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  • 1.
    Ljunggren, Mirjam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Sleep-disordered breathing in women: Associations with cardiovascular disease and the significance of sleep apnea during REM sleep2019Doctoral 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.

    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 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
    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
    Show others...
    (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
  • 2.
    Ljunggren, Mirjam
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Theorell-Haglöw, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Michaelsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Does sleep disordered breathing in women promote heart failure?: A population based cohort study2014In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 23, p. 119-119Article in journal (Other academic)
  • 3.
    Ljunggren, Mirjam
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Theorell-Haglöw, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Increased risk of heart failure in women with symptoms of sleep-disordered breathing2016In: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 17, p. 32-37Article in journal (Refereed)
    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.

  • 4.
    Ljunggren, Mirjam
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Theorell-Haglöw, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Association between obstructive sleep apnea and elevated levels of type B natriuretic peptide in a community-based sample of women2012In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 35, no 11, p. 1521-1527Article in journal (Refereed)
    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.

  • 5.
    Ljunggren, Mirjam
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Franklin, Karl A.
    Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Sweden.
    Öhagen, Patrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Theorell-Haglöw, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Gynecological endocrinology.
    Obstructive sleep apnea during rapid eye movement sleep is associated with early signs of atherosclerosis in women2018In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 41, no 7, article id zsy099Article in journal (Refereed)
    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.

  • 6.
    Palm, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Midgren, Bengt
    Lund Univ, Dept Clin Sci, Div Resp Med & Allergol, Lund, Sweden.
    Theorell-Haglöw, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Ekström, Magnus
    Lund Univ, Dept Clin Sci, Div Resp Med & Allergol, Lund, Sweden.
    Ljunggren, Mirjam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Factors influencing adherence to continuous positive airway pressure treatment in obstructive sleep apnea and mortality associated with treatment failure - a national registry-based cohort study2018In: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 51, p. 85-91, article id S1389-9457(18)30401-5Article in journal (Refereed)
    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.

  • 7.
    Theorell-Haglöw, Jenny
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Ljunggren, Mirjam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Franklin, K. A.
    Umea Univ, Umea, Sweden.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    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 study2017In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 40, p. A397-A398Article in journal (Other academic)
1 - 7 of 7
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