Obstructive Sleep Apnea

• Obesity — the single most important modifiable risk factor ^[1][2]
  • Fat deposits in the parapharyngeal space and tongue base → ↑ soft tissue weight pressing on the airway
  • Central/truncal obesity also ↓ lung volumes → ↓ tracheal tug (caudal traction on the pharynx) → ↑ collapsibility
  • BMI > 30 kg/m² is strongly associated; neck circumference > 40 cm (16 inches) is a particularly strong predictor ^[1]
• Craniofacial factors: ^[2]
  • Micrognathia / retrognathia (undersized or recessed jaw) → posterior displacement of the tongue base
  • Macroglossia — the tongue is too large for the oral cavity, falls back in supine position
  • Adenotonsillar hypertrophy — the most important factor in children (because their airways are already small) ^[3]
  • Nasal obstruction (deviated septum, polyps, turbinate hypertrophy)
  • Redundant pharyngeal tissues due to fatty infiltration ^[3]
• Mallampati score: higher score (III/IV) correlates with more crowded oropharynx and ↑ OSA risk ^[2]

• Male sex (or post-menopausal women) ^[2]
  • Testosterone promotes fat deposition in the neck; progesterone (a respiratory stimulant) is lost after menopause
• Increasing age — loss of pharyngeal muscle tone, ↑ soft tissue laxity
• Ethnicity — in East Asian populations (including Hong Kong Chinese), craniofacial anatomy (e.g. smaller mandible, flatter midface) means OSA can occur at lower BMIs compared to Caucasians

• Alcohol — relaxes pharyngeal muscles, ↑ upper airway collapsibility, suppresses arousal response ^[2][3]
• Smoking — causes upper airway inflammation and oedema → narrowing
• Sedatives / muscle relaxants / opioids — same mechanism as alcohol
• Supine sleeping position — gravity pulls tongue and soft palate posteriorly

• Acromegaly — macroglossia and mucosal hypertrophy of the oropharyngeal tissues → OSA (~50% of acromegalics) ^[7][8]
• Hypothyroidism — myxoedema of upper airway soft tissues + ↓ ventilatory drive + weight gain ^[2]
• Down syndrome — midface hypoplasia, macroglossia, hypotonia → very high prevalence of OSA in children ^[2]

• Familial predisposition — relatives of OSA patients have 2–4× increased risk (shared craniofacial anatomy and body habitus) ^[2]
• Down syndrome, Marfan syndrome, Pierre Robin sequence ^[2]

The upper airway from nose to larynx can be divided into:

1. Nasopharynx (posterior to nasal cavity, above soft palate)
2. Oropharynx (behind the oral cavity, between soft palate and epiglottis) — this is where most obstruction occurs in OSA
3. Hypopharynx/Laryngopharynx (from epiglottis to laryngeal inlet)

The pharynx is a collapsible muscular tube — unlike the trachea which has cartilaginous rings holding it open, the pharynx relies entirely on dilator muscle tone to maintain patency. The key dilator muscle is the genioglossus (which protrudes the tongue forward and pulls the base of the tongue off the posterior pharyngeal wall).

• Sleep occurs in cycles of NREM (Non-Rapid Eye Movement) stages 1-3 and REM (Rapid Eye Movement) sleep
• During sleep:
  • Ventilatory drive drops → decreased responsiveness to hypoxia and hypercapnia ^[3]
  • Neuromuscular tone of the upper airway decreases — particularly during REM sleep (skeletal muscle atonia) ^[3]
  • These are normal physiological changes; in a person with normal airway geometry, the airway stays open despite reduced tone

The process ^[3]:

This cycle repeats hundreds of times per night in severe OSA — the patient may never reach deep restorative sleep.

