Cardiovascular Consequences of Sleep Apnoea

Introduction

Pathophysiological Mechanisms Linking OSA to CVD

1. Systemic Hypertension

• OSA stimulates carotid body chemoreceptors during hypoxaemia → reflex sympathetic activation → peripheral vasoconstriction → elevated BP.
• Persistently elevated sympathetic tone causes vascular remodelling, making hypertension sustained even during wakefulness.
• Prevalence: ~50% of OSA patients have hypertension; ~30% of hypertensives have OSA.
• In non-obese individuals, OSA is the more likely cause of hypertension than obesity per se (Sleep Heart Health Study - BMI <27 kg/m²).
• OSA is the most common identifiable cause of resistant hypertension (prevalence 60-90% in resistant HTN patients).
• Fluid retention (aldosterone-mediated sodium retention) causes dependent oedema; rostral fluid shift in recumbency worsens pharyngeal oedema, creating a vicious cycle.
• CPAP effect: Modest reductions in systolic BP (~2-2.5 mmHg) in general hypertension; larger reductions (~5-7 mmHg systolic, 3-5 mmHg diastolic) in resistant hypertension with good CPAP adherence. CPAP also restores the normal nocturnal BP dipping pattern.

2. Coronary Heart Disease (CHD) and Myocardial Ischaemia

• Dual hit: OSA simultaneously increases myocardial oxygen demand (tachycardia, raised BP from sympathetic activity, cardiac hypertrophy) and decreases oxygen delivery (obstructed breathing, hypoxaemia).
• Large negative intrathoracic pressure swings (diaphragm contracting against closed airway) increase LV wall tension and afterload, worsening ischaemia.
• Vibration from snoring may cause direct damage to carotid artery walls, contributing to carotid atherosclerosis.
• Endothelial damage and reduced NO production impair coronary vasodilation.
• ST-segment depression on overnight ECGs confirms nocturnal myocardial ischaemia in OSA patients.
• Epidemiological data:
  • MESA cohort: physician-diagnosed sleep apnoea → 1.9x hazard ratio for incident cardiovascular events, 2.4x higher mortality.
  • Spanish cohort (5-10 years): untreated severe OSA → 2.9x fatal and 3.2x non-fatal cardiovascular events (men); 3.5x mortality (women).
  • Sleep Heart Health Study: AHI ≥15 → 35% increased CHD incidence over 8 years; 70% increased risk in men <70 years.
• Morning peak of MI onset is more common in OSA patients (temporal link supporting causality).
• Individuals with the most severe hypoxic burden (highest quintile) had ~2x risk of cardiovascular death.

3. Cardiac Arrhythmias

a) Atrial Fibrillation (AF)

• Most clinically significant arrhythmia associated with OSA.
• Mechanisms: atrial stretch from elevated pulmonary/systemic pressures; hypoxia-driven atrial remodelling; vagal surges (at apnoea end) slowing the sinus rate; sympathetic surges triggering ectopy.
• OSA patients have a 2-4x higher risk of AF.
• Recurrence after cardioversion or ablation is significantly higher without CPAP treatment.
• Paroxysmal nocturnal AF is a red flag for underlying OSA.

b) Bradyarrhythmias and Heart Block

• Vagal surges at the end of apnoea episodes can cause sinus pauses, sinoatrial block, and even second-degree AV block during sleep - these often resolve completely with CPAP.

c) Ventricular Arrhythmias

• Hypoxia + acidosis + QT prolongation create a substrate for ventricular ectopy and ventricular tachycardia, temporally correlated with apnoea episodes.
• Sudden cardiac death risk is increased; patients with OSA more commonly die between midnight and 6 AM (reversal of the normal morning peak pattern).

4. Heart Failure (HF)

OSA → HF

• Negative intrathoracic pressure swings increase LV transmural pressure and afterload → LV hypertrophy → diastolic dysfunction → HF with preserved ejection fraction (HFpEF).
• Recurrent hypoxaemia causes direct myocardial depression.
• Sympathetic activation increases systemic vascular resistance → pressure overload.

