardioversion use of class 1C antiarrhythmic drugs, or calcium channel blockers. An increase in the frequency of recurrent arrhythmia was also noted among patients discharged on nondihydropyridine channel blockers. A trend towards less arrhythmia recurrence was seen among patients discharged on beta blockers. Interestingly, Malouf and colleagues report that left ventricular ejection fraction, the presence of valvular heart disease, pre-conversion usage of angiotensin receptor blockers, angiotensin converting enzyme inhibitors, amiodarone, sotalol, and digoxin were not predictors of recurrence. Unfortunately, the influence of any post-discharge antiarrhythmic drugs is not clearly reported. On multivariate analysis, pre-cardioversion CRP was the only independent predictor of recurrence, with an odds ratio of 2.19 (95% confidence interval 1.05 to 4.55; P = 0.036). Malouf et al suggest that their data, indicating that high levels of CRP are associated with an increased risk of recurrence, support the concept that systemic inflammation is important for the pathogenesis of atrial fibrillation.
This is an interesting report that, although it does not provide definite data, should lead to further studies investigating the role of inflammation in the pathogenesis and maintenance of atrial fibrillation. There has been increasing interest in the role of the atrial endocardium in atrial fibrillation, and inflammation is one of the possible factors that might promote changes which favor atrial fibrillation.
The major limitation in this study is the very large number of variables examined in a relatively small population. Numerous, large studies of antiarrhythmic therapy have shown that sotalol, amiodarone, or other antiarrhythmic drugs are more effective than placebo in preventing recurrences of atrial fibrillation. Malouf et al report that there was not a relationship with amiodarone or sotalol therapy, but it seems likely that most patients were discharged on antiarrhythmics, and the study was not large enough to differentiate between 2 effective agents. The same logic may well pertain to this study's inability to show an effect from angiotensin receptor blockers and angiotensin converting enzyme inhibitors, agents shown to help prevent recurrent atrial fibrillation in other reports. One would anticipate that many of the patients were discharged on these agents and, therefore, one could not see whether these truly had an effect on recurrence.
We must also remember that merely identifying a risk factor for an adverse clinical outcome does not always mean that treatment directed against the risk factor will produce benefit. However, the observations here, and in other studies, seem promising and should lead to the next level of clinical trials.