Cardiac Autonomic Dysfunction and Incidence of Atrial Fibrillation: Results From 20 Years Follow-Up

Abstract

Background: Cardiac autonomic perturbations frequently antecede onset of paroxysmal atrial fibrillation (AF). Interventions that influence autonomic inputs to myocardium may prevent AF. However, whether low heart rate or heart rate variability (HRV), which are noninvasive measures of cardiac autonomic dysfunction, are associated with AF incidence is unclear.

Objectives: This study sought to study the association between HRV and risk of AF.

Methods: This study included 11,715 middle-aged adults in the ARIC (Atherosclerosis Risk In Communities) cohort with heart rate and HRV measures obtained from 2-min electrocardiogram recordings performed at baseline (1987 to 1989). These measures included SD of normal-to-normal RR intervals, high-frequency (HF) (0.15 to 0.40 Hz), low-frequency (0.04 to 0.15 Hz), and the low-frequency/HF ratio (denoting a greater sympathetic to parasympathetic dominance). Incident AF cases were ascertained by electrocardiogram at ARIC follow-up visits, hospital discharge diagnosis, or death certificates through 2011.

Results: During an average follow-up of 19.4 years, 1,580 or 13.5% of participants developed AF. A baseline heart rate <60 beats/min was associated modestly with an increased risk of AF. Lower overall HRV as well as increased sympathetic/parasympathetic tone were associated independently with a higher risk of AF; the hazard ratio for each 1 SD lower SD of normal-to-normal RR intervals was 1.14 (95% confidence interval: 1.08 to 1.21), for HF was 1.12 (95% confidence interval: 1.06 to 1.17), and for low frequency/HF was 1.08 (95% confidence interval: 1.03 to 1.14).

Conclusions: Cardiac autonomic dysfunction denoted by low resting short-term HRV was associated with higher AF incidence. A low heart rate may be associated with higher AF risk. Further studies are needed to determine whether interventions in the general population to restore autonomic balance may prevent AF.

Keywords: arrhythmia; frequency; heart rate variability; parasympathetic; sympathetic.

Central Illustration. Cardiac Autonomic Function and Atrial Fibrillation: Potential Interplay

Abnormalities in cardiac autonomic function, as denoted by a lower heart rate variability (HRV) or unbalanced sympathetic to parasympathetic tone, were associated with a higher risk of developing atrial fibrillation (AF) in a population-based cohort over 20 years of follow-up. Future studies should investigate whether modulation of the autonomic nervous system, through strategies such as weight management, exercise, and yoga, may be effective in preventing AF. **One SDNN lower HRV measure was associated with 21% higher risk of AF development over 20 years of follow up in the ARIC study cohort. Abbreviations: ARIC = Atherosclerosis Risk in Communities; A-V = atrioventricular; HF = high frequency; LF = low frequency; S-A = sino-atrial; SDNN = standard deviation of normal-to-normal R-R intervals.

Figure 1. Baseline RR Interval and Incident AF

The dose-response relationship of inverse heart rate and incident atrial fibrillation (AF) showed a threshold effect around 1,200 ms. The model was adjusted for baseline age, race, sex, diabetes, hypertension, high- and low-density lipoprotein cholesterol, prevalent coronary heart disease, prevalent heart failure, current smoking status, alcohol drinking, and body mass index. Although, the shape of the relationship remained unchanged after additional adjustment for beta-blockers, the confidence interval (CI) widened.

Figure 2. HRV and AF Incidence

The multivariable-adjusted dose-response relationship between HRV measures (SDNN and high frequency) with incident AF suggested an almost log linear relationship with threshold effect between incident AF and (A) standard deviation normal to normal (SDNN) and (B) high frequency, both measures of HRV. The curves were adjusted for prevalent coronary heart disease, diabetes, hypertension, prevalent heart failure, smoking status, alcohol intake, education level, high- and low-density lipoprotein cholesterol, study center, body mass index, heart rate, and Cornell voltage. Abbreviations as in Figure 1.