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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_4421_Библиотеки_им_академика_М_И_Перельмана.pdf
Health Consequences of Obstructive Sleep Apnea
Joseph Roland D. Espiritu
Contents
3.1 Cardiovascular Consequences – 25
3.1.1 Chronic Heart Failure – 25
3.1.2 Systemic Hypertension – 26
3.1.3 Coronary Heart Disease – 26
3.1.4 Arrhythmias – 28
3.1.5 Cerebrovascular Disease – 28
3.2 Respiratory Consequences – 29
3.2.1 Asthma – 29
3.2.2 Chronic Obstructive Pulmonary Disease – 29
3.2.3 Pulmonary Embolism – 29
3.2.4 Pulmonary Hypertension – 30
23
3
3.3 Endocrine andMetabolic Consequences – 30
3.3.1 Diabetes Mellitus – 30
3.3.2 Metabolic Syndrome – 30
3.3.3 Sexual Dysfunction – 31
3.4 Gastrointestinal Consequences – 31
3.4.1 Gastroesophageal Reux Disease – 31
3.4.2 Nonalcoholic Fatty Liver Disease – 31
3.5 Obstetric Outcomes – 32
3.5.1 Pregnancy-Related Hypertensive Disorders – 32
3.5.2 Gestational Diabetes – 32
3.5.3 Maternal Cardiovascular andPulmonary Complications – 32
3.5.4 Maternal Surgical Complications – 32
3.6 Perinatal Outcomes – 32
3.6.1 Impaired Fetal Growth – 32
3.6.2 Preterm Birth – 32
3.6.3 Small forGestational Age/Low Birthweight – 32
3.6.4 Stillbirth – 34
3.6.5 NICU Admission – 34
© Springer Nature Switzerland AG 2021
K. B. Kim et al. (eds.), Management of Obstructive Sleep Apnea, https://doi.org/10.1007/978-3-030-54146-0_3
3.7 Perioperative Outcomes – 34
3.8 Accident-Related Consequences – 35
3.9 Cancer-Related Outcomes – 35
3.10 Survival Outcomes – 36
3.10.1 Overall Mortality – 36
3.10.2 Cardiovascular Death – 36
3.10.3 Chronic Obstructive Pulmonary Disease Mortality – 36
3.10.4 Perioperative Mortality – 36
References – 39
Health Consequences ofObstructive Sleep Apnea
25
3
Core Message
5 Obstructive sleep apnea (OSA) adversely affects vir-
tually every organ system resulting in adverse health
outcomes:
– Neurocognitive consequences include impairments
in daytime alertness, attention/vigilance, delayed
long-term visual and verbal memory, visuospatial/
constructional abilities, and executive function
while neuropsychological ones include depression,
somatic syndromes, anxiety, and attention decit/
hyperactivity disorder.
– Cardiovascular consequences of OSA include CHF,
systemic hypertension, ischemic heart disease, atrial
brillation, ventricular arrhythmia, and stroke.
– Respiratory consequences include poor symptom
control in asthma, worse pulmonary function in
chronic obstructive pulmonary disease (COPD),
increased frequency of exacerbation in both asthma
and COPD, increased prevalence and recurrence of
pulmonary embolism, and a higher prevalence pulmonary hypertension.
– Endocrine consequences include diabetes mellitus,
metabolic syndrome, and sexual dysfunction in men
and women.
– Gastrointestinal consequences include gastroesopha-
geal reux disease and nonalcoholic fatty liver disease.
– Obstetric consequences include pregnancy-related
hypertensive disorders and gestational diabetes, as
well as maternal cardiovascular, pulmonary, and
surgical complications.
– Perinatal consequences include low birth weight,
preterm birth, NICU admission, and hyperbilirubinemia.
– Perioperative consequences include postoperative
ICU transfer, respiratory complications, cardiovascular events, and neurologic complications.
– Accident-related consequences include motor vehi-
cle crashes and work-related injuries.
– Oncologic consequences include increased cancer
incidence including breast and colorectal cancer.
– Mortality-related consequences include higher
death rates overall and from cardiovascular, noncardiovascular, and COPD-related causes.
