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] (]]]]) ]]]–]]]
Available online at www.sciencedirect.com
www.elsevier.com/locate/semperi
Sleep-disordered breathing and future cardiovascular disease risk Mary Ashley Cain, MDa, Jason Ricciuti, MDb, and Judette M. Louis, MD, MPHa,n a
Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of South Florida Morsani College of Medicine, 2 Tampa General Circle, Suite 6055, Tampa, FL 33609 b Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Women’s Hospital/University of Pittsburgh Medical Center, Pittsburgh, PA
article info
abstra ct
Keywords:
Sleep-disordered breathing occurs in 0.6–15% of reproductive age women. This condition is
sleep disorderd breathing
associated with an increased lifetime risk of cardiovascular disease, cardiovascular
preeclampsia
mortality, and all-cause mortality. A substantial body of evidence demonstrated increased
sleep apnea
perinatal morbidity among pregnancies affected by SDB including gestational diabetes,
obesity
gestational hypertension, and preeclampsia. These same conditions are predictive of later cardiovascular disease. Treatment of SDB has been demonstrated to decrease future cardiovascular events and mortality. Screening at-risk individuals in the perinatal period can identify women with SDB, who can benefit from treatment. Continuous positive airway pressure and lifestyle interventions can decrease subsequent adverse cardiovascular health outcomes. & 2015 Elsevier Inc. All rights reserved.
Introduction Sleep-disordered breathing (SDB) is a group of disorders characterized by abnormalities in ventilation and respiration. The spectrum ranges from snoring, which is considered mild, to the most severe form, obstructive sleep apnea (OSA).1 Obstructive sleep apnea involves repetitive partial or complete pharyngeal collapse while sleeping, resulting in either apnea or hypopnea.2 Repetitive nocturnal hypoxic events result in arousal from sleep, sleep fragmentation, and excessive daytime sleepiness.2,3 These events lead to a cascade of physiological responses that result in increased cardiovascular morbidity including stroke, diabetes, hypertension, and myocardial infarction.2,3
n
Corresponding author. E-mail address: [email protected] (J.M. Louis).
http://dx.doi.org/10.1053/j.semperi.2015.05.010 0146-0005/& 2015 Elsevier Inc. All rights reserved.
Despite the recognized morbidity and mortality associated with the disease, OSA remains underdiagnosed particularly in pregnancy. In this article, we will review the evidence for OSA associated morbidity, the pregnancy correlates of cardiovascular disease, and discuss the theoretical framework for future cardiovascular disease among women with pregnancy affected by sleep-disordered breathing.
Epidemiology and risk factors Sleep disorders are prevalent with approximately 40 million adults in the United States suffering from a sleep disorder. Of those 40 million adults, 18 million suffer from OSA.4 Obstructive sleep apnea occurs in 0.6–15% of reproductive aged
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women5,6 and an estimated 93% of these women remain undiagnosed.5,6 Risks factors for sleep-disordered breathing are well established and include male gender, obesity, older age, African– American race, and craniofacial abnormalities.4,7 The prevalence increases with elevated body mass index, neck circumference, and waist to hip ratio.6 Racial differences in craniofacial anatomy may predispose certain populations to the disorder such as Asians and African–Americans.2,8 Obesity remains a dominant risk factor. Even modest weight gain increases the risk of OSA.5,9 A longitudinal weight gain of 10% is associated with a 6-fold increase in the development of moderate or severe OSA.10 This effect is relevant to pregnancy as many women gain significantly more than 10% of body weight in that period. Studies of reproductive age women and pregnant women indicate that similar risk factors predict occurrence among pregnant women.11
Screening and diagnosis Symptoms of obstructive sleep apnea include excessive snoring, daytime fatigue, and non-restorative sleep.2,12 Women are more likely to report depression and anxiety as symptoms of sleep-disordered breathing. Further, they are often diagnosed with asthma and mood disorders prior to a diagnosis of OSA.13,14 It is uncertain if this relationship was due to a difference in the clinical symptoms of OSA in women or a gender bias in which OSA was not considered earlier during clinical management. In pregnancy, recognition of SDB is particularly difficult as symptoms of SDB overlap with symptoms of physiological changes pregnancy. Identifying SDB is further complicated by the lack of effective screening tools. Validated questionnaires used in the general population such as the Epworth Sleepiness Scale or the Berlin Questionnaire have not been demonstrated to be useful in the obstetric population. The reported sensitivities and specificities are 36–39% and 68–77% respectively.15–18 Polysomnography (PSG), an overnight in-laboratory sleep study is the gold standard for diagnosing OSA. This testing poses a challenge for reproductive age women who may have other children at home or work related responsibilities. Although widespread portable in-home polysomnography is widely accepted, these methods for OSA detection may underestimate the severity of SDB and are not yet validated for clinical use among pregnant women.19–21 All of these challenges contribute to the under-recognition of SDB among pregnant women.
