Anticholinergics aggravate the imbalance of the autonomic nervous system in stable chronic obstructive pulmonary disease

BACKGROUND: Inhaled anticholinergics, recommended as first-line maintenance treatment for patients with moderate-to-severe chronic obstructive pulmonary disease (COPD), has been demonstrated to be associated with an increased risk of cardiovascular diseases. Nevertheless, why COPD patients using inhaled anticholinergics have this higher risk remains unknown. One of mechanisms may be an autonomic imbalance because anticholinergics yield reduced vagal nervous activity. To test our hypothesis, we studied heart rate recovery (HRR) after exercise, recognized as a marker of cardiac autonomic function, in COPD patients using and not using inhaled anticholinergics. METHODS: Sixty patients with COPD were involved in this study (mean FEV(1) = 1.57 ± 0.42 L), including 24 patients who had received tiotropium for more than 1 year and 36 patients not using tiotropium as a control group. A maximal cardiopulmonary exercise test was performed. HRR was defined as the difference between peak exercise and at 1-min recovery heart rate. RESULTS: HRR was significantly lower in patients using tiotropium than in the controls (16 ± 6 vs 22 ± 8 beats/min, respectively, p < 0.05). Multivariate regression analysis revealed that tiotropium use and peak VCO(2) were independent predictors of HRR in these COPD patients. CONCLUSIONS: These findings suggest that anticholinergics bronchodilators reduce HRR after exercise in COPD patients. This has the potential to aggravate autonomic nervous imbalance. Therefore, we recommend that COPD patients taking anticholinergic bronchodilators should be considered for monitoring of cardiac function and prescribers should be alert for cardiovascular events that may arise from autonomic nervous imbalance.