5 Nocturnal respiratory dysfunction (i.e., hypoxemia-
reoxygenation and hypercapnia), poor sleep quality (i.e., increased arousals, poor sleep efciency, and
altered sleep architecture), and intrathoracic pressure
variations, in addition to shared comorbid risk factors,
result in oxidative stress, inammation, sympathetic
activation, endothelial dysfunction, neurohormonal
changes, thrombophilia, and hemodynamic changes,
which are the pathophysiologic mechanisms for these
adverse clinical outcomes.
Obstructive sleep apnea (OSA) is associated with a growing number of adverse health outcomes (. Fig. 3.1).
This chapter will quantify the risks and describe the
mechanisms behind the association between OSA
and various adverse cardiovascular, cerebrovascular,
respiratory, endocrine and metabolic, gastrointestinal,
obstetric, perinatal, perioperative, accident-related,
oncologic, and survival outcomes. This literature review
is limited to OSA and includes neither the health consequences of other types of sleep-related breathing disorders (SRBD) such as snoring, central sleep apnea, or
sleep-related hypoventilation or hypoxemia disorders
nor the efcacy of various OSA therapies (e.g., CPAP)
on these consequences. Neurocognitive (i.e., hypersomnolence, fatigue, impairments in attention/vigilance,
delayed long-term visual and verbal memory, visuospatial/constructional abilities, and executive function)
[13] and neuropsychological (e.g., depression, somatic
syndromes, anxiety, and attention decit/hyperactivity
disorder) dysfunction due to OSA is discussed in detail
in 7
Chap. 7.
3.1 Cardiovascular Consequences
The Sleep Heart Health Study (SHHS), a crosssectional, population-based epidemiologic study utilizing domiciliary polysomnography (PSG), described the
association between OSA and cardiovascular disease
in community-dwelling, middle-aged adults in the
United States [92]. The SHHS revealed an apparent
dose–response relationship between the severity of
OSA based on the apnea–hypopnea index (AHI) or
duration of nocturnal hypoxemia (SpO2<90%) and the
prevalence of cardiovascular diseases, even after
adjusting for known risk factors such as age, sex, body
mass index (BMI), systemic hypertension, and highdensity lipoprotein [100]. Since the publication of the
SHHS study, several meta-analyses had corroborated
the association between OSA and cardiovascular disease (. Table3.1).
3.1.1 Chronic Heart Failure
Of all the cardiovascular comorbidities, the SHHS
reported chronic heart failure (CHF) had the strongest
association with OSA [100]. The highest quartile of
AHI severity (>11/hr) had the strongest relationship
with heart failure. To date, there are no prospective
cohort studies comparing the incidence of CHF in OSA
patients with controls.
26
J. R. D. Espiritu
Neurocognitive and Neuroaffective
• Sleepiness
• Fatigue
• Neurocognitive dysfunction
• Depression
• Attention-deficit/hyperactivity
3
disorder
• Motor vehicle crashes
• Occupational accidents
Mortality
• Overall
• Cardiovascular-related
• Noncardiovascular
• COPD (Overlap syndrome)-related
Cardiovascular
• CHF
• Systemic hypertension
• Coronary heart disease
• Atrial fibrillation
• Ventricular arrhythmias
• Sudden unexpected
nocturnal death
• Stroke
Metabolic and Endocrine
• Diabetes mellitus
• Metabolic syndrome
• Sexual dysfunction
Obstetric and Perinata
• Preeclamspsia
• Gestational
hypertension
• Gestational diabetes
• Surgical complications
• Low birth weight
• NICU admission
• Hyperbilirubinemial
. Fig. 3.1 Organ-based adverse health consequences of obstructive sleep apnea
Pulmonary
• Asthma exacerbation
• COPD respiratory
dysfunction
• Pulmonary embolism
• Pulmonary hypertension
GI Complications
• GERD
• Nonalcoholic fatty liver
disease
Surgical Complications
• ICU transfer
• Respiratory
complications
• Cardiovascular events
• Neurologic
complications
3.1.2 Systemic Hypertension
The SHHS reported a higher prevalence of systemic
hypertension in participants with OSA (AHI≥5/hr) or
nocturnal hypoxemia (SpO2<90% for ≥12% of the total
sleep time) compared to controls [82]. In contrast, a prospective cohort analysis of SHHS data did not nd an
increased incidence of hypertension after controlling for
BMI [83]. Nevertheless, a meta-analysis of six studies
with 20,637 participants conrmed a statistically signicantly increased incidence of systemic hypertension in
OSA, regardless of severity [71]. A more recent metaanalysis reported increasing odds ratio of systemic
hypertension with worsening severity of OSA [36].
