Human physiology and pharmacology in diseases 1

Sleep apnoea as a cause of cardiovascular diseases

Definitions

Obstructive sleep apnoea (OSA)

OSA is a repetitive interruption of air flow for less than 10 seconds during sleep despite the
persisting respiratory effort due to anatomical narrowing or total collapse of the pharyngeal
air way leading to transient arousal from sleep for more than 10 seconds. (Parish and Somers,
2004, Somers et al., 2008b)

Partial collapse (>30% reduction of air flow and 4 % oxygen desaturation) is less sever type
of apnoea known as hypopnoea.(Somers et al., 2008b)

To describe the severity of sleep apnoea, Apnoea- Hypopnoea Index (AHI) is introduced;
AHI measures the total number of apnoeas and hypopnoeas per hours of sleep. AHI less than
5/hr are considered to be normal, 5 – 15 is mild, 15 – 30 moderate and more than 30 is a
severe case.(Parish and Somers, 2004)

Signs, symptoms and clinical presentations of OSA

OSA patients suffer of excessive daytime sleepiness and fatigue due to fragmented sleep
during the night.(Caples et al., 2005) Snoring, choking, dry sour mouth and morning
headache are the most notable signs of OSA patients.(Caples et al., 2005)

Pathophysiology

(Lopez-Jimenez et al., 2008, Somers et al., 2008b)

This figure shows the anatomical abnormalities in the pharyngeal airway, tissues posterior to the tongue are
enlarged and partially or completely collapse leading to occlusion of the upper airway.
In OSA patients, pharyngeal collapse happens in the uvula and soft palate structures posterior
to the tongue. This region is supported by little bony structures, thus it depends on the
muscular activities for support, what happens in OSA is that abnormal increase in uvular soft
tissues will anatomically decrease the upper air way, and increased airway resistance to air
flow. This depletion in ventilation rate will lead to hypoxia and hypercabnia, arousal from
sleep is vital for the recovery of ventilation. (Somers et al., 2008b)

During wakefulness muscles dilating activities maintain normal air flow due to the role of
mechanoreceptors in the larynx that respond reflexively to the negative intrathoracic pressure
by increasing the activity of dilator muscles in the pharynx. This reflex is controlled by
sympathetic nervous system during wakefulness. But at sleep, sympathetic activities
decreases progressively. (Somers et al., 2008b, Caples et al., 2005), (Lopez-Jimenez et al.,
2008, White, 2005)

(Narkiewicz et al., 1998)

This figure shows the Electrocardiogram (ECG), HR, BP, Sympathetic neurogram and respiration of normal
control vs. sever OSA patient during sleep. ECG, BP especially diastolic BP, Neurogram and respiration
readings of OSA patient are altered and tend to be more condense and irregular.

Effects of normal sleep

Sleep is divided into two major stages; the first is the transition state between wakefulness
and deep sleep and known as Rapid Eye Movement (REM) sleep and constitutes around 15%
of normal sleep.
The other stage is deep sleep and known as Non Rapid Eye Movement (NREM) sleep and
constitutes the bulk of normal sleep of around 85%.
In NREM sleep the cardiovascular system is in a state of relaxation. Heart Rate (HR),
Cardiac Output (CO), Blood Pressure (BP), sympathetic activities and systematic vascular
resistance decrease.(Caples et al., 2005, Bradley and Floras, 2003)

In OSA patients this homeostatic state is disturbed due to the repetitive apnoeas during sleep.
(Bradley and Floras, 2003) in addition to the disturbance, a negative intrathoracic pressure
will develop in response to occluded airway affecting intrathoracic hemodynamics.
(Shamsuzzaman et al., 2003)

OSA and Cardiovascular Diseases (CVD)

There are many evidences suggesting that OSA can cause cardiovascular diseases such as
hypertension, cardiac arrhythmias, left ventricular dysfunctions, congestive heart failure,
stroke, Coronary Heart Diseases (CHD) and pulmonary hypertension.(Parish and Somers,
2004)

