Curr Hypertens Rep (2014) 16:482 DOI 10.1007/s11906-014-0482-4
PATHOGENESIS OF HYPERTENSION (W ELLIOTT, SECTION EDITOR)
Obstructive Sleep Apnea and Hypertension: a Critical Review Vahid Mohsenin
Published online: 20 August 2014 # Springer Science+Business Media New York 2014
Abstract Obstructive sleep apnea (OSA) is a prevalent sleep disorder which is characterized by recurrent upper closure with oxygen desaturation and sleep disruption. OSA increases the risk of vascular disorders in the form of stroke, myocardial infarction, congestive heart failure, and hypertension. The mechanisms underlying the vascular disorders are several and include intermittent hypoxia with release of cytokines, angiogenic inhibitors, free radicals, and adhesion molecules. During apneas, arterial blood pressure gradually rises and surges abruptly after the termination of apnea. Two thirds of patients with OSA will ultimately have diurnal hypertension. This review discusses the literature supporting the significant role of OSA in hypertension and the effect of OSA treatment on blood pressure. Keywords Obstructive sleep apnea . Hypertension . Endothelial dysfunction . Angiogenic inhibitors
Introduction Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder that affects 15–24 % of the adults and is associated with increased morbidity and mortality [1]. OSA is characterized by recurrent upper airway obstruction during sleep. These episodes are terminated by arousals and are commonly associated with hypoxemia. A growing body of evidence shows that OSA syndrome is independently associated with significant cardiovascular morbidity and mortality, including This article is part of the Topical Collection on Pathogenesis of Hypertension V. Mohsenin (*) Section of Pulmonary, Critical Care and Sleep Medicine, Yale University, P.O. Box 208057, LLCI 106, 15 York Street, New Haven, CT 06510, USA e-mail: [email protected]
coronary artery disease, heart failure, and stroke [2–4]. The acute hemodynamic and autonomic perturbations that accompany obstructive apneas during sleep, with associated arousals and intermittent hypoxemia, can lead to sustained diurnal hypertension in susceptible individuals, independent of other known risk factors for hypertension [5–8].
Prevalence of Hypertension in OSA Cross-sectional Studies OSA and hypertension are common, and many individuals have both conditions. The prevalence of hypertension in OSA ranges from 30 to 70 % [9]. An estimated 30 % of hypertensive patients also have OSA, often undiagnosed [9, 10]. Three large cross-sectional studies were reported between 1997 and 2000. The first report was a cross-sectional analysis of Wisconsin Sleep Cohort where 1,060 employed women (n=452) and men (n=617) aged 30 to 60 years who had an overnight polysomnography and blood pressure measurement were included. The multiple logistic regression analysis, with inclusion of apnea-hypopnea index (AHI), age, body mass index (BMI), and an interaction term for BMI and AHI, indicated that each additional apneas or hypopneas per hour of sleep increased the risk of having hypertension by 3.7 %. The odds ratios and 95 % confidence intervals (CIs) for hypertension associated with AHI levels of 5, 15, and 30 for BMI of 30 kg/m2 were 1.21 (95 % CI 1.09–1.34), 1.75 (95 % CI 1.28–2.40), and 3.07 (95 % CI 1.65–1.74), respectively. The odds ratios were attenuated with increasing BMI but remained statistically significant. This study showed that sleep-disordered breathing was associated with an increased prevalence of hypertension in employed middle-aged adults. It further demonstrated that the risk of hypertension was also present with a milder form of sleep-disordered breathing. The major limitation of this study was that only 50 % of the invitee
482, Page 2 of 6
for the study successfully completed the protocol. This may have introduced a self-selection bias favoring those with sleep disorder symptoms or hypertension, magnifying the association. However, statistical safeguards were taken to minimize the potential bias [11]. Another cross-sectional study reported on 2,677 adults aged 20–85 years seen at the sleep clinic of St. Michael’s Hospital in Canada who had undergone nocturnal polysomnography and blood pressure measurement by standard cuff pressure method. Hypertension was defined as either being on antihypertensive medications or having systolic BP greater than 140 mmHg or diastolic BP greater than 90 mmHg. One thousand four hundred twenty-six patients had obstructive sleep apnea as defined by AHI >10 events/h. One thousand two hundred forty-nine patients with AHI ≤10 served as controls. The prevalence of hypertension in the control group was 22.8 % and more than doubled to 53.6 % in those with AHI >50 events/h. Multiple logistic regression analysis including sex, age, BMI, and an interaction for BMI and AHI showed that an increase in AHI by one event/h which was associated with 1 % risk of having hypertension [12]. The 1 % estimate of risk for hypertension was lower than the 3.7 % previously reported by Young et al. [11]. This was attributed to the comparison group who were heavy snorers without OSA—snoring has been reported to be associated with increased levels of blood pressure. One of the largest cross-sectional studies ever reported was a component of the multicenter National Institutes of Healthfunded Sleep Heart Health Study that assessed the association between sleep-disordered breathing and hypertension in 6,132 community-dwelling adults aged ≥40 years. This study reported an odds ratio of 1.37 (95 % CI 1.03–1.83, P for trend= 0.005) using a multivariable analysis comparing the highest category of AHI ≥30/h with the lowest category (