OSA also has a strong association with treatmentrefractory hypertension in patients with chronic kidney
disease. The Sleep-SCORE study conducted unattended
home PSG and monitored automated blood pressure
(BP) in 88 end-stage renal disease (ESRD) patients not
receiving dialysis, and demonstrated a signicant association between the severity of sleep apnea and resistant
hypertension (BP ≥140/90 mmHg on ≥3 BP medications) in those with ESRD on dialysis (but not in those
without CKD or in those with CKD not on dialysis) [1].
A more recent meta-analysis by Hou etal. demonstrated
a statistically signicant association between OSA and
resistant-hypertension [36].
3.1.3 Coronary Heart Disease
Based on the cross-sectional analysis of the SHHS, there
appeared to be no increase in the prevalence of selfreported coronary heart disease (CHD) in OSA [100].
Subsequent meta-analyses reported conicting results
on the association between OSA and CHD.The rst 2
meta-analyses of prospective studies by Loke and Dong,
respectively, did not nd an association between OSA
and new-onset CHD [20, 64]. In contrast, one metaanalysis reported a doubling of the risk of a recurrent
ischemic event [121] and nonfatal cardiovascular events
in patients with OSA [23]. There was also an increased
Health Consequences ofObstructive Sleep Apnea
. Table 3.1 Strength of association between obstructive sleep apnea and cardiovascular outcomes
27
3
Cardiovascular outcomes Strength of association, point estimate (95% condence
interval)
Congestive heart failure aOR=2.38 (1.22, 4.62) overall
aOR=1.19 (0.56, 2.53) for AHI=1.3–4.3/hr
aOR=1.96 (0.99, 3.90) for AHI=4.4 to <10.9/hr
aOR=2.20 (1.11, 4.37) for AHI≥11/hr.
Systemic hypertension OR=1.37 (1.03, 1.83) comparing highest (AHI≥30/hr) vs.
lowest (AHI <1.5/hr) categories
OR=1.41 (1.29, 1.89) comparing highest (≥12%) vs.
lowest (0.05%) categories of percentage of sleep time below
90% oxygen saturation
aOR=1.51 (0.93–2.47) for AHI>30/hr
OR=1.26 (1.17, 1.35) for mild OSA
OR=1.50 (1.27, 1.76) for moderate OSA
OR=1.47 (1.33, 1.64) for severe OSA
OR=1.18 (1.09, 1.27) mild OSA
OR=1.32 (0.86, 1.20) moderate OSA
OR=1.56 (1.29, 1.83) severe OSA
Resistant hypertension aOR 3.5 (0.8, 15.4) in non-CKD
aOR=1.2, (0.4, 3.7) in nondialysis CKD
aOR=7.1, (2.2, 23.2) in ESRD on dialysis
OR=2.84 (1.7, 3.98) in all OSA patients
Coronary heart disease aOR=1.27 (0.99, 1.62)
OR=1.56 (0.83, 2.91)
OR=1.92 (1.06, 3.4) in 5 male- predominant studies
RR=1.37 (0.95–1.98)
RR=2.06 (1.13, 3.77) for recurrent ischemic heart disease
Cardiovascular disease RR=2.48 (1.98, 3.10)
RR=1.79 (1.47, 2.18) for severe OSA
Nonfatal cardiovascular
events
Cardiovascular events
after percutaneous
coronary intervention
Subclinical cardiovascular
disease
Nocturnal atrial and
ventricular arrhythmias
Prevalent atrial brillation aOR=4.02 (1.03, 15.74)
Incident atrial brillation HR=2.18 (1.34, 3.54) [27] Retrospective cohort
Atrial brillation
recurrence after catheter
ablation
Atrial brillation
post- coronary artery
bypass grafting
Nonsustained ventricular
tachycardia
OR=2.46 (1.80, 3.36) [23] Meta- analysis
RR=1.59 (1.22, 2.06) [128] Meta- analysis
