Module 5 - Consequences of Sleep Disordered Breathing

Question 1

What are the primary effects of OSA on cerebral function in children and adolescents?

Answer 1

OSA impacts cerebral function primarily in children and adolescents due to their developing brains. Sleep loss contributes more to neurocognitive deficits than hypoxemia.

Question 2

Why is it unclear whether OSA has functional or anatomical consequences?

Answer 2

The effects of decreased alertness on higher cognitive functioning mimic cerebral damage from hypoxia. Daytime sleepiness measures are also not associated with objective measures of apnea burden, like AHI, hypoxemia, or sleep parameters.

Question 3

What cerebrovascular diseases can a high apnea burden cause?

Answer 3

High apnea burden can cause cerebrovascular diseases such as stroke.

Question 4

What are the effects of CPAP therapy on cerebral function?

Answer 4

CPAP reduces both objective and subjective daytime sleepiness and improves executive functioning. However, it does not alleviate depression symptoms, which occur in 40% of OSA patients. In younger patients with good compliance, CPAP can normalize all aspects of brain function.

Question 5

What cardiovascular diseases are associated with OSA?

Answer 5

OSA is associated with coronary artery disease (CAD), heart failure (HF), and cerebrovascular diseases such as stroke, with an incidence rate between 30-50% in patients with these conditions.

Question 6

How do OSA and cardiovascular diseases interact pathophysiologically?

Answer 6

The interaction is complex, but oxidative stress and endothelial dysfunction are key mechanisms leading to cardiovascular diseases in OSA. OSA also increases sympathetic activity.

Question 7

What is the relationship between OSA and arterial hypertension?

Answer 7

OSA is an independent risk factor for arterial hypertension, which in turn is a risk factor for CAD, HF, and stroke. This makes it challenging to prove a causal relationship between OSA and CVD independent of hypertension.

Question 8

How does CPAP therapy affect cardiovascular function in OSA patients?

Answer 8

CPAP reduces nocturnal sympathetic activation, oxidative stress, endothelial dysfunction, leptin levels, interleukins, CRP, platelet aggregability, and fibrinogen levels. It also lowers nocturnal and diurnal blood pressure in OSA.

Question 9

What is the relationship between metabolic syndrome and obesity?

Answer 9

Metabolic syndrome, defined by a large waist, high BP, high fasting BG, and reduced HDL cholesterol, is strongly associated with obesity and its sequelae, contributing to cardiovascular risk.

Question 10

How does white adipose tissue affect cardiovascular health?

Answer 10

White adipose tissue releases leptins and acids that contribute to inflammation and negative cardiovascular effects. In obesity, adipose tissue secretion is increased and altered due to relative hypoxia of adipocytes, particularly in intra-abdominal or visceral adipose tissue.

Question 11

How does sleep affect metabolic syndrome?

Answer 11

Sleep restriction in healthy individuals causes insulin resistance, reduced leptin, increased ghrelin concentrations, and increased appetite. Chronic stress also alters energy uptake, leading to obesity.

Question 12

How does OSA impact metabolic syndrome?

Answer 12

OSA is associated with a fivefold increase in metabolic syndrome. Leptin levels correlate with OSA severity, but causality is unclear due to the confounding effects of obesity.

Question 13

How does CPAP therapy affect metabolic status?

Answer 13

CPAP improves glucose control and insulin sensitivity in non-diabetic patients. In overweight and Type 2 diabetes patients, CPAP has no significant effect on metabolic status.

Question 14

How can weight loss improve OSA and metabolic outcomes?

Answer 14

A clinically meaningful reduction in body weight by about 20kg, coupled with counseling and a low-energy diet, improves OSA by over 60% and subsequently enhances metabolic outcomes.

Question 15

What are the known consequences of CSA in heart failure patients?

Answer 15

Unlike OSA, the consequences of CSA in HF patients are unclear. Patients with HF have less daytime sleepiness than controls despite reduced total sleep time, and no correlation between ESS and AHI in HF, though there is a correlation between ESS and severity of HF.

Question 16

What changes occur in sleep stages with CSA treatment?

Answer 16

Treatment leads to less Stage N1 sleep and more Stage N2 sleep, with no significant effect on SWS, REM, or arousals. It’s uncertain whether CSA profoundly disturbs sleep or only affects conventional sleep scoring.

Question 17

Why is it difficult to study the neurobehavioral impacts of CSA in heart failure patients?

