Obstructive sleep apnoea – a marker of increasedcardiovascular risk

Obstructive sleep apnoea (OSA) is the temporary

cessation of breathing due to continuous respiratory

effort against a closed glottis (1). The apnoea causes

repeated episodes of hypoxia and carbon dioxide

retention. The arousal provoked then causes awaken-

ing which restores integrity of pharyngeal dilator

muscle tone and airflow ensues, but as sleep returns

so does the OSA cycle. OSA is measured using the

apnoea–hypopnoea index (AHI) and the definition

includes five or more AHI episodes per hour (mild

5–15, moderate 15–30 and severe over 30). It is not

surprising that daytime sleepiness follows which can

be pronounced and involuntary, and when severe

affects communication (falling asleep at meetings) or

even driving.

Obstructive sleep apnoea is believed to affect 24% of

men and 9% of women which strongly suggests

under-diagnosis. This is important because OSA has

significant cardio and cerebrovascular consequences.

Studies have identified significant and independent

associations between OSA and obesity, hypertension,

coronary artery disease, arrhythmias, cardiac failure,

stroke, the metabolic syndrome, erectile dysfunction

and testosterone deficiency (2,3). The mechanisms

include hypoxia-related autonomic imbalance on

endothelial dysfunction.

During non-rapid eye movement (NREM) sleep,

parasympathetic nervous system tone is increased

and the heart rate, blood pressure, cardiac output

and systemic vascular resistance decreased (4,5). We

could say the cardiovascular system is ‘relaxed’. In

contrast, in rapid eye movement (REM) sleep, sym-

pathetic activity is increased with increases in heart

rate, blood pressure and irregular breathing. Nor-

mally 75–85% of sleep is NREM but OSA shifts the

pattern to increasing REM sleep with adverse cardio-

vascular consequences.

Obstructive sleep apnoea generates negative intra-

thoracic pressure, increasing right heart venous

return and distension of the right ventricle, whilst

increased sympathetic activity causes vasoconstriction

and an increase in afterload (6). The right ventricular

septum impinges on the left ventricle (LV) in dias-

tole, reducing LV filling and stroke volume as well as

delaying LV relaxation (7). Left atrial volume is

increased and atrial fibrillation may develop which in

the OSA-induced hypercoaguable state combines

cerebral hypoxia with the risk of emboli (8). The

presence of a patent foramen ovale which is seen in

10–25% of individuals undergoing transoesophageal

echocardiography will then be a further risk for

stroke (9).

Obstructive sleep apnoea certainly increases and is

a marker of increased risk for stroke (10). In addi-

tion, in randomised clinical trials, OSA causes hyper-

tension and importantly its treatment lowers blood

pressure [continuous positive airways pressure

(CPAP)] (2). CPAP also improves systolic function,

decreasing the adverse effects of the sympathetic ner-

vous system, and improves myocardial oxygen supply

(less nocturnal ischaemia) and a reduction in cardio-

vascular events (2,11). The OSA-related adverse

increase in aldosterone raises the question of angio-

tensin receptor antagonists as a means of therapy.

Reducing obesity is the obvious preventative measure

and an ear, nose and throat specialist opinion should

rule out a mechanical cause (12).

Obstructive sleep apnoea is often associated with a

history of regular snoring due to increased pharyn-

geal airways resistance. Snoring is often a joked

about family issue, but it could well be a reflection

of OSA and an explanation for ‘he died in his sleep’.

Disclosures

None.

Graham JacksonEditor

Email: gjcardiol@talk21.com

References1 Young T, Palta M, Dempsey J, Skatrud J, Weber S,

Badr S. The occurrence of sleep-disordered breath-

ing among middle-aged adults. N Engl J Med 1993;

328: 1230–5.

2 Bradley TD, Floras JS. Obstructive sleep apnoea

and its cardiovascular consequences. Lancet 2009;

373: 82–93.

3 Gami AS, Somers VK. Obstructive sleep apnoea,

metabolic syndrome, and cardiovascular outcomes.

Eur Heart J 2004; 25: 709–11.

4 Mancia G. Autonomic modulation of the cardiovas-

cular system during sleep. N Engl J Med 1993; 328:

347–9.

5 Phillipson EA. Control of breathing during sleep.

Am Rev Respir Dis 1978; 118: 909–39.

6 Leung RS, Bradley TD. Sleep apnea and cardiovascu-

lar disease. Am J Respir Crit Care Med 2001; 164:

2147–65.

7 Virolainen J, Ventila M, Turto H, Kupari M. Influ-

ence of negative intrathoracic pressure on right

atrial and systemic venous dynamics. Eur Heart J

1995; 16: 1293–9.

