Dissociation of Objective and Subjective Daytime Sleepiness and Biomarkers of Systemic Inflammation in Sleep-Disordered Breathing and Systolic Heart Failure

J Clin Sleep Med. 2017 Dec 15;13(12):1411-1422. doi: 10.5664/jcsm.6836.

Abstract

Study objectives: Subjective versus objective sleepiness in heart failure (HF) remains understudied; therefore, we sought to examine the association of these measures and interrelationships with biochemical markers.

Methods: Participants with stable systolic HF recruited from a clinic-based program underwent attended polysomnography, Multiple Sleep Latency Testing, questionnaire data collection including Epworth Sleepiness Scale (ESS), and morning phlebotomy for biochemical markers. Linear regression was used to assess the association of mean sleep latency (MSL) and ESS (and other reported outcomes) with adjustment of age or body mass index or left ventricular ejection fraction (LVEF) (beta coefficients, 95% confidence interval) and also with biochemical markers (beta coefficients, 95% confidence interval).

Results: The final analytic sample comprised 26 participants: 52 ± 14 years with apnea-hypopnea index (AHI): 34 ± 27, LVEF: 34 ± 12%, MSL: 7 ± 5 minutes and ESS: 7 (5, 10). There was no significant association of MSL and ESS (-0.36, -0.81 to 0.09, P = .11), AHI, or other questionnaire-based outcomes in adjusted analyses. Although statistically significant associations of ESS and biomarkers were not observed, there were associations of MSL and cortisol (μg/dL) [-0.05: -0.08, -0.01, P = .012] and interleukin-6 (pg/mL) [-0.11: -0.18, -0.04, P = .006], which persisted in adjusted models.

Conclusions: In systolic HF, although overall objective sleepiness was observed, this was not associated with subjective sleepiness (ie, a discordance was identified). Differential upregulation of systemic inflammation in objective sleepiness was observed, findings not observed with subjective sleepiness. These findings suggest that underlying mechanistic pathways of inflammation may provide the explanation for dissonance of objective and subjective sleepiness symptoms in HF, thus potentially informing targeted diagnostic and therapeutic approaches.

Commentary: A commentary on this article appears in this issue on page 1369.

Keywords: biomarkers; heart failure; sleep apnea; sleepiness; systemic inflammation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biomarkers / blood
  • Disorders of Excessive Somnolence / blood
  • Disorders of Excessive Somnolence / complications*
  • Disorders of Excessive Somnolence / physiopathology*
  • Female
  • Heart Failure, Systolic / blood
  • Heart Failure, Systolic / complications*
  • Heart Failure, Systolic / physiopathology
  • Humans
  • Hydrocortisone / blood
  • Inflammation / blood*
  • Inflammation / complications*
  • Inflammation / physiopathology
  • Male
  • Middle Aged
  • Polysomnography
  • Sleep Apnea Syndromes / blood
  • Sleep Apnea Syndromes / complications*
  • Sleep Apnea Syndromes / physiopathology
  • Sleep Latency
  • Surveys and Questionnaires

Substances

  • Biomarkers
  • Hydrocortisone