Answer 17

HF patients tend to be elderly, which disturbs sleep, and both HF and age affect general health and sleep quality. The relationship is partly due to oxidative stress and sympathetic activation.

Question 18

How do the cardiovascular effects of CSA differ from those of OSA?

Answer 18

CSA is primarily associated with severe HF, and the oscillation of ventilation, HR, and SaO2 in CSA is distinct from OSA’s negative pressure swings and consecutive hypoxia. A failing heart is more vulnerable to stressors like increased BP and sympathetic activation, making OSA particularly detrimental in patients with established HF.

Question 19

Are the cardiovascular consequences of CSA in HF patients clear?

Answer 19

The cardiovascular consequences of CSA are unclear, and it’s uncertain if CSA contributes to morbidity and mortality in CHF patients or is merely a phenomenon.

Question 20

What effect does CPAP have on CSA?

Answer 20

CPAP reduces CSA by around 50%.

Question 21

What is the relationship between CSA and neurobiological sequelae and CV sequelae?

Answer 21

There is no clear relationship between CSA and neurobiological sequelae, and the CV sequelae of CSA are not well established compared to OSA.

Question 22

How does OSA impact the normal physiological changes during NREM sleep?

Answer 22

OSA disrupts the normal decrease in metabolic rate, sympathetic nerve activity, blood pressure, and heart rate, along with the increase in vagal tone. Cycles of hypoxia and CO2 retention alter sympathetic and parasympathetic activity, increasing ventilatory drive and creating negative intrathoracic pressure.

Question 23

What are the cardiac effects of negative intrathoracic pressure during OSA?

Answer 23

Negative intrathoracic pressure increases right ventricular (RV) preload and pulmonary vasoconstriction, which can cause the right ventricle to dilate and bulge into the left ventricle (LV), impairing LV filling and reducing stroke volume. It also increases the transmural pressure across the LV walls, increasing effective afterload

Question 24

How does OSA impact sympathetic and parasympathetic tone?

Answer 24

OSA increases sympathetic tone, raising systemic vascular resistance. Apnea termination arousals are associated with increased sympathetic tone and decreased vagal tone, leading to higher blood pressure and heart rate. High sympathetic tone persists during wakefulness and impairs vagally mediated heart rate variability.

Question 25

How does intermittent hypoxia contribute to cardiovascular risks in OSA?

Answer 25

Intermittent hypoxia triggers oxygen free radical production and activates inflammatory pathways, predisposing patients to atherosclerosis and thrombosis.

Question 26

How do coexisting conditions affect the mortality data for OSA?

Answer 26

Conditions like hypertension and obesity complicate the analysis of OSA's impact on survival. Most mortality data come from retrospective or observational studies, which may have referral bias or lack sufficient data on severe OSA.

Question 27

What did an early retrospective study by He reveal about survival and OSA in regard to treatment?

Answer 27

The study showed decreased survival in untreated patients with an AHI > 20/hr and unchanged survival when treated.

Question 28

How do cardiovascular diseases impact OSA patients' mortality?

Answer 28

An OSA study from 1976 to 1988 found that 53% of deaths were due to respiratory or cardiovascular causes. Additionally, the risk of mortality is higher for patients with moderate or severe OSA compared to the general population, with the presence of comorbidities further increasing this risk.

Question 29

How does the severity of OSA affect mortality in patients of different ages?

Answer 29

In patients younger than 62 years, increased mortality is associated with heart failure or diabetes mellitus. In those older than 62 years, predictors include COPD, congestive heart failure, and diabetes mellitus. However, older patients with mild to moderate OSA seem resistant to the adverse effects of OSA on mortality.

Question 30

What relationship exists between OSA and all-cause mortality?

Answer 30

Multiple studies indicate an increase in all-cause mortality associated with moderate to severe OSA, with an increased risk of cardiovascular events and mortality for severe OSA compared to those with normal sleep, snorers, or mild OSA.

Question 31

What is the gender difference in mortality risk for OSA patients?

Answer 31

Studies show strong evidence of increased mortality in untreated middle-aged male patients with severe OSA. Women with severe OSA may also face increased mortality, though the evidence is not as strong.

Question 32

How do sleepiness symptoms correlate with OSA's adverse outcomes?

Answer 32

Studies indicate that adverse outcomes correlate more with measures of oxygenation than sleepiness, suggesting that intermittent hypoxemia, rather than sleep fragmentation, is associated with increased mortality. The Wisconsin-based cohort found increased cardiovascular mortality with severe OSA, regardless of sleepiness symptoms.