SDB worsens in pregnancy Women with known sleep-disordered breathing prior to pregnancy typically experience a worsening of disease during pregnancy.11 Of 105 pregnant women enrolled in a prospective study of OSA risk factors, the rate of PSG diagnosed OSA increased from 10.5% in the first trimester to 26.7% in the third trimester.11 Further, smaller prospective studies of sleep-disordered breathing during gestation demonstrated
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spontaneous postpartum improvement.22,23 Reid et al. studied healthy women over the course of pregnancy with sleep questionnaires and polysomnography. They noted an increase in sleep-disordered breathing among women with gestational hypertension when compared to controls.24 On follow-up at 1–2 years postpartum, respiratory disturbance index improved among women with gestational hypertension to the level of controls.22 These improvements persisted despite a significantly greater body mass index among women with a history of gestational hypertension. These findings underscore the role of physiological changes in pregnancy on the development of SDB.
Comorbid conditions Both men and women with OSA suffer from increased rates of comorbid conditions including diabetes mellitus, hypertension, and cardiovascular disease.2,6 This increase in morbidity may be due in part to risk factors such as obesity. The association is apparent among pregnant women too. A recent systemic review by Ding et al. highlighted many comorbidities of sleep-disordered breathing found during pregnancy. Based on the pooled results of 12 studies, they found a significant association between gestational diabetes mellitus [(OR ¼ 1.78; 95% CI: 1.29–2.46; P o 0.001] and pregnancy-related hypertension [(OR ¼ 2.38; 95% CI: 1.63– 3.47; P o 0.001)] and moderate-to-severe SDB.25
Sleep-disordered breathing and pregnancy-related morbidity The cardiovascular implications of untreated OSA are substantial and complex. Several large, population-based studies provide clear evidence for an independent association between OSA and cardiovascular disease, particularly hypertension.10,26–29 These associations persist after controlling for confounding factors such BMI, age, or gender. The associations also appear to have a dose–response indicating the highest risk among patients with severe OSA.10,30 Accumulating evidence now indicates an increased risk of gestational hypertension and preeclampsia in pregnancies affected by OSA. This data, obtained through retrospective, cross-sectional, and prospective cohort studies consistently report a 2fold increased risk of hypertension.31–33 A recent retrospective cohort study of 1700 pregnant women demonstrated that women who snored during pregnancy, a symptom often used as a proxy for OSA, were more likely to develop gestational hypertension [OR ¼ 2.1 (95% CI: 1.1–3.6)] and preeclampsia [OR ¼ 1.7 (95% CI: 1.1–2.6)] even after controlling for known risk factors for hypertensive disorders.14 This finding is not surprising as OSA and preeclampsia have common mechanistic pathways that include inflammation, insulin resistance, endothelial injury, and oxidative stress.34–38 A recent study examined the impact of OSA in pregnancy on severe morbidities; conditions used to proximate causes of maternal mortality. In a review of data from the United States Nationwide Inpatient Sample, a national sample of delivery related hospital discharges; OSA was associated with in-
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hospital death, cardiomyopathy, and stroke. These relationships persisted after adjusting for obesity.39 This preliminary evidence demonstrates a persistence of the associations between OSA and severe morbidities seen in the general population among pregnant populations. The data on adverse neonatal outcomes is not consistent. Prior reports associate preterm delivery and growth restriction with sleep-disordered breathing.14,40 Some of these associations were secondary to preeclampsia and no studies delineate a clear relationship independent of preeclampsia. Based on current evidence we are unable to infer an independent relationship between preterm birth, stillbirth, or growth restriction and SDB.