1. Intermittent Hypoxia (IH)

• Each apnoeic episode causes a drop in SpO₂ (desaturation), followed by reoxygenation upon arousal
• This repetitive hypoxia–reoxygenation cycle is analogous to ischaemia-reperfusion injury and generates:
  • Reactive oxygen species (ROS) → oxidative stress
  • Sympathetic activation → sustained ↑ in catecholamines → systemic hypertension (even during the daytime)
  • Endothelial dysfunction → accelerated atherosclerosis
  • Systemic inflammation (↑ CRP, TNF-α, IL-6) → promotes insulin resistance, metabolic syndrome
  • ↑ Atrial natriuretic peptide (ANP) release from hypoxia-induced atrial stretch → nocturia ^[2]
  • Pulmonary vasoconstriction (hypoxic pulmonary vasoconstriction) → if chronic and severe → pulmonary hypertension → cor pulmonale ^[2]
  • Polycythaemia — chronic intermittent hypoxia stimulates EPO production ^[2]

2. Sleep Fragmentation

• Recurrent arousals prevent progression to deep (N3) and REM sleep
• This causes:
  • Excessive daytime sleepiness (EDS) — the cardinal daytime symptom
  • Cognitive impairment — poor concentration, memory deficits
  • Mood disturbance — irritability, depression
  • Morning headache — from a combination of CO₂ retention and sleep deprivation

• The vast majority of adult OSA is multifactorial, with obesity + anatomical predisposition as the dominant contributors
• In Hong Kong's Chinese population, craniofacial factors play a proportionally larger role compared to Western populations — OSA occurs at lower BMIs due to smaller mandibular size and midface dimensions
• Despite this, obesity rates are rising in HK (prevalence of obesity ~20% in adults), driving increasing OSA prevalence

• Positional OSA: AHI is ≥ 2× higher in the supine position compared to lateral — relevant because positional therapy (avoiding supine sleep) can be a treatment option for supine-isolated OSA ^[9]
• Non-positional OSA: AHI is elevated regardless of position

• REM-related OSA: events predominantly during REM sleep (when muscle atonia is most pronounced)
• More common in women and younger patients; may indicate milder disease if overall AHI is only mildly elevated

• A validated self-administered questionnaire measuring subjective daytime sleepiness
• Rates the likelihood of dozing off in 8 everyday situations (e.g. watching TV, sitting in traffic, reading) on a scale of 0–3 each
• Total score 0–24
• ESS ≥ 10 suggests significant excessive daytime sleepiness and warrants referral for sleep study ^[2]

• A validated screening tool for OSA, especially used in pre-operative assessment
• 8 yes/no questions:
  • Snoring — Do you snore loudly?
  • Tired — Do you feel tired/sleepy during the day?
  • Observed — Has anyone observed you stop breathing during sleep?
  • Pressure — Do you have high blood pressure?
  • BMI — BMI > 35?
  • Age — Age > 50?
  • Neck — Neck circumference > 40 cm?
  • Gender — Male?
• Score ≥ 5 → high risk, refer for sleep study ^[2]
• Score 3–4 = intermediate risk; score 0–2 = low risk

• Cardiovascular: HTN (most well-established — OSA is the commonest identifiable cause of resistant HTN), DM (insulin resistance from sympathetic activation and intermittent hypoxia), HF, arrhythmia (especially AF), stroke, coronary artery disease
• Hypoxia-related: polycythaemia, pulmonary hypertension, glaucoma (increased vascular resistance) ^[2]
• Metabolic syndrome: OSA is an independent risk factor, bidirectional relationship with obesity

• Excessive daytime sleepiness
• Poor concentration
• Depression and anxiety
• Cognitive decline

• Sleepiness-related accidents ^[2] — motor vehicle accidents (2–7× increased risk), occupational injuries
  • This is a public safety issue — occupation and driving status should always be assessed ^[5]
• Impaired work performance
• Relationship strain (bed partner disturbed by snoring)

• OSA causes nocturia through difficulty with sleep maintenance and loss of diurnal variation in release of vasopressin (ADH) ^[10]
• Also through hypoxia-induced ↑ ANP → natriuresis ^[2]

