REM Sleep Imposes a Vascular Load in COPD Patients Independent of Sleep Apnea

ABSTRACT

Arterial stiffness, a marker for cardiovascular risk, is increased in patients with Chronic Obstructive Pulmonary Disease (COPD) and Obstructive Sleep Apnea (OSA). The specific influence of both on arterial stiffness during sleep is unknown. Nocturnal arterial stiffness (Pulse Propagation Time (PPT) of the finger pulse wave) was calculated in 142 individuals evaluated for sleep apnea: 27 COPD patients (64.7 ± 11y, 31.2 ± 8 kg/m²), 72 patients with cardiovascular disease (CVD group, 58.7 ± 13y, 33.6 ± 6 kg/m²) and 43 healthy controls (HC group 49.3 ± 12y, 27.6 ± 3 kg/m²). Sleep stage related PPT changes were assessed in a subsample of COPD patients and matched controls (n = 12/12). Arterial stiffness during sleep was increased in COPD patients (i.e. shortened PPT) compared to healthy controls (158.2 ± 31 vs. 173.2 ± 38 ms, p = 0.075) and to patients with CVD (161.4 ± 41 ms). Arterial stiffening was particular strong during REM sleep (145.9 ± 28 vs. 172.4 ± 43 ms, COPD vs. HC, p = 0.003). In COPD, time SaO₂ < 90% was associated with reduced arterial stiffness (Beta +1.7 ms (1.1–2.3)/10 min, p < 0.001). Sleep apnea did not affect PPT. In COPD, but not in matched controls, arterial stiffness increased from wakefulness to REM-sleep (ΔPPT-8.9 ± 10% in COPD and 3.7 ± 12% in matched controls, p = 0.021). Moreover, REM-sleep related arterial stiffening was correlated with elevated daytime blood pressure (r = −0.92, p < 0.001) and increased myocardial oxygen consumption (r = −0.88, p < 0.01). Hypoxia and REM sleep modulate arterial stiffness. In contrast to healthy controls, REM sleep imposes a vascular load in COPD patients independent of sleep apnea indices, intermittent and sustained hypoxia. The link between REM-sleep, vascular stiffness and daytime cardiovascular function suggests that REM-sleep plays a role for increased cardiovascular morbidity of COPD patients.

KEYWORDS:

• REM sleep
• COPD
• arterial stiffness
• cardiovascular risk
• blood pressure
• nocturnal hypoxia

Acknowledgments

Contribution: The corresponding author (LG) takes responsibility for the content of the manuscript, including the data and analysis. All co-authors except for HS were involved in the collection of data. LG and HS planned and performed the data analysis, they also wrote the first draft of the manuscript. All co-authors reviewed the data and were involved in the preparation of the final manuscript.

Funding sources of the study: This study was supported by the Swedish Heart and Lung Foundation (HLF 20110445, 20120429 and 20130488), the German Ministry for Education and Science (BMBF), the National Institute of Health (R01 HL105546), and Weinmann Geräte für Medizin GmbH&Co.KG.

Declaration of interest

1.	Dr. Grote reports personal fees from Weinmann GMBH and grants from the Swedish Heart and Lung Foundation during the conduct of the study; personal fees from Resmed, Philips, Mundipharma, and Breas as well as grants from the Resmed and Philips Foundations outside the submitted work.
2.	Dr. Hedner reports grants from ResMed, grants from Phillips Respironics, payments related to speaker activities from AstraZeneca, Novartis, Takeda and Jazz Pharmaceuticals outside the submitted work.
3.	Dr. Fietze reports personal fees from Somnomed and grant support from Heinen and Löwenstein, Philips, Resmed, Weinmann and Hoffrichter.
4.	Dr. Penzel is shareholder of The Siestagroup GmbH and Advanced Sleep Research. His institution has received grants from Cidelec, Apnex, Imthera, Itamar, Nomics, Heinen and Löwenstein, Philips, Resmed, Weinmann.
5.	Dr. Randerath reports personal fees from Inspire, personal fees from Philips Respironics, personal fees from Resmed, personal fees from Weinmann, outside the submitted work.
6.	Dr. Sanner reports grants from Weinmann outside the submitted work.
7.	Dr. Ficker reports personal fees from Weinmann during the conduct of the study.
8.	Dr. Schneider reports personal fees from Linde Healthcare, TNI Medical, Fisher & Paykel Healthcare, InSleep, Philipps Respironics, Apnex. My institution has received grants from Imthera, Resmed, InSleep, TNI Medical and Fisher & Paykel Healthcare.
9.	Dr. Sommermeyer has nothing to disclose.