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Sleep-disordered breathing in women: Associations with cardiovascular disease and the significance of sleep apnea during REM sleep
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Description
Abstract [en]

Background: Sleep-disordered breathing (SDB) is associated with an increased risk of cardiovascular disease, but it is unclear which elements of SDB that are most harmful to the cardiovascular system and whether the associations observed in men also apply to women.

Aim: To investigate associations between different aspects of SDB and cardiovascular disease in women

Methods and results: All four papers were based on participants in “Sleep and Health in Women” (SHE), a population-based cohort study of women.

Paper I is a cross-sectional study of 349 women with polysomnographic assessments of obstructive sleep apnea (OSA) and measurements of plasma BNP, clinically used as a marker of heart failure, in the morning. There was a dose-response relationship between the severity of OSA and levels of BNP.

In Paper II, with a study population of 5,990 women, questionnaire data on symptoms of obstructive sleep apnea were combined with register data from the Swedish National Patient Register regarding a diagnosis of heart failure (mean follow-up 11.4 years). Women with the combination of snoring and daytime sleepiness had a two-fold increase in the risk of incident heart failure after adjustment for confounding.

Paper III was based on 201 women without known cardiovascular disease, with a polysomnography at baseline, assessing OSA during REM sleep, and a carotid artery ultrasound with measurements of intima thickness at follow-up. Severe OSA during REM sleep was associated with a thicker carotid intima.

Paper IV comprised 253 women with polysomnographic data on severe OSA and severe OSA during REM sleep, as well as proteomic analyses of cardiac and inflammatory proteins. After adjustment for confounding and multiple testing, severe OSA during REM sleep was associated with decreased levels of Sirt2, LAP-TGF-β1 and Axin1, while there were no significant associations for OSA based on a whole night and protein levels.

Conclusions: Women with symptoms of OSA run an increased risk of developing heart failure and OSA is associated with increased levels of BNP. Severe OSA during REM sleep is associated with an early sign of atherosclerosis and reduced levels of proteins with anti-inflammatory effects linked to atherosclerosis and metabolic regulation.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. , p. 75
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1567
Keywords [en]
Obstructive sleep apnea, REM sleep, cardiovascular disease, heart failure
National Category
Respiratory Medicine and Allergy
Research subject
Lung Medicine
Identifiers
URN: urn:nbn:se:uu:diva-381416ISBN: 978-91-513-0640-7 (print)OAI: oai:DiVA.org:uu-381416DiVA, id: diva2:1303436
Public defence
2019-06-05, Enghoffsalen, Akademiska sjukhuset, Ing 50 bv, Uppsala, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2019-05-15 Created: 2019-04-09 Last updated: 2019-05-15
List of papers
1. Association between obstructive sleep apnea and elevated levels of type B natriuretic peptide in a community-based sample of women
Open this publication in new window or tab >>Association between obstructive sleep apnea and elevated levels of type B natriuretic peptide in a community-based sample of women
2012 (English)In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 35, no 11, p. 1521-1527Article in journal (Refereed) Published
Abstract [en]

Study Objectives:

Obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular disease. One contributory factor may be hemodynamic stress due to the negative intrathoracic pressure during each episode of apnea. Type B natriuretic peptide (BNP) is secreted by the cardiac ventricles in response to volume expansion and pressure load and the authors hypothesized that there would be an association between indices of OSA during the night and levels of BNP in the morning.

Setting:

Community-based in Uppsala, Sweden.

Participants:

There were 349 women who participated.

Measurements and Results:

Participants underwent full-night polysomnography and anthropometric measurements, and answered questionnaires about medical conditions and current medication. The morning after the polysomnography, blood samples were drawn for analysis of plasma BNP, C-reactive protein, creatinine, and hemoglobin. There was an increase in mean BNP as the severity of sleep apnea increased, increasing from a mean value of 8.5 ng/L among women with an apnea-hypopnea index (AHI) < 5 to 18.0 ng/L in women with an AHI = 30. Elevated BNP levels (= 20 ng/L) were found in 29.8% of the women, whereas 70.2% had normal levels. The odds ratio was 2.2 for elevated BNP levels for women with an AHI of 5-14.9 in relation to women with an AHI < 5, 3.1 for women with an AHI of 15-29.9, and 4.6 for women with an AHI = 30 after adjustment for age, body mass index, systolic blood pressure, antihypertensive drugs, and creatinine.

Conclusions:

There is a dose-response relationship in women between the severity of sleep apnea during the night and the levels of BNP in the morning.

