Impaired cardiac autonomic function, measured by heart rate variability (HRV), is associated with an increased exacerbation risk and symptom burden in patients with chronic obstructive pulmonary disease (COPD), according to a study in Chronic Obstructive Pulmonary Diseases.

Researchers used data from the CLEAN AIR Heart Study to assess the association between HRV and markers of COPD morbidity among former smokers with moderate to severe COPD.

Participants from a single urban center underwent clinical evaluation at baseline, 1 week, 3 months, and 6 months. Some participants completed 24-hour Holter monitoring in each 1-week period to assess HRV.

The main HRV measures of interest were the standard deviation of normal to normal intervals (SDNN), overall HRV, and the root-mean square of successive differences (RMSSD). The association between HRV and exacerbation risk was evaluated in zero-inflated negative binomial models, and associations between HRV indices and respiratory symptom measures were assessed in mixed-effects models.

HRV may represent an important noninvasive biomarker with the potential to identify high-risk populations with COPD.

The analysis included 85 participants with 305 Holter measurements in addition to health outcomes. Participants’ mean (SD) age was 65.6 (8.6) years, 53% were female, and their mean pack-years of smoking was 51.8 (32.6). The mean number of exacerbations per participant was 1.33 (2.29) for any exacerbation and 0.37 (0.80) for severe exacerbations during the 6-month follow-up.

A significant association between HRV and exacerbation risk was observed in adjusted models. A reduction in SDNN, low frequency power, and high frequency power were associated with a greater risk for future COPD exacerbations, which was driven primarily by severe exacerbations, with a decrease in all HRV measures including SDNN (incidence rate ratio [IRR] 1.40; 95% CI, 1.13-1.74) and RMSSD (IRR 1.60; 95% CI, 1.07-2.37) associated with severe exacerbations.

Decreased HRV, according to SDNN, was associated with worsened COPD symptom measures, including St George’s Respiratory Questionnaire (SGRQ) and COPD Assessment Test (CAT) scores. In addition, lower SDNN was associated with higher odds of chronic bronchitis in the SGRQ (odds ratio [OR] 1.21; 95% CI, 1.06-1.38) and CAT (OR 1.19; 95% CI, 1.04-1.36).

Study limitations include a small population, which reduced researchers’ ability to extrapolate the results to other groups and to conduct subgroup analyses. Also, the investigators were unable to account for measures of hypoxemia, including nocturnal hypoxemia, which can affect HRV and lead to cardiovascular morbidity in patients with COPD.

“HRV may represent an important noninvasive biomarker with the potential to identify high-risk populations with COPD,” stated the researchers. “Future studies are warranted to confirm the relationship between HRV and multimorbidity in COPD across diverse populations.”

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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