Attenuated heart rate response is associated with hypocretin deficiency in patients with narcolepsy

Sleep. 2013 Jan 1;36(1):91-8. doi: 10.5665/sleep.2308.

Abstract

Study objective: Several studies have suggested that hypocretin-1 may influence the cerebral control of the cardiovascular system. We analyzed whether hypocretin-1 deficiency in narcolepsy patients may result in a reduced heart rate response.

Design: We analyzed the heart rate response during various sleep stages from a 1-night polysomnography in patients with narcolepsy and healthy controls. The narcolepsy group was subdivided by the presence of +/- cataplexy and +/- hypocretin-1 deficiency.

Setting: Sleep laboratory studies conducted from 2001-2011.

Participants: In total 67 narcolepsy patients and 22 control subjects were included in the study. Cataplexy was present in 46 patients and hypocretin-1 deficiency in 38 patients.

Interventions: None.

Measurements and results: All patients with narcolepsy had a significantly reduced heart rate response associated with arousals and leg movements (P < 0.05). Heart rate response associated with arousals was significantly lower in the hypocretin-1 deficiency and cataplexy groups compared with patients with normal hypocretin-1 levels (P < 0.04) and patients without cataplexy (P < 0.04). Only hypocretin-1 deficiency significantly predicted the heart rate response associated with arousals in both REM and non-REM in a multivariate linear regression.

Conclusions: Our results show that autonomic dysfunction is part of the narcoleptic phenotype, and that hypocretin-1 deficiency is the primary predictor of this dysfunction. This finding suggests that the hypocretin system participates in the modulation of cardiovascular function at rest.

MeSH terms

  • Adult
  • Arousal
  • Autonomic Nervous System / physiopathology*
  • Female
  • Heart Rate*
  • Humans
  • Intracellular Signaling Peptides and Proteins / deficiency*
  • Male
  • Narcolepsy / diagnosis
  • Narcolepsy / physiopathology*
  • Neuropeptides / deficiency*
  • Orexins
  • Polysomnography / methods
  • Sleep Stages

Substances

  • HCRT protein, human
  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexins