Abnormally high exertional breathlessness predicts mortality in people referred for incremental cycle exercise testing

PLoS One. 2024 Dec 18;19(12):e0302111. doi: 10.1371/journal.pone.0302111. eCollection 2024.

Abstract

Background: Exertional breathlessness is a key symptom in cardiorespiratory disease and can be quantified using incremental exercise testing, but its prognostic significance is unknown. We evaluated the ability of abnormally high breathlessness intensity during incremental cycle exercise testing to predict all-cause, respiratory, and cardiac mortality.

Study design and methods: Longitudinal cohort study of adults referred for exercise testing followed prospectively for mortality assessed using the Swedish National Causes of Death Registry. Abnormally high exertional breathlessness was defined as a breathlessness intensity response (Borg 0-10 scale) > the upper limit of normal using published reference equations. Mortality was analyzed using multivariable Cox regression, unadjusted and adjusted for age, sex, and body mass index. A further mortality analysis was also done adjusted for select common comorbidities in addition to age, sex and body mass index.

Results: Of the 13,506 people included (46% female, age 59±15 years), 2,867 (21%) had abnormally high breathlessness during exercise testing. Over a median follow up of 8.0 years, 1,687 (12%) people died. No participant was lost to follow-up. Compared to those within normal predicted ranges, people with abnormally high exertional breathlessness had higher mortality from all causes (adjusted hazard ratio [aHR] 2.3, [95% confidence interval] 2.1-2.6), respiratory causes (aHR 5.2 [3.4-8.0]) and cardiac causes (aHR 3.0 [2.5-3.6]). Even among people with normal exercise capacity (defined as peak Watt ≥75% of predicted exercise capacity, n = 10,284) those with abnormally high exertional breathlessness were at greater risk of all-cause mortality than people with exertional breathlessness within the normal predicted range (aHR 1.5 [1.2-1.8]).

Conclusion: Among people referred for exercise testing, abnormally high exertional breathlessness, quantified using healthy reference values, independently predicted all-cause, respiratory and cardiac mortality.

MeSH terms

  • Adult
  • Aged
  • Dyspnea* / diagnosis
  • Dyspnea* / mortality
  • Dyspnea* / physiopathology
  • Exercise Test*
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Sweden / epidemiology

Grants and funding

VE was funded by an unrestricted grant from the Scientific Committee of Blekinge Region. DJ holds a Canada Research Chair, Tier II, in Clinical Exercise and Respiratory Physiology from the Canadian Institutes of Health Research. ME was supported by unrestricted grants from the Swedish Society for Medical Research and the Swedish Research Council (Dnr: 2019-02081). HL is supported by a fellowship from the NHMRC Centre of Research Excellence in Treatable Traits. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.