aOR range=1.036–2.21 for coronary artery calcium [2] Systematic review
Prevalence ratio=1.04 (1.01, 1.07) [17] Prospective cohort
OR=2.15 (1.19, 3.89) in older men in the highest RDI
quartile
RR=1.25 (1.08, 1.45)
OR=1.70 (1.40, 2.06)
OR=2.38 (1.57, 3.62) [90] Systematic review and
OR=3.40 (1.03, 11.20)
aOR=1.07 (1.02, 1.12) in hypertrophic obstructive
cardiomyopathy patients
References Study design
[100] Cross- sectional
[36, 71, 82,
83]
[1, 36] Prospective cohort
[20, 64, 100,
121]
[20, 115] Meta- analysis
[69, 70] Cross- sectional
[18, 79] Meta- analysis
[69, 113] Cross- sectional
Cross- sectional
Prospective cohort
Meta- analysis
Systematic review and
meta- analysis
Systematic review and
meta- analysis
Cross- sectional
Meta- analysis
Meta- analysis
Meta- analysis
Meta- analysis
study
Cross- sectional
Meta- analysis
meta- analysis
Cohort study
(continued)
28
J. R. D. Espiritu
. Table 3.1 (continued)
Cardiovascular outcomes Strength of association, point estimate (95% condence
interval)
Complex ventricular
3
ectopy
Ventricular arrhythmias OR=5.6 (2.0, 15.6) in patients with
Stroke aOR=1.42 (1.13, 1.78)
Abbreviations: aOR adjusted odds ratio, OR odds ratio, AHI apnea–hypopnea index, CKD chronic kidney disease, ESRD end-stage
renal disease, RR relative risk or risk ratio, HR hazard ratio, aHR adjusted hazard ratio
incidence of acute coronary events after percutaneous
coronary intervention in OSA patients [128]. Noninvasive
studies investigating subclinical cardiovascular disease
described an increased occurrence of atherosclerosis
(i.e., coronary artery calcication, carotid intima thick-
OR=1.74 (1.11, 2.74) [69] Cross- sectional
cardioverter- debrillator
aOR=1.02 (0.98, 1.07) in a national inpatient sample
OR=2.24, (1.57, 3.19)
RR=2.02 (1.40, 2.90)
RR=2.15 (1.42, 3.24) for severe OSA
OR=1.94, (1.29, 2.92)
RR=2.15 (1.42, 3.24) in severe OSA
aHR=1.94 (1.31, 2.89)
although a cross- sectional analysis of a national inpatient sample showed a higher prevalence of ventricular
arrhythmias in hospitalized OSA patients, no signicant
association was determined after adjusting for cardiovascular risk factors [96].
References Study design
[96, 126] Prospective cohort
Cross- sectional study
[20, 58, 64,
100, 115,
118, 121]
Cross- sectional
Meta- analysis
Meta- analysis
Meta- analysis
Meta- analysis
Meta- analysis
Meta- analysis
ness, brachial artery ow-mediated dilatation, and pulse
wave velocity) in OSA subjects [2].
3.1.5 Cerebrovascular Disease
3.1.4 Arrhythmias
Arrhythmias are perceived to occur more commonly in
patients with OSA. A population study in Brazil
reported an increased occurrence of nocturnal atrial
and ventricular arrhythmias on polysomnography [17].
According to a 5-year retrospective cohort study, the
risk of incident atrial brillation (AF) was doubled in
OSA subjects, particularly those younger than 65years,
even after controlling for cardiovascular risk factors
[27]. Nocturnal hypoxemia was found to be a signicant
predictor of new-onset AF. The risk of AF after coronary artery bypass grafting was also signicantly
increased in OSA [90]. In addition, recurrence of AF
after catheter ablation therapy appeared to also be
higher with OSA [18, 79].
