Abnormal Sleep-Cardiovascular System Interaction in Narcolepsy with Cataplexy: Effects of Hypocretin Deficiency in Humans

Study Objective: Narcolepsy with cataplexy (NC) is associated with loss of hypocretin neurons in the lateral hypothalamus involved in the circadian timing of sleep and wakefulness, and many biologic functions including autonomic control. The authors investigated whether chronic lack of hypocretin signaling alters cardiovascular control during sleep in humans. Design: Comparison of 24-hr circadian rhythms, day-night, time-and state-dependent changes of blood pressure (BP) and heart rate (HR) in drug-free patients with NC and control subjects. Setting: University hospital. Patients or Participants: Ten drug-free patients with NC (9 men, 1 woman) and 12 control subjects (9 men, 3 women). Interventions: N/A. Measurements and Results: Daytime BP was comparable in patients with NC and controls, but patients with NC displayed a nighttime nondipping BP pattern. The 24-hr circadian rhythmicity of BP and HR was normal in both groups. Systolic BP during nighttime rapid eye movement sleep was significantly increased in the NC group. The 24-hr HR was significantly higher in the NC group but the day-night and state-dependent HR modulations were intact. The nighttime BP pattern coupled in the NC group with increased sleep fragmentation and a higher prevalence of arousals, periodic limb movements in sleep (PLMS), and PLMS arousals. In an analysis of the sleep/cardiovascular interaction in the periods after sleep onset and preceding morning awakening, only PLMS were consistently associated with the blunted nighttime decrease in BP in the NC group. Conclusions: Hypocretin deficiency in humans may couple with an altered nighttime BP regulation that can be associated with an increased cardiovascular risk. This finding may be the result not only of the hypocretinergic deficiency per se but also of the altered sleep/wake regulation characterizing NC.