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women with polysomnogram-confirmed OSA by Chen et al.,40 OSA was associated with gestational diabetes [OR ¼ 1.63 (95% CI: 1.07–2.48)]. A US population-based cohort with a similar magnitude of effect confirmed this finding.39 Both studies underreported on obesity. A more recent prospective study of pregnant women with prepregnancy BMI under 35 kg/m2 and no medical comorbidities failed to find an association between OSA and gestational diabetes.47 These conflicted findings underscore the importance of adjusting for obesity when attempting to ascertain the role of OSA in pregestational and gestational diabetes. Adiposity and central obesity are significant risk factors for both diabetes and OSA. Independently these factors may exert an effect on glucose metabolism.48,49
Obstructive sleep apnea and glucose intolerance in pregnancy
Pathogenic mechanisms
A clear and consistent body of literature demonstrates an association between diabetes and OSA in the general population.41 Untreated OSA is associated with the increased likelihood of subsequently developing diabetes. Further, even after controlling for obesity worsening OSA worsens leads to increasing insulin resistance. Studies addressing the effect of CPAP treatment in OSA on insulin resistance are mixed with some studies demonstrating a beneficial effect and others failing to normalize glucose.42–46 Recent studies of SDB among pregnant women investigated the relationship between OSA and insulin resistance or diabetes among pregnant women. In a population-based study of 791
Possible pathogenic mechanisms for increased morbidity in sleep-disordered breathing include an increase in oxidative stress, sympathetic activation, and inflammation due to chronic hypoxemic episodes and sleep fragmentation.50 This chronic stress and inflammation leads to increased insulin resistance, elevated blood pressures, and cardiovascular disease.50 While the majority of research on these pathogenic mechanisms includes non-pregnant individuals, similar mechanisms may lead to increased morbidity noted among pregnant individuals with sleep-disordered breathing. These mechanisms overlap with the theorized mechanisms in pregnancy-related disease states such as gestational diabetes and preeclampsia. (Fig.)
Fig. – Mechanisms for the adverse effects of OSA and the implications for future health.
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Treatment of obstructive sleep apnea Continuous positive airway pressure (CPAP) is the treatment of choice for mild, moderate, and severe OSA.51 More than 15 randomized clinical trials demonstrated the effectiveness of CPAP.52 In observational trials, treatment attenuates the risks of hypertension and cardiovascular morbidities associated with OSA. One study demonstrated a 64% risk reduction among OSA patients treated with CPAP versus those without treatment independent of age or preexisting risk factors.53 The number needed to treat to prevent one cardiovascular event in a 10-year period was 3.5.53 Meta-analyses demonstrate a reduction in motor vehicle crashes and acute decreases in blood pressure among patients with OSA, who are treated with CPAP.54,55 Limited data directing the treatment of OSA during pregnancy exists. Small studies used short-term intermediary outcomes such as maternal blood pressure. The studies were insufficiently powered to detect an impact of treatment. In a 2007 randomized controlled trial, CPAP treatment in pregnant women with hypertension and chronic snoring led to decreased blood pressure compared to patients treated with placebo.56 However, the effect size was small, and the total numbers of study subjects were limited to 16 and insufficient to detect a difference between the treatment groups.