• OSA → daytime sleepiness, occupation — always ask about these when evaluating secondary causes of hypertension ^[5]
• Investigation: polysomnography ^[5][6]
• OSA is a recognised cause of resistant hypertension — if a patient's BP is not controlled on 3 antihypertensives at optimal doses, think OSA

• OSA is listed as a secondary cause of enuresis in children ^[4]
• Mechanism: defective sleep arousal + ANP-mediated polyuria

• ~50% of acromegaly patients have OSA ^[8]
• Macroglossia and mucosal hypertrophy of the oropharyngeal tissues directly cause obstruction ^[7][8]

• Obstructive sleep apnea: difficulty with sleep maintenance and loss of diurnal variation in release of vasopressin (ADH) ^[10]

• The most common cause of EDS in the general population — and the first thing to exclude ^[3][11]
• Mechanism: simply not enough hours in bed (social, occupational, voluntary reasons)
• Distinguishing features: No snoring, no witnessed apnoeas. The patient acknowledges they don't get enough sleep. Sleep diary reveals < 7 hours/night. Correcting sleep duration resolves symptoms
• Why it matters: Many patients referred for "OSA workup" are actually just sleep-deprived. Always take a thorough sleep history before jumping to polysomnography

• Apnoea without ventilatory effort (no arousal) ^[2] — contrast with OSA where there IS effort but no flow
• Defect in central (↓ ventilatory drive) or peripheral (↓ muscle contraction) ^[3]
• Causes: central neurological lesions, neuropathies, NMJ disease, muscle diseases ^[3]; also CHF (Cheyne-Stokes respiration) ^[2]
• Distinguishing features: Bed partner may note absence of chest/abdominal movement during apnoeic episodes (vs. OSA where the chest heaves but no air gets through). Typically less snoring than OSA. Often a/w underlying neurological or cardiac disease. Diagnosed on polysomnography by absence of respiratory effort during apnoeas
• Why it's important: Treatment differs — CPAP may worsen some forms of CSA (particularly in CHF). Adaptive servo-ventilation (ASV) is used instead for some CSA subtypes, though it is contraindicated in HFrEF with EF < 45%

• The "Pickwickian syndrome" — BMI ≥ 30 + chronic daytime hypercapnia (PaCO₂ > 45 mmHg) + sleep-disordered breathing, in the absence of other causes of hypoventilation ^[12]
• ~90% of OHS patients have concurrent OSA, so there is massive overlap ^[1]
• Distinguishing features: The key differentiator is daytime hypercapnia — in pure OSA, PaCO₂ normalises during wakefulness. In OHS, the CO₂ stays elevated even when the patient is awake. ABG showing daytime type 2 respiratory failure (↑ PaCO₂, ↑ HCO₃⁻) clinches the diagnosis
• Respiratory diseases attributable to obesity: breathlessness, obstructive sleep apnoea, hypoventilation (Pickwickian syndrome / obesity hypoventilation syndrome) ^[12]
• Why the distinction matters: OHS often requires bilevel PAP (BiPAP) rather than simple CPAP, because these patients need both PEEP (to splint the airway) AND pressure support (to augment tidal volume and blow off CO₂)

• Excessive daytime sleepiness with cataplexy, hypnagogic hallucination and sleep paralysis ^[11]
• "Narcolepsy" from Greek: narke = numbness/stupor, lepsis = seizure — a "seizure of sleep"
• Mechanism: loss of hypocretin/orexin-producing neurons in the lateral hypothalamus (autoimmune in type 1)
• Tetrad: EDS + cataplexy (sudden loss of muscle tone triggered by emotions like laughter) + sleep paralysis + hypnagogic/hypnopompic hallucinations
• Distinguishing features: The sleep attacks are irresistible and occur during active situations (not just sedentary). Cataplexy is pathognomonic when present. No snoring or apnoeas. Diagnosis requires multiple sleep latency test (MSLT) showing mean sleep latency < 8 min + ≥ 2 sleep-onset REM periods (SOREMPs)
• Why to consider: A young patient with EDS and no obesity/snoring should raise suspicion for narcolepsy