Keywords
Community-based, Epidemiology, Heart failure, Polysomnography, Sleep apnea
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-184929 (URN)10.5665/sleep.2202 (DOI)000310578200013 ()
Available from: 2012-11-19 Created: 2012-11-15 Last updated: 2019-04-09Bibliographically approved
2. Increased risk of heart failure in women with symptoms of sleep-disordered breathing
Open this publication in new window or tab >>Increased risk of heart failure in women with symptoms of sleep-disordered breathing
Show others...
2016 (English)In: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 17, p. 32-37Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: An association between obstructive sleep apnea and the incidence of heart failure has been reported in men but not in women. The aim of this study was to investigate whether a combination of snoring and excessive daytime sleepiness, the two main symptoms of obstructive sleep apnea syndrome, was able to predict incident heart failure in a population-based sample of women.

METHODS: The population-based cohort study Sleep and Health in Women (SHE; n = 5990 women born between 1901 and 1980) was used, with baseline questionnaire data from April 2000 relating to snoring, excessive daytime sleepiness, and covariates. Using data retrieved from the Swedish National Patient Register and Cause of Death Register, the follow-up of incident heart failure continued until 31 December 2011.

RESULTS: Among women with both snoring and excessive daytime sleepiness at baseline, 5.3% developed heart failure during follow-up compared with 0.9% in the reference group with neither snoring nor excessive daytime sleepiness. After adjustment for age, waist circumference, smoking, alcohol, hypertension, diabetes, previous myocardial infarction, physical inactivity, depressive symptoms, menopausal status, and hormone replacement therapy, women with the combination of snoring and excessive daytime sleepiness had a twofold increase in the risk of incident heart failure (hazard ratio [HR] 2.2 95% confidence interval [CI] 1.1-4.4).

CONCLUSION: Symptoms of obstructive sleep apnea, that is, the combination of snoring and excessive daytime sleepiness, are associated with an increased risk of developing heart failure in women.

Keywords
Obstructive sleep apnea syndrome; Heart failure; Women; Snoring; Excessive daytime sleepiness
National Category
Medical and Health Sciences Neurology Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-277627 (URN)10.1016/j.sleep.2015.09.018 (DOI)000370897100007 ()26847971 (PubMedID)
Funder
Swedish Heart Lung Foundation, 19990029Swedish Heart Lung Foundation, 20100494
Available from: 2016-02-22 Created: 2016-02-22 Last updated: 2019-04-09Bibliographically approved
3. Obstructive sleep apnea during rapid eye movement sleep is associated with early signs of atherosclerosis in women.
Open this publication in new window or tab >>Obstructive sleep apnea during rapid eye movement sleep is associated with early signs of atherosclerosis in women.
Show others...
2018 (English)In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 41, no 7Article in journal (Refereed) Published
Abstract [en]

Study Objectives: Although obstructive sleep apnea (OSA) is associated with overall cardiovascular disease and mortality, the association with atherosclerotic cardiovascular disease is less clear, especially in women. Recently, it has been suggested that OSA during rapid eye movement (REM) sleep, associated with long apneas and deep desaturations, could have severe cardiometabolic consequences. The aim of this study was to investigate whether OSA during REM sleep is associated with early signs of atherosclerosis in a population-based sample of women.

Methods: In the community-based "Sleep and Health in Women" (SHE) cohort study, 400 women underwent polysomnography, anthropometric measurements, blood sampling, blood pressure measurement, and answered questionnaires. Ten years later, 201 of the original participants, free of known atherosclerotic disease at baseline and without continuous positive airway pressure treatment for OSA, underwent a high-frequency ultrasound of the common carotid artery to assess the individual thickness of the layers of the artery wall.

Results: Severe OSA during REM sleep (REM apnea-hypopnea index [AHI] ≥ 30) was associated with a thicker intima. This association was still significant after adjustment for age, body mass index, alcohol, and smoking, as well as for further adjustment for systolic blood pressure, low-density lipoprotein, C-reactive protein, and diabetes (β-coefficient, 0.008; p-value, 0.022). The association between a REM AHI of ≥30 and intima thickness was also seen in women with no or mild OSA and normal non-REM AHI.

Conclusions: In this study of a community-based sample of women, severe OSA during REM sleep was independently associated with early signs of atherosclerosis.

National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-364687 (URN)10.1093/sleep/zsy099 (DOI)29762755 (PubMedID)
Available from: 2018-10-31 Created: 2018-10-31 Last updated: 2019-04-09Bibliographically approved
4. Sleep apnea during REM sleep matters!: A proteomic approach to studying the impact of different measurements of sleep-disordered breathing
Open this publication in new window or tab >>Sleep apnea during REM sleep matters!: A proteomic approach to studying the impact of different measurements of sleep-disordered breathing
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(English)Manuscript (preprint) (Other academic)
National Category
Respiratory Medicine and Allergy
Research subject
Lung Medicine
Identifiers
urn:nbn:se:uu:diva-381411 (URN)
Available from: 2019-04-09 Created: 2019-04-09 Last updated: 2019-04-09

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