HF → OSA (bidirectional relationship)

• Fluid redistribution in HF (from legs to neck/pharynx in recumbency) narrows the upper airway, worsening OSA severity.
• Elevated left atrial pressure → pulmonary congestion → chemoreceptor sensitisation → periodic breathing.

Central Sleep Apnoea / Cheyne-Stokes Respiration in HF

• Common in HF with reduced ejection fraction (HFrEF): prevalence 30-50%.
• Characterised by crescendo-decrescendo breathing pattern with central apnoeas.
• Marker of worse prognosis; associated with increased sudden death risk.
• Treatment: CPAP, ASV (adaptive servoventilation - caution: ASV is contraindicated in HFrEF with LVEF ≤45% - SERVE-HF trial showed increased mortality).

5. Pulmonary Hypertension (PH)

• Repeated hypoxia causes hypoxic pulmonary vasoconstriction → pulmonary arterial remodelling → sustained pulmonary hypertension.
• OSA-related PH is usually mild to moderate (mean PAP 25-35 mmHg), but may progress with obesity or lung disease co-morbidities.
• Right ventricular pressure overload → RV hypertrophy → cor pulmonale.
• CPAP lowers pulmonary artery pressure in OSA patients.

6. Stroke and Transient Ischaemic Attack (TIA)

• Multiple embolic pathways:
  1. Carotid atherosclerosis (OSA-related) → thromboembolic stroke.
  2. OSA-induced AF → cardioembolic stroke.
  3. Patent foramen ovale (PFO) - higher prevalence in OSA → paradoxical cerebral embolism.
• Cyclic surges in BP + hypoxaemia + hypercapnia impair cerebral autoregulation.
• Wake-up stroke (stroke occurring during or just after sleep) is particularly associated with OSA.
• AHA/ASA Guideline: sleep study should be considered after ischaemic stroke or TIA given the very high prevalence of OSA in this population.
• Effective CPAP use is associated with improved cerebrovascular (but not always cardiac) outcomes in post-stroke patients.

7. Metabolic Cardiovascular Risk Amplification

• OSA promotes insulin resistance and type 2 diabetes mellitus via sympathetic activation and intermittent hypoxia → compounding cardiovascular risk.
• Dyslipidaemia: increased triglycerides, decreased HDL.
• Atherosclerosis acceleration: oxidative stress + inflammation → endothelial injury → foam cell formation → plaque progression.
• Gut microbiome dysbiosis from OSA produces pro-inflammatory cytokines → hypertension, insulin resistance, atherosclerosis (emerging evidence).

Summary Table - Cardiovascular Consequences of OSA

Treatment Impact on Cardiovascular Outcomes

• Reduces catecholamines, oxidative stress, and inflammatory biomarkers.
• Lowers BP (modestly overall, significantly in resistant HTN with good adherence).
• Reduces AF recurrence post-ablation/cardioversion.
• Improves nocturnal arrhythmias (bradyarrhythmias often fully resolve).
• Reduces pulmonary artery pressure.
• Associated with improved cerebrovascular outcomes in compliant patients.

Key Exam Points to Remember

1. OSA is the most common identifiable cause of resistant hypertension.
2. AF is the most important arrhythmia - CPAP reduces recurrence after ablation.
3. Sudden cardiac deaths in OSA cluster between midnight and 6 AM (opposite to normal population).
4. ASV is contraindicated in HFrEF (LVEF ≤45%) due to increased mortality (SERVE-HF trial).
5. Wake-up stroke should prompt a sleep study.
6. Mechanisms: hypoxia → oxidative stress → NF-κB → inflammation → endothelial dysfunction → atherosclerosis.
7. CPAP improves biomarkers and some outcomes, but RCT evidence for hard cardiovascular endpoints is mixed due to adherence issues.