A systematic review of 22 studies by Raghuram
et al. reported an elevated risk of ventricular ectopy
and arrhythmias [93]. OSA was associated with a
higher prevalence of nonsustained ventricular tachycardia (NSVT) [69]. The severity of AHI correlated with
the prevalence of NSVT in patients with hypertrophic
obstructive cardiomyopathy [113]. On the other hand,
There is an increased prevalence of SRBD in patients
diagnosed with cerebrovascular disease (CVD), with
estimates ranging from 71 to 72% for an AHI>5/hr.
and 20–30% [98] for AHI>20/hr. [42, 98]. The predom-
inant type of SRBD was OSA, with only 7% having
primarily central apnea [42]. Factors associated with
SRBD in stroke were male gender, recurrent strokes,
and an idiopathic etiology, but not event type (ischemic
vs. hemorrhage), timing after stroke, or type of monitoring [42]. The cross-sectional analysis of the SHHS
data also reported a strong association between stroke
and OSA [100]. Conversely, four subsequent metaanalyses had conrmed the higher incidence of stroke
in OSA patients. Li and colleagues reported a doubling
of the risk of incident fatal and nonfatal strokes in
patients with OSA [58]. Loke etal. corroborated this
association but reported that most studies primarily
enrolled men [64]. Xie and colleagues conrmed that
OSA patients with a history of CVD or CHD had a
signicantly higher risk of stroke [121]. A meta-analysis of prospective cohort studies involving three million participants corroborated the increased incidence
of cerebrovascular disease, even after controlling for
Health Consequences ofObstructive Sleep Apnea
29
3
known risk factors [118]. The risk of stroke appeared
to be related to the severity of OSA, that is, a higher
stroke risk in moderate- to- severe OSA but not in mild
OSA [115].
3.2 Respiratory Consequences
3.2.1 Asthma
Asthmatic patients are more than twice as likely to have
OSA, especially with higher BMI [51, 59] (. Table3.2).
OSA may aggravate asthma control and increase asthma
exacerbation frequency [110, 116].
3.2.2 Chronic Obstructive Pulmonary
Disease
The prevalence of OSA in patients with chronic obstructive pulmonary disease (COPD) ranges anywhere from
10 to 66% depending on the population sample [22]. A
prospective cohort study demonstrated that comorbid
OSA in COPD patients was associated with a signicantly higher frequency of hospitalization due to severe
exacerbation [67]. The overlap of OSA and COPD is
associated with worse diurnal and nocturnal lung function (i.e., hypoxemia, hypercapnia, and 6-minute walk
distance) and polysomnographic ndings [i.e., worse
AHI and oxygen desaturation index (ODI), nocturnal
hypoxemia, sleep efciency, arousal index, and sleep
architecture].
3.2.3 Pulmonary Embolism
Patients diagnosed with venous thromboembolism
(VTE) have a signicantly higher prevalence of OSA.A
nested case–control study found patients, especially
women, with VTE had more than double the odds of
having OSA even after adjusting for thrombophilic risk
factors [5]. More than half of acute pulmonary embolism (PE) survivors had OSA [8, 52]. OSA may well be
considered a thrombophilic condition. A case–control
study of 209 patients found a higher prevalence of PE in
patients with OSA [3]. The same investigators followed
120 PE patients who had stopped their anticoagulation
for 5 to 8years and demonstrated a 20-fold higher incidence of recurrent PE [4]. A population-based, retrospective cohort study reported that OSA patients were
more likely to suffer from VTE (deep venous thrombosis
and PE) [88]. A retrospective cohort study at the Mayo
Clinic revealed heightened risks of occurrence, as well as
recurrence of PE in OSA patients [97]. Moreover, highrisk PE is more likely to occur in those with moderateto- severe OSA [8, 52]. A diagnosis of OSA may worsen
pulmonary artery thrombus load and disease severity in