• Periodic limb movement syndrome — involuntary repetitive movements (typically dorsiflexion of foot/toe) during sleep causing arousals ^[3]
• Restless leg syndrome: urge to move legs + unpleasant leg sensation when sitting/lying down ^[13]
• Distinguishing features: Partner may report Hx of restless sleep or even limb movement/muscle twitches during sleep ^[13]. The key symptom is the urge to move and the unpleasant sensory component in the legs, which is relieved by movement. No snoring, no apnoeas
• Important overlap: RLS/PLMD can coexist with OSA and compound the sleep fragmentation

• Can produce both insomnia (early-morning awakening) and hypersomnia ^[13]
• Distinguishing features: Screen for low mood, anhedonia, guilt, worthlessness, suicidal ideation. Fatigue is more prominent than true sleepiness. No nocturnal respiratory symptoms. PHQ-9 or other screening tools
• Bidirectional relationship: OSA and depression commonly coexist — chronic sleep fragmentation can cause depressive symptoms, and untreated depression can worsen perceived sleep quality

• Causes both EDS (from ↓ metabolic rate and central effects) and can cause/exacerbate OSA (myxoedematous infiltration of upper airway tissues + weight gain + ↓ ventilatory drive) ^[2]
• Distinguishing features: Look for cold intolerance, weight gain, constipation, dry skin, bradycardia, delayed relaxation of reflexes. Check TSH
• Why it matters: Treating the hypothyroidism may improve or resolve the OSA

• Ask for medication use, including Over the Counter meds ^[1]
• Sedatives, benzodiazepines, opioids, antihistamines, antipsychotics, antiepileptics can all cause EDS
• Distinguishing features: Temporal relationship with drug initiation. Resolution with dose reduction/cessation
• Serotonergic antidepressants can also cause or precipitate REM sleep behaviour disorder ^[14]

• Chronic widespread pain + fatigue + unrefreshing sleep
• Distinguishing features: Prominent pain complaints, multiple tender points, no respiratory symptoms

• Rare — excessive sleepiness despite adequate and undisturbed sleep, with prolonged and unrefreshing naps (contrast with narcolepsy where naps are short and refreshing)
• Diagnosis of exclusion after ruling out OSA, insufficient sleep, narcolepsy, depression, drugs

When taking a history for secondary hypertension, you ask for snoring, daytime somnolence, obesity — you are suspecting obstructive sleep apnoea ^[6]

The differential of secondary hypertension includes ^[5][6]:

Investigation for OSA in the hypertension workup: polysomnography ^[5]

OSA is a differential diagnosis of nocturia ^[10]:

Secondary polycythaemia (EPO-mediated) must be excluded before diagnosing polycythaemia vera ^[15]:

• Compensatory EPO secretion due to hypoxia: COPD, cyanotic heart disease — and OSA (chronic intermittent hypoxia → ↑ EPO → ↑ RBC mass) ^[15]
• Distinguished from PV by the presence of an elevated EPO level (PV has low EPO + JAK2 mutation)

• OSA is an independent risk factor for AF — intermittent hypoxia causes atrial stretch, autonomic surges, and atrial electrical remodelling
• Always screen for OSA in patients with AF, especially if obese, snoring, or with resistant AF despite treatment

• Hypoxia: polycythaemia, pulmonary hypertension, glaucoma (increased vascular resistance) ^[2]
• OSA is associated with normal-tension glaucoma and floppy eyelid syndrome — mechanism is intermittent hypoxia → vascular dysregulation → optic nerve ischaemia