EDITORIAL

ª 2012 Blackwell Publishing LtdInt J Clin Pract, May 2012, 66, 5, 421–424 421

OSA has

significant

cardio and

cerebro-

vascular

consequences

8 Leung RS, Huber MA, Rogge T, Maimon N, Chiu

KL, Bradley TD. Association between atrial fibrilla-

tion and central sleep apnea. Sleep 2005; 28: 1543–

6.

9 Serena J, Jimenez-Nieto M, Silva Y, Castellanos M.

Patent foramen ovale in cerebral infarction. Curr

Cardiol Rev 2010; 6: 162–74.

10 Ryan C. OSA – a risk factor for stroke. Chronophys-

iol Ther 2011; 1: 43–57.

11 Shamsuzzaman AS, Gersh BJ, Somers VK. Obstruc-

tive sleep apnea: implications for cardiac and vascu-

lar disease. JAMA 2003; 290: 1906–14.

12 Smith PL, Gold AR, Meyers DA, Haponik EF,

Bleecker ER. Weight loss in mildly to moderately

obese patients with obstructive sleep apnea. Ann

Intern Med 1985; 103: 850–5.

doi: 10.1111/j.1742-1241.2012.02931.x

ED ITORIAL

Do the current atrial fibrillation guidelines for strokeprevention need to be changed with the availabilityof new data on the new oral anticoagulants?

In 2010, we saw an updated version of the European

Society of Cardiology (ESC) guidelines for the man-

agement of atrial fibrillation (AF) (1). One signifi-

cant change from the previous version of the

guidelines from 2006 was the section on stroke risk

prevention. A notable move was the de-emphasis of

the ‘low’, ‘moderate’ and ‘high’ risk strata for stroke,

given the poor predictive value of such artificial risk

categories, and emphasising that risk of stroke in AF

was a continuum and evolved over time. Indeed,

prior guidelines focused on identifying the ‘high risk’

patients, who could be targeted for anticoagulation

with an ‘inconvenient’ (and potentially dangerous)

drug, warfarin.

With the imminent availability of new oral antico-

agulants with significant efficacy, safety and tolerabil-

ity advantages over warfarin, the focus has shifted, so

that we were better at identifying ‘truly low risk’

patients who did not need any antithrombotic ther-

apy, whilst those with one or more stroke risk factors

could be considered for oral anticoagulation, whether

with well-controlled warfarin or with one of the new

agents (2).

Hence, the new ESC guidelines recommended the

use of the CHA2DS2VASc score to complement the

older, simple CHADS2 score (1) (see Table 1).

Given that guidelines should be applicable for

> 80% of the time, for > 80% of the patients, the

ESC guideline stroke risk assessment approach cov-

ers the most of the patients we commonly seen in

everyday clinical practice, and considers the com-

mon stroke risk factors in such patients. The ESC

guidelines also stress that antithrombotic therapy is

necessary in all patients with AF unless they are age

< 65 and truly low risk. Thus, some patients with

‘female gender’ only as a single risk factor (still a

CHA2DS2-VASc score = 1) would not need antico-

agulation, if they fulfil the criteria of ‘age < 65 and

lone AF’.

Do the 2010 ESC guidelines need updating, given

the publication of exciting phase III trials of the new

oral anticoagulants for stroke prevention in AF? The

new oral anticoagulants are broadly classified into

two classes: the oral direct thrombin inhibitor (DTI)

and oral factor Xa inhibitors with impressive efficacy

and safety results in their trials (3–5). The novel an-

ticoagulants simplify anticoagulation by having fixed

doses, predictable pharmacokinetics requiring no

blood monitoring and less drug or food interactions,

compared with warfarin.

The first major trial was the RE-LY trial (3), which

was an open label trial comparing dabigatran 150

and 110 mg BD to dose adjusted warfarin (INR 2-3),

demonstrated superior efficacy of the 150 mg BD

dose for the endpoint of stroke or systemic embo-

lism, similar rates of major bleeding and significantly

reduced intracranial haemorrhage (ICH). Indeed, this

was a landmark trial, which showed that a new oral

anticoagulant (in this case, dabigatran 150 mg BID)

could show superior efficacy for stroke prevention

(with a significant reduction in both ischaemic stroke

and haemorrhagic stroke) with similar rates of major

bleeding to warfarin, as well as significantly less

intracranial haemorrhage (ICH) or the composite of

‘major plus minor’ bleeding. Vascular mortality was

significantly reduced, with a borderline reduction in

all cause mortality.

The next major published trial against warfarin

was with the oral factor Xa inhibitor, rivaroxaban.

Despite a half life shorter than both dabigatran and

apixaban at 6–9 h, rivaroxaban was tested as a once

daily 20 mg dose (with a dose adjustment to 15 mg

422 Editorials

ª 2012 Blackwell Publishing LtdInt J Clin Pract, May 2012, 66, 5, 421–424

Do the

current atrial

fibrillation

guidelines

for stroke

prevention

need to be

changed?