OSA and future health Obstructive sleep apnea is associated with a subsequent risk of development of cardiovascular disease, stroke, and hypertension. Also increased are associated work related injuries and motor vehicle accidents.12 A cross-sectional analysis of data from the Sleep Heart Health Study, a prospective study of cardiovascular disease and sleep-disordered breathing, noted a positive association between increasing apnea–hypopnea index and self-reported hypertension and cardiovascular disease including stroke and myocardial infarction. During the average 8.7-year follow-up period, untreated OSA was associated with an increased risk of stroke. Among female participants, a baseline AHI Z 30 was associated with a significantly increased risk of hypertension [OR ¼ 2.71 (95% CI: 1.24–5.93)]. Among the cohort of 2470 participants, increasing apnea–hypopnea index was also associated with subsequent development of hypertension. However, these findings did not remain statistically significant once adjusted for body mass index.57 The Wisconsin Sleep Cohort noted a dose–response and linear relationship between OSA and development of HTN.29 Severe OSA demonstrated the greatest association with an OR of 2.89 (95% CI: 1.4–5.6). Among those patients with drug-resistant hypertension, 83% suffered from an apnea/hypopnea index of Z10.29 Morbidity is not limited to cardiovascular disease. All-cause mortality and motor vehicle accidents are also increased [OR ¼ 6.3 (95% CI: 2.4–16.2)] among patients with an apnea–hypopnea index greater than 10.58 While treatment with CPAP has been demonstrated be beneficial in the reduction of morbidity and mortality, the most important intervention may be weight loss.51 Weight loss can improve or cure comorbid conditions such as
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hypertension, diabetes, and sleep apnea, resulting in an improved cardiovascular disease risk profile.59
Screening for future health Given the clear and consistent picture of sleep-disordered breathing and future cardiovascular disease risk, identifying women at risk for the development of sleep-disordered breathing or suffering from sleep-disordered breathing can decrease subsequent morbidity. Treatment through the use of CPAP and weight loss may lead to decreased risk of cardiovascular disease and mortality later in life. The American Academy of Sleep Medicine recommends routine evaluation of snoring, sleep quality, and body habitus at health maintenance visits. If risks factors are identified, then more thorough evaluation should be completed.60 This questioning can be applied to routine prenatal and postpartum visits. The American Academy of Sleep Medicine identifies individuals suffering from obesity (BMI 4 30 kg/m2), a history of heart failure, arrhythmias, drug-resistant hypertension, or type two diabetes as high risk for OSA and therefore should undergo screening.51 Women with these risk factors in the perinatal period warrant screening as well. Both hypertensive disorders of pregnancy and sleepdisordered breathing increase a woman’s risk of cardiovascular disease later in life. There currently is a paucity of research on the future health of women with preexisting SDB that worsens during pregnancy or SDB that occurs only in pregnancy. Based on the association between SDB and hypertensive disorders of pregnancy and the association between hypertensive disorders of pregnancy and future cardiovascular disease, researchers could hypothesize that worsening SDB in pregnancy may increase the risk of cardiovascular disease later in life. Due to the association between hypertensive disorders of pregnancy and OSA these women also warrant screening for and education about OSA. By identifying women at risk for OSA or suffering from the disease in the perinatal period, treatment with CPAP and ideally, weight loss can decrease the risk of future cardiovascular disease.
re fe r en ces
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Available online at www.sciencedirect.com
www.elsevier.com/locate/semperi
Sleep-disordered breathing and future cardiovascular disease risk Mary Ashley Cain, MDa, Jason Ricciuti, MDb, and Judette M. Louis, MD, MPHa,n a
Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of South Florida Morsani College of Medicine, 2 Tampa General Circle, Suite 6055, Tampa, FL 33609 b Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Women’s Hospital/University of Pittsburgh Medical Center, Pittsburgh, PA
article info
abstra ct
Keywords:
Sleep-disordered breathing occurs in 0.6–15% of reproductive age women. This condition is
sleep disorderd breathing
associated with an increased lifetime risk of cardiovascular disease, cardiovascular
preeclampsia
mortality, and all-cause mortality. A substantial body of evidence demonstrated increased
sleep apnea
perinatal morbidity among pregnancies affected by SDB including gestational diabetes,
obesity
gestational hypertension, and preeclampsia. These same conditions are predictive of later cardiovascular disease. Treatment of SDB has been demonstrated to decrease future cardiovascular events and mortality. Screening at-risk individuals in the perinatal period can identify women with SDB, who can benefit from treatment. Continuous positive airway pressure and lifestyle interventions can decrease subsequent adverse cardiovascular health outcomes. & 2015 Elsevier Inc. All rights reserved.
Introduction Sleep-disordered breathing (SDB) is a group of disorders characterized by abnormalities in ventilation and respiration. The spectrum ranges from snoring, which is considered mild, to the most severe form, obstructive sleep apnea (OSA).1 Obstructive sleep apnea involves repetitive partial or complete pharyngeal collapse while sleeping, resulting in either apnea or hypopnea.2 Repetitive nocturnal hypoxic events result in arousal from sleep, sleep fragmentation, and excessive daytime sleepiness.2,3 These events lead to a cascade of physiological responses that result in increased cardiovascular morbidity including stroke, diabetes, hypertension, and myocardial infarction.2,3
n
Corresponding author. E-mail address: [email protected] (J.M. Louis).
http://dx.doi.org/10.1053/j.semperi.2015.05.010 0146-0005/& 2015 Elsevier Inc. All rights reserved.
