Incidence of atrial fibrillation in relation to changing heart rate over time in hypertensive patients: the LIFE study

Peter M Okin, Kristian Wachtell, Sverre E Kjeldsen, Stevo Julius, Lars H Lindholm, Björn Dahlöf, Darcy A Hille, Markku S Nieminen, Jonathan M Edelman, Richard B Devereux
Circulation. Arrhythmia and Electrophysiology 2008, 1 (5): 337-43

BACKGROUND: Onset of atrial fibrillation (AF) has been linked to changes in autonomic tone, with increasing heart rate (HR) immediately before AF onset in some patients suggesting a possible role of acute increases in sympathetic activity in AF onset. Although losartan therapy and decreasing ECG left ventricular hypertrophy are associated with decreased AF incidence, the relationship of HR changes over time to development of AF has not been examined.

METHODS AND RESULTS: HR was evaluated in 8828 hypertensive patients without AF by history or on baseline ECG in the Losartan Intervention for End Point Reduction in Hypertension (LIFE) study. Patients were treated with losartan- or atenolol-based regimens and followed with serial ECGs annually which were used to determine HR and ECG left ventricular hypertrophy by Cornell product and Sokolow-Lyon voltage criteria. During mean follow-up of 4.7+/-1.1 years, new-onset AF occurred in 701 patients (7.9%). Patients with new AF had smaller decreases in HR to last in-treatment ECG or last ECG before AF (-2.7+/-13.5 versus -5.2+/-12.5 bpm), whether on losartan- (-0.4+/-13.5 versus -2.2+/-11.7 bpm) or atenolol-based treatment (-5.3+/-12.8 versus -8.3+/-12.6 bpm, all P<0.001). In univariate Cox analyses, higher HR on in-treatment ECGs was associated with an increased risk of new-onset AF, with a 15% greater risk of AF for every 10 bpm higher HR (95% CI 8% to 22%). In alternative analyses, persistence or development of a HR> or =84 (upper quintile of baseline HR) was associated with a 46% greater risk of developing AF (95% CI 19% to 80%). After adjusting for treatment with losartan versus atenolol, baseline risk factors for AF, baseline and in-treatment systolic and diastolic pressure and the known predictive value of baseline and in-treatment ECG left ventricular hypertrophy for new AF, higher in-treatment HR remained strongly associated with new AF with a 19% higher risk for every 10 bpm higher HR (95% CI 10% to 28%) or a 61% increased rate of AF in patients with persistence or development of a HR> or =84 (95% CI 27% to 104%, all P<0.001).

CONCLUSIONS: Higher in-treatment HR on serial ECGs is associated with an increased likelihood of new-onset AF, independent of treatment modality, blood pressure lowering, and regression of ECG left ventricular hypertrophy in patients with essential hypertension.

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