Muscle sympathetic nerve activity in COPD: a systematic review and meta-analysis

Clinical Snapshot

Key Findings

• P Value: Not reported in abstract

• Effect Size: Mean difference +18.5 bursts·min⁻¹ for burst frequency, +21.3 bursts per 100 heartbeats for burst incidence

• Primary Outcome: MSNA burst frequency significantly higher in COPD vs controls

• Nnt Or Sensitivity: Effect size represents substantial sympathetic overactivity (approximately 50-60% increase based on typical control values)

• Confidence Interval: 95% CI 9.4-27.7 for burst frequency, 95% CI 9.2-33.4 for burst incidence

Clinical Application

MSNA measurement requires specialised microneurography equipment and expertise, limiting routine clinical application Relevant to Australian COPD management under RACGP guidelines; may inform cardiovascular risk stratification and support for sympathetic modulation therapies if available through PBS Adults with established COPD diagnosis confirmed by spirometry

Abstract

BACKGROUND: Cardiovascular disease is a primary driver of mortality in COPD. Elevated sympathetic nerve activity is a key proposed mechanism, but the magnitude of this autonomic overactivity has not been quantified in a pooled analysis. OBJECTIVE: To determine if adults with COPD exhibit higher resting muscle sympathetic nerve activity (MSNA) than healthy controls, assess associated cardiorespiratory effects, and evaluate the short-term impact of COPD interventions on MSNA. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, eight databases were searched from inception to 15 May 2025 to inform this systematic review and meta-analysis (PROSPERO CRD420251044931). Eligible studies included adults with spirometry-defined COPD in whom MSNA was measured by microneurography at rest. Primary outcomes were MSNA burst frequency (bursts·min-1) and incidence (bursts per 100 heartbeats). Secondary outcomes included resting heart rate and blood pressure. RESULTS: A total of 11 studies (171 COPD participants, 105 controls) met inclusion criteria. Compared with controls, COPD was associated with markedly higher MSNA, burst frequency (+18.5, 95% CI 9.4-27.7 bursts·min-1) and burst incidence (+21.3, 95% CI 9.2-33.4 bursts per 100 heartbeats). Resting heart rate was also elevated (+10.7, 95% CI 6.1-15.3 beats·min-1), while blood pressure did not differ significantly. Three studies on noninvasive ventilation or inhaled β2-agonists found no significant pooled changes in MSNA. CONCLUSIONS: Resting MSNA is significantly elevated in patients with COPD despite normal blood pressure. This chronic sympathetic excitation likely contributes to COPD-related cardiovascular morbidity and exercise intolerance, highlighting the importance of developing therapies that reduce sympathetic nerve activity.

References

1. 1.Duiker, B., Shirazi, S., Sivak, A., Stickland, M. K., Davenport, M. H., & Steinback, C. D. (2026). Muscle sympathetic nerve activity in COPD: a systematic review and meta-analysis. European Respiratory Review, 35(140), Article 0267-2025. https://doi.org/10.1183/16000617.0267-2025