Despite the recognized morbidity and mortality associated with the disease, OSA remains underdiagnosed particularly in pregnancy. In this article, we will review the evidence for OSA associated morbidity, the pregnancy correlates of cardiovascular disease, and discuss the theoretical framework for future cardiovascular disease among women with pregnancy affected by sleep-disordered breathing.
Epidemiology and risk factors Sleep disorders are prevalent with approximately 40 million adults in the United States suffering from a sleep disorder. Of those 40 million adults, 18 million suffer from OSA.4 Obstructive sleep apnea occurs in 0.6–15% of reproductive aged
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women5,6 and an estimated 93% of these women remain undiagnosed.5,6 Risks factors for sleep-disordered breathing are well established and include male gender, obesity, older age, African– American race, and craniofacial abnormalities.4,7 The prevalence increases with elevated body mass index, neck circumference, and waist to hip ratio.6 Racial differences in craniofacial anatomy may predispose certain populations to the disorder such as Asians and African–Americans.2,8 Obesity remains a dominant risk factor. Even modest weight gain increases the risk of OSA.5,9 A longitudinal weight gain of 10% is associated with a 6-fold increase in the development of moderate or severe OSA.10 This effect is relevant to pregnancy as many women gain significantly more than 10% of body weight in that period. Studies of reproductive age women and pregnant women indicate that similar risk factors predict occurrence among pregnant women.11
Screening and diagnosis Symptoms of obstructive sleep apnea include excessive snoring, daytime fatigue, and non-restorative sleep.2,12 Women are more likely to report depression and anxiety as symptoms of sleep-disordered breathing. Further, they are often diagnosed with asthma and mood disorders prior to a diagnosis of OSA.13,14 It is uncertain if this relationship was due to a difference in the clinical symptoms of OSA in women or a gender bias in which OSA was not considered earlier during clinical management. In pregnancy, recognition of SDB is particularly difficult as symptoms of SDB overlap with symptoms of physiological changes pregnancy. Identifying SDB is further complicated by the lack of effective screening tools. Validated questionnaires used in the general population such as the Epworth Sleepiness Scale or the Berlin Questionnaire have not been demonstrated to be useful in the obstetric population. The reported sensitivities and specificities are 36–39% and 68–77% respectively.15–18 Polysomnography (PSG), an overnight in-laboratory sleep study is the gold standard for diagnosing OSA. This testing poses a challenge for reproductive age women who may have other children at home or work related responsibilities. Although widespread portable in-home polysomnography is widely accepted, these methods for OSA detection may underestimate the severity of SDB and are not yet validated for clinical use among pregnant women.19–21 All of these challenges contribute to the under-recognition of SDB among pregnant women.
SDB worsens in pregnancy Women with known sleep-disordered breathing prior to pregnancy typically experience a worsening of disease during pregnancy.11 Of 105 pregnant women enrolled in a prospective study of OSA risk factors, the rate of PSG diagnosed OSA increased from 10.5% in the first trimester to 26.7% in the third trimester.11 Further, smaller prospective studies of sleep-disordered breathing during gestation demonstrated
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spontaneous postpartum improvement.22,23 Reid et al. studied healthy women over the course of pregnancy with sleep questionnaires and polysomnography. They noted an increase in sleep-disordered breathing among women with gestational hypertension when compared to controls.24 On follow-up at 1–2 years postpartum, respiratory disturbance index improved among women with gestational hypertension to the level of controls.22 These improvements persisted despite a significantly greater body mass index among women with a history of gestational hypertension. These findings underscore the role of physiological changes in pregnancy on the development of SDB.
