Sleep-Disordered Breathing and Vascular Function in Patients With Chronic Mountain Sickness and Healthy High-Altitude Dwellers

doi:10.1378/chest.15-1450

Chest

Volume 149, Issue 4, April 2016, Pages 991-998

https://doi.org/10.1378/chest.15-1450 Get rights and content

Background

Chronic mountain sickness (CMS) is often associated with vascular dysfunction, but the underlying mechanism is unknown. Sleep-disordered breathing (SDB) frequently occurs at high altitude. At low altitude, SDB causes vascular dysfunction. Moreover, in SDB, transient elevations of right-sided cardiac pressure may cause right-to-left shunting in the presence of a patent foramen ovale (PFO) and, in turn, further aggravate hypoxemia and pulmonary hypertension. We speculated that SDB and nocturnal hypoxemia are more pronounced in patients with CMS compared with healthy high-altitude dwellers, and are related to vascular dysfunction.

Methods

We performed overnight sleep recordings, and measured systemic and pulmonary artery pressure in 23 patients with CMS (mean ± SD age, 52.8 ± 9.8 y) and 12 healthy control subjects (47.8 ± 7.8 y) at 3,600 m. In a subgroup of 15 subjects with SDB, we assessed the presence of a PFO with transesophageal echocardiography.

Results

The major new findings were that in patients with CMS, (1) SDB and nocturnal hypoxemia was more severe (P < .01) than in control subjects (apnea-hypopnea index [AHI], 38.9 ± 25.5 vs 14.3 ± 7.8 number of events per hour [nb/h]; arterial oxygen saturation, 80.2% ± 3.6% vs 86.8% ± 1.7%, CMS vs control group), and (2) AHI was directly correlated with systemic blood pressure (r = 0.5216; P = .001) and pulmonary artery pressure (r = 0.4497; P = .024). PFO was associated with more severe SDB (AHI, 48.8 ± 24.7 vs 14.8 ± 7.3 nb/h; P = .013, PFO vs no PFO) and hypoxemia.

Conclusions

SDB and nocturnal hypoxemia are more severe in patients with CMS than in control subjects and are associated with systemic and pulmonary vascular dysfunction. The presence of a PFO appeared to further aggravate SDB. Closure of the PFO may improve SDB, hypoxemia, and vascular dysfunction in patients with CMS.

Trial Registry

ClinicalTrials.gov; No.: NCT01182792; URL: www.clinicaltrials.gov;

Section snippets

Materials and Methods

Between August 2008 and August 2010, 23 male patients with CMS (mean ± SD age, 52.8 ± 9.8 y) and 12 healthy high-altitude dwellers (47.8 ± 7.8 y) without traditional pulmonary and cardiovascular risk factors (smoking, arterial hypertension, hypercholesterolemia, or diabetes) or a family history of premature cardiovascular events, hypertension, or diabetes, who were born at and had been permanently living at high altitude (3,600-4,000 m), were included in the study. Inclusion criteria for

Results

The characteristics of the study participants are presented in Table 1. By definition, CMS score, hemoglobin, and hematocrit were markedly higher in patients with CMS compared with healthy high-altitude dwellers. BMI was higher in patients with CMS (29.5 ± 3.0 kg/m² vs 26.6 ± 3.1 kg/m²; P = .02, CMS vs control group). Lung function and systemic blood pressure were normal and comparable in the two groups.

Discussion

CMS, a major health problem affecting several million people worldwide, is associated with vascular dysfunction,7, 18 but the underlying mechanism is incompletely understood. High altitude alters nocturnal breathing, and at low altitude, altered nocturnal respiration is associated with altered vascular function. We found that patients with CMS display more severe SDB and nocturnal oxygen desaturation compared with healthy high-altitude dwellers. These alterations of nocturnal breathing and

Conclusions

We found that SDB and nocturnal oxygen desaturation are more severe in high-altitude dwellers with CMS than in healthy high-altitude dwellers. Most importantly, alterations in nocturnal breathing and oxygenation were associated with systemic and pulmonary vascular dysfunction. In the presence of a PFO, SDB and cardiovascular alterations were even more pronounced. This suggests, by analogy to recent observations in patients with sleep apnea syndrome at low altitude,55, 56 that PFO closure may

Acknowledgments

Author contributions: U. S. is the guarantor of the content of the manuscript, including the data and analysis. E. R. was involved in the clinical examinations, study design, data analysis and interpretation, and wrote a first draft of the paper. S. F. R., L. P., R. B., D. A., R. S., C. Salinas, M. V., Y. A., and A. L. contributed substantially to the clinical examinations, data analysis and interpretation, and the writing of the manuscript. C. R. was involved in recruiting patients and control

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It is well recognised that CMS associates with pulmonary vascular dysfunction [2], with emerging evidence indicating that the systemic circulation may be equally compromised, further compounding disease risk and premature mortality. In support, more marked impairments in flow-mediated dilation (FMD) and elevations in vascular stiffness and carotid intima-media thickness (cIMT) have been observed in comparatively more hypoxemic CMS patients (CMS+) compared to healthy well-adapted highlander (CMS-) and lowlander (sea-level) controls [3–6]. Furthermore, to what extent dietary deficiency of antioxidant micronutrients due to inadequate consumption of fruit and vegetables (F + V) further compounds systemic OXNOS is equally unknown, despite preliminary evidence for lower circulating concentrations of ascorbate and α/β-carotene in CMS+ [3].
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: Drs Heinzer, Sartori, and Scherrer contributed equally to this manuscript.

: FUNDING/SUPPORT: This work was supported by grants from the Swiss National Science Foundation and the Placide Nicod Foundation.

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Original Research: Sleep DisordersSleep-Disordered Breathing and Vascular Function in Patients With Chronic Mountain Sickness and Healthy High-Altitude Dwellers

Background

Methods

Results

Conclusions

Trial Registry

Section snippets

Materials and Methods

Results

Discussion

Conclusions

Acknowledgments

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Original Research: Sleep Disorders
Sleep-Disordered Breathing and Vascular Function in Patients With Chronic Mountain Sickness and Healthy High-Altitude Dwellers