Diagnosis of OSA is based upon presence or absence of related symptoms + frequency of respiratory events during sleep as measured by polysomnography or home sleep apnea testing (HSAT) ^[11]

First, let's be precise about the event definitions — these are the building blocks:

Now, the indices used to quantify severity:

Classification for diagnosis and severity of OSA (Adults) ^[1]:

In children, AHI > 1 is considered abnormal ^[3]

Why these thresholds? They are somewhat arbitrary but based on epidemiological data linking specific AHI ranges to increasing cardiovascular risk, neurocognitive impairment, and accident risk. The clinical significance increases steeply above AHI 15, and above AHI 30 the risk of cardiovascular events, resistant HTN, and motor vehicle accidents is markedly elevated.

Home sleep study: only SpO₂ ± video ^[2]

• Also known as Level 3 or Level 4 portable monitoring
• Typically measures: nasal airflow, chest/abdominal effort, SpO₂, body position, ± heart rate
• Does NOT include EEG — so it cannot formally score sleep stages or calculate true "sleep time" (uses recording time instead)

Advantages:

• More convenient, cheaper, done in the patient's own sleeping environment (more natural sleep)
• Adequate for diagnosing moderate-to-severe OSA in patients with high pre-test probability

Limitations:

• Underestimates AHI — because it divides events by recording time (not sleep time); if the patient is awake for part of the recording, the denominator is inflated
• Cannot detect RERAs, PLMD, or sleep architecture abnormalities
• Cannot reliably distinguish obstructive from central apnoea (no effort channels in the simplest devices)
• Not appropriate for: patients with significant comorbidities (CHF, COPD, neuromuscular disease), suspected CSA, or when initial HSAT is negative but clinical suspicion remains high — these patients need in-lab PSG

Drug-induced sleep endoscopy (DISE): VOTE classification (velum, oropharynx, tongue base, epiglottis) ^[2]

• What it is: Flexible nasendoscopy performed while the patient is in a pharmacologically induced state of sleep (using propofol or midazolam)
• Why it's done: To directly visualise the site and pattern of upper airway collapse in real-time
• VOTE classification: Grades the degree and configuration of obstruction at each level:
  • V = Velum (soft palate / uvula)
  • O = Oropharyngeal lateral walls (tonsils, pharyngeal walls)
  • T = Tongue base
  • E = Epiglottis
• Each site is graded as 0 (no obstruction), 1 (partial), or 2 (complete), and the pattern of collapse is noted (anteroposterior, lateral, or concentric)
• When it's used: Primarily for surgical planning — if a patient has failed CPAP and is being considered for surgical intervention (e.g. uvulopalatopharyngoplasty, tongue base surgery), DISE identifies which level(s) to target
• Not a diagnostic test for OSA itself — it is used after OSA is already confirmed

• The simplest form of "sleep study" — records only SpO₂ overnight
• Can detect repetitive desaturation-reoxygenation cycles ("saw-tooth" pattern) suggestive of sleep apnoea
• Useful as a screening tool when full PSG or HSAT is not available
• Limitation: Cannot determine AHI, cannot distinguish obstructive from central apnoea, high false-negative rate in mild OSA (where desaturations may be minimal)

Investigations targeting different differentials ^[5]:

• Cushing's: 9am morning cortisol → followed up by suppression tests
• Acromegaly: IGF-1 levels
• Obesity / OSA: Polysomnography
• Renovascular causes: Ultrasound + doppler

• Cardiovascular: HT ^[2]
• Complications: HTN, ischaemic heart disease, DM ^[3]
• Other diseases: Hypertension, diabetes mellitus, stroke, coronary artery disease ^[1]

Mechanism: Intermittent hypoxia → tonic sympathetic activation (not just during sleep — the sympathetic overdrive persists into the daytime) → sustained ↑ in circulating catecholamines → peripheral vasoconstriction → ↑ systemic vascular resistance → HTN. Additionally, endothelial dysfunction impairs nitric oxide (NO)-mediated vasodilation, and activation of the renin-angiotensin-aldosterone system (RAAS) further compounds the hypertensive effect.