Comorbid conditions Both men and women with OSA suffer from increased rates of comorbid conditions including diabetes mellitus, hypertension, and cardiovascular disease.2,6 This increase in morbidity may be due in part to risk factors such as obesity. The association is apparent among pregnant women too. A recent systemic review by Ding et al. highlighted many comorbidities of sleep-disordered breathing found during pregnancy. Based on the pooled results of 12 studies, they found a significant association between gestational diabetes mellitus [(OR ¼ 1.78; 95% CI: 1.29–2.46; P o 0.001] and pregnancy-related hypertension [(OR ¼ 2.38; 95% CI: 1.63– 3.47; P o 0.001)] and moderate-to-severe SDB.25
Sleep-disordered breathing and pregnancy-related morbidity The cardiovascular implications of untreated OSA are substantial and complex. Several large, population-based studies provide clear evidence for an independent association between OSA and cardiovascular disease, particularly hypertension.10,26–29 These associations persist after controlling for confounding factors such BMI, age, or gender. The associations also appear to have a dose–response indicating the highest risk among patients with severe OSA.10,30 Accumulating evidence now indicates an increased risk of gestational hypertension and preeclampsia in pregnancies affected by OSA. This data, obtained through retrospective, cross-sectional, and prospective cohort studies consistently report a 2fold increased risk of hypertension.31–33 A recent retrospective cohort study of 1700 pregnant women demonstrated that women who snored during pregnancy, a symptom often used as a proxy for OSA, were more likely to develop gestational hypertension [OR ¼ 2.1 (95% CI: 1.1–3.6)] and preeclampsia [OR ¼ 1.7 (95% CI: 1.1–2.6)] even after controlling for known risk factors for hypertensive disorders.14 This finding is not surprising as OSA and preeclampsia have common mechanistic pathways that include inflammation, insulin resistance, endothelial injury, and oxidative stress.34–38 A recent study examined the impact of OSA in pregnancy on severe morbidities; conditions used to proximate causes of maternal mortality. In a review of data from the United States Nationwide Inpatient Sample, a national sample of delivery related hospital discharges; OSA was associated with in-
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hospital death, cardiomyopathy, and stroke. These relationships persisted after adjusting for obesity.39 This preliminary evidence demonstrates a persistence of the associations between OSA and severe morbidities seen in the general population among pregnant populations. The data on adverse neonatal outcomes is not consistent. Prior reports associate preterm delivery and growth restriction with sleep-disordered breathing.14,40 Some of these associations were secondary to preeclampsia and no studies delineate a clear relationship independent of preeclampsia. Based on current evidence we are unable to infer an independent relationship between preterm birth, stillbirth, or growth restriction and SDB.
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women with polysomnogram-confirmed OSA by Chen et al.,40 OSA was associated with gestational diabetes [OR ¼ 1.63 (95% CI: 1.07–2.48)]. A US population-based cohort with a similar magnitude of effect confirmed this finding.39 Both studies underreported on obesity. A more recent prospective study of pregnant women with prepregnancy BMI under 35 kg/m2 and no medical comorbidities failed to find an association between OSA and gestational diabetes.47 These conflicted findings underscore the importance of adjusting for obesity when attempting to ascertain the role of OSA in pregestational and gestational diabetes. Adiposity and central obesity are significant risk factors for both diabetes and OSA. Independently these factors may exert an effect on glucose metabolism.48,49
Obstructive sleep apnea and glucose intolerance in pregnancy
Pathogenic mechanisms
A clear and consistent body of literature demonstrates an association between diabetes and OSA in the general population.41 Untreated OSA is associated with the increased likelihood of subsequently developing diabetes. Further, even after controlling for obesity worsening OSA worsens leads to increasing insulin resistance. Studies addressing the effect of CPAP treatment in OSA on insulin resistance are mixed with some studies demonstrating a beneficial effect and others failing to normalize glucose.42–46 Recent studies of SDB among pregnant women investigated the relationship between OSA and insulin resistance or diabetes among pregnant women. In a population-based study of 791
Possible pathogenic mechanisms for increased morbidity in sleep-disordered breathing include an increase in oxidative stress, sympathetic activation, and inflammation due to chronic hypoxemic episodes and sleep fragmentation.50 This chronic stress and inflammation leads to increased insulin resistance, elevated blood pressures, and cardiovascular disease.50 While the majority of research on these pathogenic mechanisms includes non-pregnant individuals, similar mechanisms may lead to increased morbidity noted among pregnant individuals with sleep-disordered breathing. These mechanisms overlap with the theorized mechanisms in pregnancy-related disease states such as gestational diabetes and preeclampsia. (Fig.)
Fig. – Mechanisms for the adverse effects of OSA and the implications for future health.
