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Ljunggren, Mirjam
Publications (7 of 7) Show all publications
Ljunggren, M. (2019). Sleep-disordered breathing in women: Associations with cardiovascular disease and the significance of sleep apnea during REM sleep. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
Open this publication in new window or tab >>Sleep-disordered breathing in women: Associations with cardiovascular disease and the significance of sleep apnea during REM sleep
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
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
Obstructive sleep apnea, REM sleep, cardiovascular disease, heart failure
National Category
Respiratory Medicine and Allergy
Research subject
Lung Medicine
Identifiers
urn:nbn:se:uu:diva-381416 (URN)978-91-513-0640-7 (ISBN)
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: 2019-06-18
Palm, A., Midgren, B., Theorell-Haglöw, J., Ekström, M., Ljunggren, M., Janson, C. & Lindberg, E. (2018). Factors influencing adherence to continuous positive airway pressure treatment in obstructive sleep apnea and mortality associated with treatment failure - a national registry-based cohort study. Sleep Medicine, 51, 85-91, Article ID S1389-9457(18)30401-5.
Open this publication in new window or tab >>Factors influencing adherence to continuous positive airway pressure treatment in obstructive sleep apnea and mortality associated with treatment failure - a national registry-based cohort study
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2018 (English)In: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 51, p. 85-91, article id S1389-9457(18)30401-5Article in journal (Refereed) Published
Abstract [en]

Objectives: Adherence to continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) is crucial. Our aim was to identify protective and risk factors against the discontinuation of CPAP treatment in patients with OSA and to estimate the mortality risk in those who were non-adherent to CPAP therapy.

Methods: This was a registry-based cohort study from 37 centers across Sweden with OSA patients on CPAP in the Swedevox Swedish national registry between July 2010 and March 2017.

Results: In 16,425 patients (70.8% men) with complete follow-up data after 1.2 ± 0.8 years the adjusted relative risk ratio (aRRR) for the discontinuation of CPAP was 0.57 (95% confidence interval (CI) 0.50–0.65) for use of humidifier, 0.87 (95% CI 0.82–0.92) for increasing age per 10 years, 0.80 (95% CI 0.77–0.83) for increasing apnea hypopnea index (AHI) per 5 units/hour, and 0.96 (95% CI 0.95–0.97) per increased unit on the Epworth Sleepiness Scale (ESS). Increasing BMI was associated with increased adherence up to BMI 35. Women and patients with hypertension ran an increased risk of discontinuing CPAP treatment, aRRR 1.28 (95% CI 1.12–1.46) and 1.24 (95% CI 1.12–1.42) respectively. The adjusted hazard ratio (HR) for mortality was 1.74 (95% CI 1.32–2.28) among those who did not adhere to CPAP (median follow-up period 2.4 years after the one year adherence evaluation).

Conclusion: Use of humidifier is associated with greater adherence to CPAP treatment. Other factors predicting adherence are increasing age, more severe OSA and overweight up to BMI 35, whereas female gender and coexisting hypertension are risk factors for discontinuation of CPAP. Failure to adhere to CPAP is associated with increased mortality.

Keywords
Adherence, BMI, Continuous positive airway pressure (CPAP), Gender, Humidifier, Obstructive sleep apnea (OSA)
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-361337 (URN)10.1016/j.sleep.2018.07.007 (DOI)000447778200013 ()30103074 (PubMedID)
Funder
Swedish Association of Local Authorities and Regions
Available from: 2018-09-23 Created: 2018-09-23 Last updated: 2019-01-08Bibliographically approved
Ljunggren, M., Lindberg, E., Franklin, K. A., Öhagen, P., Larsson, M., Theorell-Haglöw, J. & Naessén, T. (2018). Obstructive sleep apnea during rapid eye movement sleep is associated with early signs of atherosclerosis in women. Sleep, 41(7), Article ID zsy099.
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
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2018 (English)In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 41, no 7, article id zsy099Article 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.

Keywords
obstructive sleep apnea, cardiovascular morbidity, rapid eye movement-related sleep apnea, carotid artery intima thickness, atherosclerosis
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-364687 (URN)10.1093/sleep/zsy099 (DOI)000439187200018 ()29762755 (PubMedID)
Funder
Swedish Heart Lung Foundation, 19990029Swedish Heart Lung Foundation, 20100494
Available from: 2018-10-31 Created: 2018-10-31 Last updated: 2019-07-03Bibliographically approved
Theorell-Haglöw, J., Ljunggren, M., Franklin, K. A. & Lindberg, E. (2017). Young women with short sleep duration and insomnia run a high risk of developing hypertension and diabetes mellitus: A 10-year follow-up of the population-based SHE study. Paper presented at 31st Annual Meeting of the Associated-Professional-Sleep-Societies (APSS), JUN 03-07, 2017, Boston, MA. Sleep, 40, A397-A398
Open this publication in new window or tab >>Young women with short sleep duration and insomnia run a high risk of developing hypertension and diabetes mellitus: A 10-year follow-up of the population-based SHE study
2017 (English)In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 40, p. A397-A398Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Oxford University Press, 2017
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-377543 (URN)10.1093/sleepj/zsx050.1068 (DOI)000433175001288 ()
Conference
31st Annual Meeting of the Associated-Professional-Sleep-Societies (APSS), JUN 03-07, 2017, Boston, MA
Funder
Swedish Heart Lung Foundation
Available from: 2019-02-21 Created: 2019-02-21 Last updated: 2019-02-21Bibliographically approved
Ljunggren, M., Byberg, L., Theorell-Haglöw, J., Lindahl, B., Michaëlsson, K. & Lindberg, E. (2016). Increased risk of heart failure in women with symptoms of sleep-disordered breathing. Sleep Medicine, 17, 32-37
Open this publication in new window or tab >>Increased risk of heart failure in women with symptoms of sleep-disordered breathing
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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
Ljunggren, M., Byberg, L., Theorell-Haglöw, J., Lindahl, B., Michaelsson, K. & Lindberg, E. (2014). Does sleep disordered breathing in women promote heart failure?: A population based cohort study. Paper presented at 22nd Congress of the European-Sleep-Research-Society, SEP 16-20, 2014, Tallinn, ESTONIA. Journal of Sleep Research, 23, 119-119
Open this publication in new window or tab >>Does sleep disordered breathing in women promote heart failure?: A population based cohort study
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2014 (English)In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 23, p. 119-119Article in journal, Meeting abstract (Other academic) Published
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-249086 (URN)000349960600305 ()
Conference
22nd Congress of the European-Sleep-Research-Society, SEP 16-20, 2014, Tallinn, ESTONIA
Available from: 2015-04-10 Created: 2015-04-10 Last updated: 2018-08-24Bibliographically approved
Ljunggren, M., Lindahl, B., Theorell-Haglöw, J. & Lindberg, E. (2012). Association between obstructive sleep apnea and elevated levels of type B natriuretic peptide in a community-based sample of women. Sleep, 35(11), 1521-1527
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
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