Clinical significance:

• OSA → daytime sleepiness, occupation — always ask about these when evaluating secondary hypertension ^[5]
• OSA is the most common identifiable cause of resistant hypertension (defined as BP uncontrolled on ≥ 3 agents at optimal doses including a diuretic)
• Characteristically produces a non-dipping BP pattern on 24-hour ambulatory BP monitoring — normally BP dips by ≥ 10% at night; in OSA, the repeated sympathetic surges from apnoeas abolish this nocturnal dip
• HTN is well-demonstrated to be a result of OSA ^[3] — the strongest evidence base of any cardiovascular complication

Footnote from Ryan Ho Respiratory ^[3]: "HTN is well-demonstrated to be a result of OSA, whereas in the other two (IHD and DM) the evidence is less well-established." This nuance is important for exam answers — don't equate the strength of evidence for all cardiovascular complications.

• Coronary artery disease (CAD) ^[11]

Mechanism: Multiple synergistic pathways:

• Chronic intermittent hypoxia → ROS → oxidised LDL → endothelial dysfunction → accelerated atherosclerosis
• Systemic inflammation (↑ CRP, TNF-α, IL-6) → plaque instability
• Sympathetic activation → ↑ heart rate, ↑ BP → ↑ myocardial oxygen demand
• Nocturnal hypoxia → direct myocardial ischaemia in patients with pre-existing coronary stenosis

Clinical features: Nocturnal angina is a recognised complication of OSA — episodes of chest pain during sleep corresponding to oxygen desaturations. This is an indication for urgent CPAP ^[3][11].

• Arrhythmia ^[2]
• Cardiac arrhythmia ^[11]:
  • Bradycardia (OSA)
  • Sinus pause (OSA)
  • Atrial fibrillation (CSA) ^[11]

Mechanism: The "diving reflex" analogy helps explain the arrhythmia pattern:

• During apnoea: hypoxia activates a vagal (parasympathetic) reflex → bradycardia, sinus pauses, AV block — this is the body's attempt to conserve oxygen (similar to the mammalian diving reflex)
• During the arousal/recovery phase: sudden sympathetic surge → tachycardia, ectopic beats
• This creates a characteristic cyclical bradycardia-tachycardia pattern on Holter monitoring that is virtually pathognomonic for OSA
• Atrial stretch from the highly negative intrathoracic pressure + intermittent hypoxia + autonomic surges → atrial electrical remodelling → atrial fibrillation
• AF prevalence in severe OSA is ~4–5× that of the general population

Clinical implication: Recurrent nocturnal AF or unexplained bradycardia in an obese patient should prompt OSA screening.

• HF ^[2]
• CVS: AF, heart failure (cor pulmonale), pulmonary hypertension ^[2]

Mechanism — two pathways to HF:

Left heart failure:

• Chronic ↑ afterload from HTN → LV hypertrophy → eventually LV systolic and/or diastolic dysfunction
• Highly negative intrathoracic pressure during obstructive apnoeas → ↑ LV transmural pressure → ↑ afterload → impaired LV ejection
• Sympathetic activation → neurohormonal activation (RAAS, endothelin) → myocardial remodelling

Right heart failure (cor pulmonale):

• Chronic intermittent hypoxia → hypoxic pulmonary vasoconstriction → if prolonged and severe → pulmonary hypertension → RV pressure overload → RV dilatation and failure
• This leads to the classic signs: ↑ JVP, peripheral oedema, hepatomegaly, ascites (from hydrostatic back-pressure in the hepatic veins)
• Cor pulmonale is rare except in presence of other conditions, e.g. OHS, COPD ^[3] — pure OSA rarely causes cor pulmonale on its own because the hypoxia is intermittent, not sustained. It is when OSA overlaps with OHS or COPD (the "overlap syndrome") that chronic hypoxaemia becomes severe enough to drive sustained pulmonary hypertension