(Somers et al., 2008b)

This figure suggest the relationships between OSA and the pathophysiological mechanisms causing CVD

OSA mechanisms of pathogenesis of CVD

There are many mechanisms that explains relationships between OSA and CVD, and all
mechanisms depend on the fact that normal sleep hemodynamics are altered significantly in
OSA syndrome. (Parish and Somers, 2004)

- Sympathetic activation: abnormalities in cardiovascular regulation develop due to

the increase levels of sympathetic drive(Caples et al., 2005) due to the response to
increased chemoreflex drive resulted from hypoxia and hypercabnia.(Shamsuzzaman
et al., 2003) Cyclic activation of the sympathetic tone affects heart rate, ventilation
and blood pressure due to sympathetic mediated vasoconstrictions.(Garrigue et al.,
2004) (Lopez-Jimenez et al., 2008)

- Endothelial dysfunction and vasoactive substances: Endothelin a vasoconstrictor

substance levels increase in OSA patients, and impair of nitric oxide production
leading to endothelial dysfunction.(Lopez-Jimenez et al., 2008, Somers et al., 2008b)
 - Inflammation: many inflammatory molecules such as C reactive protein and TNF_α
increase in OSA cases and interfering with the endothelium functions. (Lopez-
Jimenez et al., 2008) (Somers et al., 2008a)

- Oxidative stress: a result of cyclic hypoxia – reperfusion injury may also affect the
endothelial and vascular functions due to the production of free radicals.(Lopez-
Jimenez et al., 2008, Somers et al., 2008b)

- Intrathoracic pressure change: increased levels of negative intrathoracic pressure

severely affect cardiac morphology and left ventricular performance. And
increase cardiac after load and venous return, decreasing stroke volume and cardiac
output(Lopez-Jimenez et al., 2008) (Parish and Somers, 2004, Somers et al., 2008b)

- Hypercoagubility: platelets activation is increased due to the role of homeostatic

mechanisms, especially the role of catecholamines involved in regulating blood
pressure.(McNicholas and Bonsigore, 2007)

The prevalence of CVD in OSA

OSA and Hypertension: hypertension is defined as systolic Blood Pressure (BP) of more
than 140 mmHg and diastolic BP of more than 90mmHg.(Lavie et al., 2000)
OSA is considered to be an independent risk factor of the prevalence of hypertension. (Lavie
et al., 2000),(McNicholas and Bonsigore, 2007)
Hypoxia, increased diastolic blood pressure, chemoreceptor stimulation, sympathetic
activation, vascular dysfunction and rennin – angiotensin system have important role in
developing hypertension in response to OSA. (Somers et al., 2008b),(McNicholas and
Bonsigore, 2007)

OSA and Heart Failure (HF): Hypoxia, increased blood pressure and reduced cardiac
contractility are the main causes for HF.(Shamsuzzaman et al., 2003, Bradley and Floras,
2003) Intrathoracic negative pressure during ventilation effort to counter the occluded airway
increases the after load, in addition, the myocardial increased oxygen consumption and
hypoxia controlled by sympathetic activities.(McNicholas and Bonsigore, 2007)

OSA and Stroke: 43 – 91% of stroke patients suffer from OSA,(Leung and Bradley, 2001)
systematic hypertension and increased coagubility are the major causes of stroke.(Leung and
Bradley, 2001) affected by oxygen desaturation during apnoea the chance of developing
plague in OSA patients increases. (McNicholas and Bonsigore, 2007)

OSA and Arrhythmias: mainly caused by the variability of the heart rate during apnoea
reflecting the abnormal pattern of parasympathetic and sympathetic modulations. (Leung and
Bradley, 2001),(McNicholas and Bonsigore, 2007)

OSA and Myocardial Ischemic and Infarction: the mechanisms suggested being the cause
of myocardial ischemic and infarction are due to variable BP and Heart Rate (HR) in apnoeic
patients.(Leung and Bradley, 2001)

References
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