Question 33

How does the timing of death differ for OSA patients?

Answer 33

OSA patients have a higher relative risk of sudden death from cardiac causes between midnight and 6 am compared to other times, contrasting with the general population, which has a nadir of sudden death risk during this period.

Question 34

How variable is the severity of excessive daytime sleepiness (EDS) in OSA?

Answer 34

EDS severity is highly variable. Chronic sleep deprivation and fragmentation from respiratory events are believed to cause sleepiness, though hypoxemia may also play a role. No clear PSG variable explains EDS, and correlations between sleep fragmentation and cognitive functioning or EDS are modest.

Question 35

How does OSA contribute to neurocognitive dysfunction?

Answer 35

OSA can lead to neurocognitive dysfunction through chronic sleep deprivation and fragmentation, affecting cognitive functioning and daytime alertness. EEG may not detect all adverse effects of respiratory disturbances, as noncortical arousals or periods of airflow limitation can contribute to symptoms.

Question 36

How do factors beyond OSA contribute to EDS?

Answer 36

Insufficient sleep, medication side effects, and individual variability in tolerating sleep fragmentation contribute to EDS, resulting in modest correlations between AHI and subjective or objective measures.

Question 37

How does OSA impact automobile accidents?

Answer 37

Studies show a 2-3x increased risk of accidents for untreated OSA patients. The presence of OSA and a history of previous accidents or frequent drowsiness at the wheel identify high-risk individuals.

Question 38

How can driving impairment in OSA patients be assessed and what does it show?

Answer 38

Objective tests for driving impairment are limited, but MWT and MSLT could be used. Studies show MWT mean sleep latency less than 19 minutes associates with driving simulator impairment, with very sleepy patients showing more line crossings than mildly sleepy ones.

Question 39

How does CPAP treatment affect driving in OSA patients?

Answer 39

CPAP treatment improves performance on driving simulators and seems to reduce traffic accidents.

Question 40

How does OSA affect nocturnal blood pressure?

Answer 40

20-40% of OSA patients fail to show a nocturnal dip in blood pressure. During obstructive apnea, blood pressure rises slightly, then increases abruptly at apnea termination due to arousal and sympathetic activation, with parasympathetic withdrawal

Question 41

What is the relationship between OSA and daytime hypertension?

Answer 41

There is controversy over whether OSA causes daytime hypertension. The Sleep Heart Health Study found an increased risk of self-reported hypertension with OSA, and an increase in AHI predicted the development of hypertension in 4 years, even after adjusting for obesity, age, and smoking.

Question 42

How does OSA impact cardiovascular function and treatment efficacy?

Answer 42

OSA may worsen physiological impacts or impair treatment efficacy for daytime hypertension. Nondippers with greater LV hypertrophy show increased mortality, and CPAP treatment can lower both nocturnal and daytime blood pressure by about 10 mm Hg.

Question 43

How does CPAP therapy impact blood pressure in OSA patients?

Answer 43

CPAP reduces 24-hour blood pressure by about 2 mm Hg, with greater reductions in severe OSA patients using CPAP regularly. Some studies found no or minimal change in daytime blood pressure.

Question 44

How does OSA contribute to pulmonary hypertension?

Answer 44

Both hypoxemia and acidosis constrict pulmonary arteries, leading to pulmonary hypertension episodes during apnea. Pulmonary pressures usually normalize if PaO2 is normal in the daytime, but COPD or LV diastolic dysfunction increases prevalence and severity.

Question 45

How prevalent is pulmonary hypertension in OSA patients?

Answer 45

Pulmonary hypertension incidence in OSA patients is estimated at 20-40%. CPAP treatment improves pulmonary hypertension.

Question 46

How do arrhythmias in OSA patients manifest?

Answer 46

Heart rate cycles, slowing with apnea onset, fluctuating during apnea, and increasing post-apnea. Vagal tone increases during apnea from hypoxic stimulation, and then tachycardia follows with resumption of breathing. 48% of OSA patients have arrhythmias.

Question 47

How does CPAP therapy affect arrhythmias?

Answer 47

CPAP dramatically improves arrhythmias, and heart rate variability increases after treatment, indicating reduced sympathetic activity.

Question 48

What factors are associated with atrial fibrillation in OSA patients?

Answer 48

Atrial fibrillation correlates with obesity and arterial O2 desaturation more than AHI. Untreated OSA worsens arrhythmia control.