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Treatment of obstructive sleep apnea Continuous positive airway pressure (CPAP) is the treatment of choice for mild, moderate, and severe OSA.51 More than 15 randomized clinical trials demonstrated the effectiveness of CPAP.52 In observational trials, treatment attenuates the risks of hypertension and cardiovascular morbidities associated with OSA. One study demonstrated a 64% risk reduction among OSA patients treated with CPAP versus those without treatment independent of age or preexisting risk factors.53 The number needed to treat to prevent one cardiovascular event in a 10-year period was 3.5.53 Meta-analyses demonstrate a reduction in motor vehicle crashes and acute decreases in blood pressure among patients with OSA, who are treated with CPAP.54,55 Limited data directing the treatment of OSA during pregnancy exists. Small studies used short-term intermediary outcomes such as maternal blood pressure. The studies were insufficiently powered to detect an impact of treatment. In a 2007 randomized controlled trial, CPAP treatment in pregnant women with hypertension and chronic snoring led to decreased blood pressure compared to patients treated with placebo.56 However, the effect size was small, and the total numbers of study subjects were limited to 16 and insufficient to detect a difference between the treatment groups.
OSA and future health Obstructive sleep apnea is associated with a subsequent risk of development of cardiovascular disease, stroke, and hypertension. Also increased are associated work related injuries and motor vehicle accidents.12 A cross-sectional analysis of data from the Sleep Heart Health Study, a prospective study of cardiovascular disease and sleep-disordered breathing, noted a positive association between increasing apnea–hypopnea index and self-reported hypertension and cardiovascular disease including stroke and myocardial infarction. During the average 8.7-year follow-up period, untreated OSA was associated with an increased risk of stroke. Among female participants, a baseline AHI Z 30 was associated with a significantly increased risk of hypertension [OR ¼ 2.71 (95% CI: 1.24–5.93)]. Among the cohort of 2470 participants, increasing apnea–hypopnea index was also associated with subsequent development of hypertension. However, these findings did not remain statistically significant once adjusted for body mass index.57 The Wisconsin Sleep Cohort noted a dose–response and linear relationship between OSA and development of HTN.29 Severe OSA demonstrated the greatest association with an OR of 2.89 (95% CI: 1.4–5.6). Among those patients with drug-resistant hypertension, 83% suffered from an apnea/hypopnea index of Z10.29 Morbidity is not limited to cardiovascular disease. All-cause mortality and motor vehicle accidents are also increased [OR ¼ 6.3 (95% CI: 2.4–16.2)] among patients with an apnea–hypopnea index greater than 10.58 While treatment with CPAP has been demonstrated be beneficial in the reduction of morbidity and mortality, the most important intervention may be weight loss.51 Weight loss can improve or cure comorbid conditions such as
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hypertension, diabetes, and sleep apnea, resulting in an improved cardiovascular disease risk profile.59
Screening for future health Given the clear and consistent picture of sleep-disordered breathing and future cardiovascular disease risk, identifying women at risk for the development of sleep-disordered breathing or suffering from sleep-disordered breathing can decrease subsequent morbidity. Treatment through the use of CPAP and weight loss may lead to decreased risk of cardiovascular disease and mortality later in life. The American Academy of Sleep Medicine recommends routine evaluation of snoring, sleep quality, and body habitus at health maintenance visits. If risks factors are identified, then more thorough evaluation should be completed.60 This questioning can be applied to routine prenatal and postpartum visits. The American Academy of Sleep Medicine identifies individuals suffering from obesity (BMI 4 30 kg/m2), a history of heart failure, arrhythmias, drug-resistant hypertension, or type two diabetes as high risk for OSA and therefore should undergo screening.51 Women with these risk factors in the perinatal period warrant screening as well. Both hypertensive disorders of pregnancy and sleepdisordered breathing increase a woman’s risk of cardiovascular disease later in life. There currently is a paucity of research on the future health of women with preexisting SDB that worsens during pregnancy or SDB that occurs only in pregnancy. Based on the association between SDB and hypertensive disorders of pregnancy and the association between hypertensive disorders of pregnancy and future cardiovascular disease, researchers could hypothesize that worsening SDB in pregnancy may increase the risk of cardiovascular disease later in life. Due to the association between hypertensive disorders of pregnancy and OSA these women also warrant screening for and education about OSA. By identifying women at risk for OSA or suffering from the disease in the perinatal period, treatment with CPAP and ideally, weight loss can decrease the risk of future cardiovascular disease.
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