. Table 3.2 Strength of association between obstructive sleep apnea and pulmonary outcomes
Pulmonary outcomes Strength of association, point estimate
(95% condence interval)
Asthma OR=1.92 (1.34, 2.76)
OR=3.73 (2.90, 4.57)
Asthma exacerbation aOR=1.322 (1.148, 1.523) with AHI
aOR=3.4 (1.2, 10.4)
COPD exacerbation
requiring hospitalization
Deep venous thrombosis HR=3.50 (1.83, 6.69) [88] Longitudinal, nationwide,
Pulmonary embolism aOR=3.7 (1.3, 10.5)
Recurrent pulmonary
embolism
Abbreviations: aOR adjusted odds ratio, AHI apnea–hypopnea index, COPD chronic obstructive pulmonary disease, RR relative risk
or risk ratio, HR hazard ratio, aHR adjusted hazard ratio
RR=1.70 (1.21, 2.38) [67] Prospective cohort
HR=3.97 (1.85, 8.51)
aOR=1.44 (1.07, 1.90)
aHR=20.73 (1.71, 251.28)
aOR=2.21 (1.05, 4.68)
References Study design
[51, 59] Meta- analysis
Meta- analysis
[110, 116] Case–control
Retrospective cohort
population-based cohort
[3, 88, 97] Prospective cohort
Longitudinal, population-based
cohort
Retrospective cohort
[4, 97] Prospective cohort
Retrospective cohort
30
J. R. D. Espiritu
acute PE [31]. However, the transient increase in central
venous pressure after an acute PE does not seem to
3.3 Endocrine andMetabolic
Consequences
affect OSA severity once patients are clinically stable to
undergo PSG [7]. The severity of OSA based on the
AHI and time spent with SpO2<90% were independent
predictors of recurrent PE risk. The proposed mecha-
3
nisms for this increased VTE risk include the heightened
blood viscosity, clotting factors, tissue factor, platelet
activity, and whole blood coagulability, as well as the
attenuated brinolysis in OSA [60].
3.3.1 Diabetes Mellitus
The SHHS and the Atherosclerosis Risk in Communities
Study corroborated a signicantly increased 13-year incidence of DM in patients with severe OSA patients [77]
(. Table3.3). A meta-analysis of six prospective cohort
studies conrmed this link between DM in severe OSA
[114]. Diabetic microvasculopathy appeared to be aggra-
3.2.4 Pulmonary Hypertension
The prevalence of SRBD tends to be much higher in
patients with pulmonary hypertension (PH). One study
found a 71% SRBD prevalence in patients with pulmonary arterial hypertension, with 56% having OSA [72].
vated by OSA.A meta-analysis of longitudinal and crosssectional studies determined a 73% greater risk of diabetic
nephropathy with OSA [57]. A subsequent meta-analysis
by the same investigators also found a higher occurrence
of diabetic retinopathy and maculopathy, which correlated with the duration of nocturnal hypoxemia [56].
Conversely, there is a disproportionately higher prevalence of PH in OSA patients, with estimates ranging
from 17 to 67% [47, 95]. A study employing right heart
3.3.2 Metabolic Syndrome
catheterization (RHC) in 220 consecutive OSA calculated a PH prevalence of 17% [15]. PH occurrence in
this RHC study was attributed to the comorbid
obstructive ventilatory abnormality with associated
hypoxemia and hypercapnia rather than the severity of
OSA. In contrast, an echocardiographic study determined that a nadir SpO
<70% rather than the AHI
2
was a good predictor of PH [117]. A meta-analysis of
studies employing echocardiography demonstrated a
higher prevalence of RV dilatation, hypertrophy, and
dysfunction in OSA [68].
The metabolic syndrome is dened by the cluster of high
blood pressure, diabetes, hypercholesterolemia, and
abdominal obesity. Two meta-analyses estimated a twoto-threefold increased risk of metabolic syndrome in
OSA [91, 122]. Nadeem etal. singled out the AHI as a
signicant independent predictor of hypercholesterolemia and hypertriglyceridemia [75]. OSA is also associated with elevated leptin levels, nocturnal hypoxemia,
impaired glucose tolerance, and increased C-reactive
protein level independent of BMI [6, 43].