Question 49

How does OSA affect coronary artery disease (CAD)?

Answer 49

OSA slightly increases the prevalence of self-reported CAD, increases CAD mortality in untreated OSA patients, and associates with an increased risk of incident CAD, particularly in men younger than 70 years, with stronger associations for severe OSA.

Question 50

How does OSA contribute to atherosclerosis and thrombosis?

Answer 50

OSA raises early morning hematocrit and fibrinogen levels, which decrease with CPAP treatment. VEGF, neutrophil, and platelet activation also decrease, while inflammation, marked by C-reactive protein, is reduced by CPAP. Intermittent hypoxia activates inflammatory pathways, elevating TNF-alpha and IL-8, which decrease with CPAP.

Question 51

How does CPAP therapy affect inflammatory changes in OSA patients?

Answer 51

CPAP treatment reduces several inflammatory markers, including C-reactive protein, TNF-alpha, and IL-8, though these results need confirmation through controlled trials. A study found decreases in C-reactive protein with good CPAP compliance and high baseline levels.

Question 52

What is the relationship between OSA and congestive heart failure (CHF)?

Answer 52

OSA increases the risk of CHF, and sleep-disordered breathing is common in CHF patients. In CHF patients, OSA's negative intrathoracic pressure, hypoxemia, and increased sympathetic tone impair ventricular function.

Question 53

How does CPAP therapy affect CHF patients with OSA?

Answer 53

CPAP treatment improves ejection fraction and symptoms in CHF patients, likely by reducing sympathetic tone and ventricular afterload, though no study confirms reduced mortality.

Question 54

How does OSA impact cerebrovascular accidents (CVA)?

Answer 54

OSA prevalence is high after CVA. CSB-CSA may resolve early post-CVA, while OSA persists. Studies show an increased CVA risk with OSA, potentially due to atherosclerosis, hypertension, and morning hemoconcentration.

Question 55

How does OSA affect cerebral perfusion?

Answer 55

OSA raises intracranial pressure (ICP) and reduces cerebral blood flow, with ICP increases correlating with apnea length. ICP rises from central venous pressure, systemic pressure, and cerebral vasodilatation from PaCO2 increases.

Question 56

How does OSA impact CVA recovery?

Answer 56

The Barthel index is lower in OSA patients post-CVA, and CPAP treatment reduces mortality, though adherence to CPAP in recent CVA patients is low.

Question 57

What is the association between erectile dysfunction and sleep disorders?

Answer 57

There appears to be a link between erectile dysfunction and sleep disorders, supported by survey studies and small case series. CPAP treatment seems beneficial.

Question 58

How does OSA associate with diabetes?

Answer 58

OSA is associated with impaired insulin sensitivity, glucose effectiveness, and pancreatic beta cell function, independent of adiposity. CPAP improves insulin sensitivity, particularly in non-obese patients.

Question 59

How does CPAP therapy affect insulin sensitivity?

Answer 59

CPAP therapy improves insulin sensitivity in non-diabetic males, and this effect is maintained over 12 weeks in moderately obese patients, though not always consistently.

Question 60

How does OSA contribute to nocturia?

Answer 60

OSA patients often report fewer awakenings to urinate after starting CPAP therapy. OSA has a high incidence of nocturnal urination (≥2 times a night), with age, arousal index, AHI, and oxygenation measures predicting nocturia.

Question 61

How does CPAP therapy affect nocturia in OSA patients?

Answer 61

CPAP therapy reduces sodium excretion, urinary flow, and chloride excretion. Atrial stretch from sleep apnea induces atrial natriuretic peptide release, causing increased sodium excretion.

Question 62

How does OSA impact children's neurobehavioral function?

Answer 62

OSA can cause hyperactivity and inattentiveness in children, with treatment often improving these symptoms. OSA may be misdiagnosed as ADHD, and both hypoxia and sleep fragmentation contribute to neurocognitive changes.

Question 63

How does OSA impact children's growth?

Answer 63

OSA can cause failure to thrive, potentially from reduced IGF and growth hormone secretion. Growth improves with treatment. OSA is also associated with obesity and inflammatory markers like leukotrienes.

Question 64

How does OSA affect cardiovascular health in children?

Answer 64

OSA causes similar cardiovascular consequences as in adults, with changes occurring at lower AHI values. Severe OSA (AHI > 10/hr) can cause nondipping blood pressure and high morning BP, with RV and LV hypertrophy in severe cases.