PATHOGENESIS OF HYPERTENSION (W ELLIOTT, SECTION EDITOR)
Obstructive Sleep Apnea and Hypertension: a Critical Review Vahid Mohsenin
Published online: 20 August 2014 # Springer Science+Business Media New York 2014
Abstract Obstructive sleep apnea (OSA) is a prevalent sleep disorder which is characterized by recurrent upper closure with oxygen desaturation and sleep disruption. OSA increases the risk of vascular disorders in the form of stroke, myocardial infarction, congestive heart failure, and hypertension. The mechanisms underlying the vascular disorders are several and include intermittent hypoxia with release of cytokines, angiogenic inhibitors, free radicals, and adhesion molecules. During apneas, arterial blood pressure gradually rises and surges abruptly after the termination of apnea. Two thirds of patients with OSA will ultimately have diurnal hypertension. This review discusses the literature supporting the significant role of OSA in hypertension and the effect of OSA treatment on blood pressure. Keywords Obstructive sleep apnea . Hypertension . Endothelial dysfunction . Angiogenic inhibitors
Introduction Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder that affects 15–24 % of the adults and is associated with increased morbidity and mortality [1]. OSA is characterized by recurrent upper airway obstruction during sleep. These episodes are terminated by arousals and are commonly associated with hypoxemia. A growing body of evidence shows that OSA syndrome is independently associated with significant cardiovascular morbidity and mortality, including This article is part of the Topical Collection on Pathogenesis of Hypertension V. Mohsenin (*) Section of Pulmonary, Critical Care and Sleep Medicine, Yale University, P.O. Box 208057, LLCI 106, 15 York Street, New Haven, CT 06510, USA e-mail: [email protected]
coronary artery disease, heart failure, and stroke [2–4]. The acute hemodynamic and autonomic perturbations that accompany obstructive apneas during sleep, with associated arousals and intermittent hypoxemia, can lead to sustained diurnal hypertension in susceptible individuals, independent of other known risk factors for hypertension [5–8].
Prevalence of Hypertension in OSA Cross-sectional Studies OSA and hypertension are common, and many individuals have both conditions. The prevalence of hypertension in OSA ranges from 30 to 70 % [9]. An estimated 30 % of hypertensive patients also have OSA, often undiagnosed [9, 10]. Three large cross-sectional studies were reported between 1997 and 2000. The first report was a cross-sectional analysis of Wisconsin Sleep Cohort where 1,060 employed women (n=452) and men (n=617) aged 30 to 60 years who had an overnight polysomnography and blood pressure measurement were included. The multiple logistic regression analysis, with inclusion of apnea-hypopnea index (AHI), age, body mass index (BMI), and an interaction term for BMI and AHI, indicated that each additional apneas or hypopneas per hour of sleep increased the risk of having hypertension by 3.7 %. The odds ratios and 95 % confidence intervals (CIs) for hypertension associated with AHI levels of 5, 15, and 30 for BMI of 30 kg/m2 were 1.21 (95 % CI 1.09–1.34), 1.75 (95 % CI 1.28–2.40), and 3.07 (95 % CI 1.65–1.74), respectively. The odds ratios were attenuated with increasing BMI but remained statistically significant. This study showed that sleep-disordered breathing was associated with an increased prevalence of hypertension in employed middle-aged adults. It further demonstrated that the risk of hypertension was also present with a milder form of sleep-disordered breathing. The major limitation of this study was that only 50 % of the invitee
482, Page 2 of 6
for the study successfully completed the protocol. This may have introduced a self-selection bias favoring those with sleep disorder symptoms or hypertension, magnifying the association. However, statistical safeguards were taken to minimize the potential bias [11]. Another cross-sectional study reported on 2,677 adults aged 20–85 years seen at the sleep clinic of St. Michael’s Hospital in Canada who had undergone nocturnal polysomnography and blood pressure measurement by standard cuff pressure method. Hypertension was defined as either being on antihypertensive medications or having systolic BP greater than 140 mmHg or diastolic BP greater than 90 mmHg. One thousand four hundred twenty-six patients had obstructive sleep apnea as defined by AHI >10 events/h. One thousand two hundred forty-nine patients with AHI ≤10 served as controls. The prevalence of hypertension in the control group was 22.8 % and more than doubled to 53.6 % in those with AHI >50 events/h. Multiple logistic regression analysis including sex, age, BMI, and an interaction for BMI and AHI showed that an increase in AHI by one event/h which was associated with 1 % risk of having hypertension [12]. The 1 % estimate of risk for hypertension was lower than the 3.7 % previously reported by Young et al. [11]. This was attributed to the comparison group who were heavy snorers without OSA—snoring has been reported to be associated with increased levels of blood pressure. One of the largest cross-sectional studies ever reported was a component of the multicenter National Institutes of Healthfunded Sleep Heart Health Study that assessed the association between sleep-disordered breathing and hypertension in 6,132 community-dwelling adults aged ≥40 years. This study reported an odds ratio of 1.37 (95 % CI 1.03–1.83, P for trend= 0.005) using a multivariable analysis comparing the highest category of AHI ≥30/h with the lowest category (