. Table 3.3 Strength of association between obstructive sleep apnea and endocrine and metabolic outcomes
Metabolic disease outcomes Strength of association, point estimate
(95% condence interval)
Diabetes mellitus type 2 RR=1.22 (0.91, 1.63) for mild OSA
RR=1.63 (1.09, 2.45) for
moderate-to- severe OSA
HR=1.71 (1.08, 2.71)
Diabetic kidney disease OR=1.73 (1.13, 2.64) [57] Meta- analysis
Diabetic retinopathy OR=0.91(0.87–0.95) with minimum
oxygen saturation
Metabolic syndrome OR=2.87 (2.41, 3.42)
OR=2.56 (1.98, 3.31)
aOR=1.97 (1.34, 2.88)
Erectile dysfunction RR=1.82 (1.12, 2.97)
OR=2.22 (1.41, 5.55)
Female sexual dysfunction RR=2.00 (1.29, 3.08) [62] Meta- analysis
Abbreviations: RR relative risk or risk ratio, HR hazard ratio, OR odds ratio, aOR adjusted odds ratio
References Study design
[77, 114] Meta- analysis
Prospective cohort
[56] Meta- analysis
[91, 122] Meta- analysis of cross- sectional studies
Meta- analysis of case- control studies
Meta- analysis
[45, 62] Meta- analysis
Systematic review and meta- analysis
Health Consequences ofObstructive Sleep Apnea
31
3
3.3.3 Sexual Dysfunction
Meta-analyses on the association of OSA and sexual
function calculated a doubling of the risk of erectile
dysfunction in men and sexual dysfunction in women,
respectively [45, 62]. A systematic review by Steinke and
colleagues determined that in addition to altered hormone levels, the duration of nocturnal hypoxemia signicantly predicted sexual dysfunction in women while
BMI and inammatory markers were signicant predictors in men [109].
3.4 Gastrointestinal Consequences
3.4.1 Gastroesophageal Reux Disease
OSA patents are at a 1.75- to twofold higher risk of gastroesophageal reux disease (GERD) [32, 119] and a
threefold higher risk of nocturnal GERD [125]
(. Table 3.4). Nocturnal GERD correlated with the
severity of OSA [106]. You et al.’s endoscopic-based
investigation observed a higher occurrence of nonero-
sive, but not in erosive, esophagitis in OSA [125]. OSA
also appeared to be associated with Barrett’s esophagitis, with the risk related to the AHI severity [33, 55].
Conversely, GERD symptoms can aggravate sleepdisordered breathing, resulting in higher AHI, longer
maximum apnea duration, lower minimum oxygen saturation, higher ODI, and poorer sleep efciency [48].
Gastroesophageal reux events usually occur after
spontaneous awakenings and arousals rather than after
disordered-breathing events [39, 124]. Utilizing highresolution esophageal manometry and 24-hr. esophageal pH-impedance monitoring, Shepherd et al.
identied obesity to be the mediator of reux events in
OSA [105].
3.4.2 Nonalcoholic Fatty Liver Disease
The presence of OSA approximately doubled the likelihood of a histological, chemical, or radiographic diagnosis of nonalcoholic steatohepatosis, steatohepatitis,
and hepatic brosis [74, 107]. Elevations in ALT, but not
AST, levels signicantly correlated with the AHI [41].
. Table 3.4 Strength of association between obstructive sleep apnea and gastrointestinal outcomes
Gastrointestinal disease outcome Strength of association, point estimate (95%
condence interval)
GERD aOR=2.13 (1.17, 3.88)
OR=1.75 (1.18, 2.59)
Non- erosive gastroesophageal
reux
Erosive gastroesophageal reux
Nocturnal GERD aOR=2.97 (1.19, 7.84)
Barrett’s esophagitis aOR=1.2 (1.0, 1.3) per 10-unit increase in AHI
Nonalcoholic fatty liver disease:
Fatty liver
Inammation
Fibrosis
Nonalcoholic fatty liver disease:
Histology
Radiology
Elevated AST or ALT
NASH, any stage
Fibrosis
Advanced brosis
aOR=1.82 (1.15, 2.90)
aOR=0.93 (0.56, 1.55)
aOR=1.84(1.28, 2.63) for moderate OSA
aOR=2.39 (1.71, 3.33) for severe OSA
OR=3.26 (1.72, 6.85) per 10-unit increase in AHI
OR=2.556 (1.184, 5.515
OR=1.800 (0.905, 3.579)
OR=2.586 (1.289, 5.189)
OR=2.01 (1.36, 2.97)
OR=2.34 (1.71, 3.18)
OR=2.53 (1.93, 3.31)
OR=2.37(1.59, 3.51)
OR=2.16 (1.45, 3.20)
OR=2.30 (1.21, 4.38).