Question 65

What are the two main causes from sleep apnea that lead to downstream effects?

Answer 65

Protective arousal responses (sleep fragmentation, sleepiness) Repetitive hypoxia (oxidative stress, inflammation)

Question 66

What is oxidative stress?

Answer 66

When reduced oxygen is responded to, this induces oxidative stress. The production of oxygen free radicals, leading to damage and chronic inflammation

Question 67

How does blood pressure respond in an apnea?

Answer 67

BP decreases during apnea and increases in recovery

Question 68

What does the blood pressure changes during apneas lead to?

Answer 68

Repeated vascular strain as some people can have 100s of events a night. The blood pressure changes can be very large for some people.

Question 69

What are the main three symptoms of sleep apnea?

Answer 69

1. Snoring 2. Witnessed apnea 3. Excessive daytime sleepiness The absence of these does not equate to absent SDB

Question 70

When considering the main three symptoms of sleep apnea, what should be completed to appropriately suggest further evaluation?

Answer 70

Go through each symptom categorically. snoring + witnessed apnea: if they live alone, they may not know. EDS: have to seek this out with a scale, very often people don't know the difference between fatigue and sleepiness or they have built up tolerance.

Question 71

What is the difference between fatigue and sleepiness?

Answer 71

Sleepiness: do you fall asleep under X circumstance Fatigue: tired

Question 72

How easy is it to diagnose sleep apnea and its severity?

Answer 72

Sleep apnea: not difficult, but do need to consider a variety of clinical settings, not just obese middle aged man. Severity of SA: not easy

Question 73

What are some clinical symptoms someone may present with that could be sleep apnea?

Answer 73

- snoring, witnessed apnea, EDS - unrestorative sleep, insomnia - cognitive deficits - headache - nocturia - reflux - impotence - many others

Question 74

What diseases does obstructive sleep apnea occur in more than 50% of?

Answer 74

- obesity - hypercapnia respiratory failure - diabetes type 2 - heart failure - hypertension - cardiac arrhythmias - myocardial infarction - stroke

Question 75

What is the correct clinical question to ask about sleep apnea when seeing someone with cardiac arrhythmias?

Answer 75

How much apnea, not is it there. Especially with atrial fibrillation.

Question 76

Which diseases is obstructive sleep apnea an independent risk factor for?

Answer 76

Cardiovascular disease - Systemic hypertension - Myocardial infarction - Stroke - Atherosclerosis - Cardiac arrhythmias - Heart failure

Question 77

What is the relationship between sleep apnea and cardiovascular events (fatal and non-fatal)?

Answer 77

Untreated severe sleep apnea is a major risk factor for cardiac events. Fatal: 15% of untreated severe OSA died of heart attack, similar amounts when treated with CPAP to mild OSA. Non-fatal: 30% of people with untreated severe OSA had some event. When treated, similar to controls

Question 78

What is the problem when diagnosing people with severe OSA clinically?

Answer 78

They have had symptoms for years so they may be vague about their symptoms as the development has been so long.

Question 79

What are some clinical effects from snoring?

Answer 79

All snoring is significant. In a patient with transient ischaemic attack, may induce unstable blood pressure swings. Heavy snoring with partial obstruction in COPD leads to hypercapnia respiratory failure. Snoring in pregnancy leads to hypertension.

Question 80

What happens in pregnancy in relation to snoring?

Answer 80

30% develop snoring in 3rd trimester. Risk factor for hypertension and diabetes.

Question 81

What populations need to be evaluated for OSA?

Answer 81

High risk subjects: - habitual snorers (at least 30% of population) - overweight/obese - hypertension -> all vascular disease - somnolence (sleepiness) Therefore at least 18% of males and 8% of females could need assessment

Question 82

What percentage of the population are habitual snorers?

Answer 82

30%

Question 83

What are the major problems with being able to diagnose OSA at the level we need to be?

Answer 83

There's a huge need to test people but, - Limited PSG access - - Required number of PSG exceed capacity by a factor of 10 in US and 50 in UK. - Need to change from diagnostic to other tests

Question 84

What proportion of people with moderate OSA have not been diagnosed based on the WSCS?

Answer 84

82% of males and 93% of females

Question 85

In the US, based on the incidence of OSA, how many PSGs do we need based on the population?

Answer 85

Incidence of AHI > 15 is at least 0.6% Therefore need 600 PSG per 100K population based on incidence alone.