• Stroke ^[2][11]
• Neuro: stroke ^[2]

Mechanism: Multifactorial:

• HTN (the single strongest modifiable risk factor for stroke) — directly caused by OSA
• Accelerated atherosclerosis of cerebral and carotid arteries
• AF (a complication of OSA) → cardioembolic stroke
• Nocturnal hypotension during severe apnoeas → watershed cerebral ischaemia
• Paradoxical embolism through patent foramen ovale (PFO) during apnoea-related right-to-left shunting (raised intrathoracic pressure)
• Hypercoagulability from sympathetic activation and systemic inflammation

• Pulmonary hypertension ^[2]
• Hypoxia: polycythaemia, pulmonary hypertension, glaucoma (increased vascular resistance) ^[2]

Mechanism: Alveolar hypoxia during apnoeas triggers hypoxic pulmonary vasoconstriction (HPV) — a physiological reflex designed to divert blood away from poorly ventilated lung units. In OSA, this reflex fires repeatedly throughout the night. Over months to years, the chronic repetitive vasoconstriction leads to pulmonary vascular remodelling (muscular hypertrophy of pulmonary arterioles, intimal proliferation), resulting in fixed pulmonary hypertension that persists even during the daytime.

This falls under WHO Group 3 pulmonary hypertension (PH due to lung diseases and/or hypoxia).

• Type II DM and insulin resistance ^[11]
• DM ^[2]

Mechanism: Several pathways, all stemming from intermittent hypoxia and sleep fragmentation:

• Sympathetic activation → ↑ catecholamines → ↑ hepatic glucose output, ↓ insulin sensitivity in skeletal muscle
• Systemic inflammation (TNF-α, IL-6) → impaired insulin signalling (phosphorylation of IRS-1 at inhibitory serine residues)
• Sleep fragmentation → disrupted GH and cortisol circadian rhythms → ↑ cortisol → insulin resistance
• ↓ Leptin sensitivity, ↑ ghrelin → ↑ appetite → weight gain → further insulin resistance (vicious cycle)

OSA is an independent risk factor for T2DM even after adjusting for BMI — meaning the intermittent hypoxia itself contributes, not just the obesity.

• Non-alcoholic fatty liver disease ^[11]

Mechanism: Intermittent hypoxia → hepatic oxidative stress + systemic inflammation → hepatocyte injury → steatosis, steatohepatitis, and potentially fibrosis. This is compounded by insulin resistance and obesity.

• OSA is independently associated with ↑ triglycerides, ↓ HDL, and features of metabolic syndrome
• The overlap of OSA + obesity + HTN + insulin resistance + dyslipidaemia constitutes "metabolic syndrome," and these conditions potentiate each other in a positive feedback loop

• Psychological: excessive daytime sleepiness, poor concentration ^[2]

Mechanism: Chronic sleep fragmentation prevents progression into restorative deep (N3) and REM sleep → impaired memory consolidation (hippocampus-dependent, occurs in N3/REM), ↓ sustained attention (prefrontal cortex), ↓ executive function. Chronic intermittent hypoxia may also cause hippocampal neuronal injury and grey matter volume loss in prefrontal regions, as shown on MRI volumetric studies.

Clinical features:

• Poor concentration and memory ^[2]
• Morning headache — from CO₂ retention (hypercapnia) causing cerebral vasodilation, compounded by sleep deprivation
• Impaired reaction time → risk of accidents (see below)

Mechanism: Sleep deprivation disrupts serotonergic and dopaminergic pathways in the prefrontal cortex and limbic system → emotional dysregulation, low mood, irritability. Chronic fatigue and social consequences of OSA (relationship strain, impaired work performance) further contribute.

Bidirectional relationship: Depression can worsen sleep quality and reduce CPAP adherence, creating a vicious cycle.