References Study design
[32, 119] Cross- sectional
[125] Cross- sectional
[106, 125] Cross- sectional
[33, 55] Cross- sectional
[107] Meta- analysis
[74] Meta- analysis
population- level analysis
Meta- analysis
Cross- sectional
Retrospective cohort
Abbreviations: GERD gastroesophageal reux disease, aOR adjusted odds ratio, OR odds ratio, AST aspartate aminotransferase, ALT
alanine aminotransferase, NASH nonalcoholic steatohepatosis
32
J. R. D. Espiritu
The predisposition for nonalcoholic fatty liver disease in
OSA patients is expected given the shared risk factors
(e.g., obesity) and comorbid conditions (e.g., DM and
metabolic syndrome).
3
3.5 Obstetric Outcomes
3.5.1 Pregnancy-Related Hypertensive
Disorders
Pregnancy-related hypertensive disorders (i.e., preeclampsia, gestational hypertension, and eclampsia)
occurred more frequently in pregnant women with
OSA [63]. Several studies had corroborated a 2- to
threefold increased risk of preeclampsia in gravid
women with OSA [10, 19, 38, 63, 123] (. Table3.5).
Virtually all of the studies found a significant association between OSA and gestational hypertension.
A national cohort study observed a threefold
increased incidence of eclampsia in pregnant women
with OSA [10].
3.5.2 Gestational Diabetes
The odds of developing gestational diabetes were 1.5–
4.7 times greater in pregnant women with OSA [10, 19,
37]. Reutrakul etal. identied arousal index and ODI as
signicant independent predictors of impaired glucose
tolerance in pregnancy with OSA [94]. Pathophysiologic
mechanisms behind gestational diabetes in OSA patients
include maternal sleep disruption, intermittent hypoxemia, oxidative stress, inammation, catecholaminergic
activation, peripheral vasoconstriction, and endothelial
dysfunction.
3.5.3 Maternal Cardiovascular
andPulmonary Complications
A nationwide cohort study of 1,577,632 gravidas in the
United States recorded a signicantly higher occurrence
of adverse cardiovascular events such as pulmonary
edema, CHF, and cardiomyopathy in pregnant women
with OSA [10]. Although there was a vefold increase in
the odds of PE or pulmonary infarction in pregnant
women with OSA, the difference was not statistically
signicant [10]. The incidence of peripartal stroke was
also not increased [10].
3.5.4 Maternal Surgical Complications
Although a small prospective cohort study found no difference in the need for caesarean delivery when using the
Berlin Questionnaire to screen for OSA [50], subsequent
prospective studies [65, 108] and a meta-analyses of
cohort studies [123] observed signicantly higher rates
of both elective and emergent caesarean delivery in
pregnant women with OSA.
Two studies on wound complications after delivery
showed conicting results, with a prospective cohort
study [65] showing no increase while a large retrospective national cohort study reporting a signicant increase
[10]. The same national cohort study reported higher
rates of maternal hysterectomy and ICU admission and
a longer length of stay but no difference in blood transfusion requirement [10].
3.6 Perinatal Outcomes
3.6.1 Impaired Fetal Growth
Studies on the effect of OSA on fetal growth have conicting results. A prospective cohort study of 26 high- and 15
low-OSA risk pregnant women did not nd a signicant
association between OSA and fetal growth after adjusting
for BMI [25] (. Table 3.6). In contrast, a case–control
study and a meta-analysis of 24 studies found a signicant association between maternal OSA and impaired
fetal growth [19, 49]. However, a national cohort study of
more than 1.5 million gravidas did not corroborate the
association between maternal OSA and fetal growth [10].
3.6.2 Preterm Birth
An earlier prospective cohort study of 175 obese pregnant women found no association between OSA and
preterm birth in neonates of women with OSA [65]. In
contrast, three subsequent meta-analyses reported a signicant doubling of the risk of preterm birth in neonates
of pregnant women with OSA [12, 19, 123].
3.6.3 Small forGestational Age/Low
Birthweight
Although a prospective cohort study of Korean pregnant women reported no association between suspected maternal OSA (based on the Berlin