Obstructive Sleep Apnea & Stroke Hold Vengeance Against Each Other

Loud Snoring Disturbs the Snorer & the Person Sleeping Besides Too in Different Ways

There are innumerable satirical comedies and banters surrounding individuals who are loud snorers. Often people sleeping besides the snorer are shown to protect themselves in different ways using props such as pillows or cotton. In worse case, they escape to another room to get some peaceful sleep. We do pity them but do you realize that this is only a short-term or temporary problem and the actual effect finally falls on the snorer. There have even been cases where some marriages have failed as either of the couple was a heavy snorer and the chapter ends there for the party affected badly by the snoring spouse and a new chapter starts for the snorer in terms of devastating health effects if snoring is too much or for too long!

Obesity has been the culprit for a number of health conditions such as heart attack and stroke but it also prevails as the major reason behind some of the risk factors for these conditions as well. Obstructive sleep apnea (OSA) is a sleeping disorder that’s become increasingly prevalent in developing countries that stands as an independent risk factor for stroke and the primary reason behind this exists as obesity. Discovery of diseases and conditions are the results of great efforts by scientists but do you know that a first description of OSA was not from a scientist but from our beloved Charles Dickens in a series of papers titled ‘The posthumous papers of the Pickwick club’ in the form of a character (obese boy) who suffered from excessive daytime sleepiness, loud snoring and right heart failure? But the formal connection between sleep-disordered breathing (SDB) and stroke was first observed in the 19th century and did not achieve prominence about research studies until the 1980s.

SDB is an umbrella term for a constellation of sleep-related breathing disorders and abnormalities of respiration during sleep that do not meet criteria for a disorder and OSA is one of the main disorders included under this umbrella.
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Obstructive Sleep Apnea
OSA is the most common type of SDB which involves repeated narrowing or complete collapse of the upper airway despite ongoing respiratory efforts that’s terminated by arousal from hypoxemia (abnormally low concentration of oxygen in blood) or efforts to breathe. The apnea-hypopnea index (AHI) is calculated by adding together the number of episodes of apnea (absent airflow) and hypopnea (reduced airflow) and then dividing them by number of sleeping hours. AHI values above 5 are defined as OSA with the severity level depending on the AHI value: 5-15 is mild, 15-30 is moderate and AHI greater than 30 is severe.

Suffering from Excessive Daytime Sleepiness is a Sure Sign of Sleep Apnea

OSA is very common in stroke and ischemic stroke patients and also exists as a risk factor for all stroke patients. The awareness on considering sleep apnea and snoring as risk factors for arterial hypertension (HTN), cardiac arrhythmias, coronary artery disease and myocardial infarction came into prevalence only during the late 20th century. Those with untreated sleep apnea are at a higher risk of cardiovascular mobility than those with treated sleep apnea. It is essential to note that one-third of strokes are due to the effects of previous stroke and untreated OSA in patients with stroke could also be a reason for recurrent strokes. Stroke prevalence has a strong connection with the intensity of OSA and with every increase in AHI values the risk of developing stroke goes up. There are 50-70% chances of OSA occurring in patients with stroke. OSA might precede stroke occurrence, worsen during acute stage and linger on after the acute phase. There are various studies since the last couple of decades establishing a bi-directional relationship between SDB and stroke-SBD as a cause and a consequence of stroke. It is better to examine the relationship and understand clearly which dominates the other.

​The Sleep Heart Health Study (SHHS)
There are more than 18 million stroke cases happening annually of which one-third of them are fatal. Besides being the second leading cause of death, it can leave the person with severe disabilities forever which makes it our duty to identify the risk factors and take preventive steps as much as possible to prevent its occurrence. Diabetes, smoking, atrial fibrillation and hypertension are major risk factors and recent research includes OSA too. The SHHS focuses on understanding whether OSA is an independent risk factor for stroke. It is a cohort study that deals with the cardiovascular consequences of OSA.

The study initially included 6,441 participants but some of them were excluded due to various reasons leaving the research team with 2,462 men and 2,960 women. At baseline, all of them were given questionnaires asking about their sleeping habits, general health and medicine use and at intervals of 3 and 5 years after baseline a survey on the diagnosis and treatment for OSA was performed. Blood pressure and blood sugar levels were measured. Obstructive apnea hypopnea index (OAHI) was defined as the average number of obstructive sleep apneas plus hypopneas per hour of sleep. Arousal index is the number of arousals per hour of sleep which had a within-score interclass correlation coefficient of 0.70 to 0.75 and between-scorer interclass correlation coefficient of 0.69 to 0.75.

The study consisted of 5,422 participants all of whom were free from stroke and untreated for OSA followed up for around 8.7 years. In this period 193 of them suffered from ischemic stroke corresponding to an incidence rate of 4.4 ischemic strokes per 1,000 person years.

Results showed that in both men and women ischemic stroke was linked to increasing age and systolic blood pressure, use of antihypertensive medications and atrial fibrillation. In women, the incidence of stroke was linked to race and diabetes but BMI, smoking and alcohol use did not influence both men and women. Men and women who suffered from ischemic stroke during the study had moderate or severe OSA that was 30% more common in them at baseline. The odds ratio (OR) value of 2.26, the increased odds of incident stroke for someone with OSA compared with someone without OSA, is equal to the increased risk associated with a 10-year increase in age. The OR value was much lesser, around 1.65 in the case of women. In both genders, a higher incident rate of stroke was observed with increasing OAHI. Men who had OAHI >19 events/h were at a 3-fold increased risk of ischemic stroke compared to men with an OAHI less than 4.1 events/h. But in women, stroke risk was dependent on age, diabetes, hypertension medication use and smoking but not with OAHI quartiles or desaturation levels. Women with a higher arousal index had decreased chances of stroke incidence-women with an arousal rate greater than 12 had a 40-60% decreased hazard rate of ischemic stroke compared to women with a lower arousal index.

OSA & Stroke
Observational study by Lee et al. heavy snoring increases the risk of carotid atherosclerosis but the Oxford Vascular Study by Mason et al. did not find significant link between repeated snoring episodes and occurrence of carotid atheroma, stenosis or plaque type. There are some studies that show that while sleep apnea indirectly increases the risk of stroke due to its effect on vascular risk factors it is also an independent risk factor for stroke. A study by Yaggi et al. found that AHI≥35/hour in patients with a HR of 2.24 increased the risk of stroke and mortality rates despite controlling for stroke risk factors such as HTN, AF, smoking status, diabetes and hyperlipidaemia. Another study on 394 patients (all of them were males) aged between 70 and 100 years with an AHI≥30 were at a high risk of ischemic stroke. An AHI score ≥20 in 1189 patients increased the risk of stroke in them for the next 4 years. A study by Marin et al. showed that severe OSA increased the risk of fatal and nonfatal cardiovascular events while CPAP (continuous positive airway pressure) treatment reduced the risk. The Wisconsin sleep cohort study showed a higher cardiovascular mortality risk when SDB was left untreated irrespective of age, sex and body mass index (BMI). The SHHS study also proved that men in the highest quartile of AHI had a HR of 2.86 for stroke and did those in the moderate sleep apnea category. Every 1 unit rise in AHI increased stroke risk by 6% in men while in women the risk existed only in those in the severe sleep apnea group.

A 2010 meta-analyses of 29 studies showed that 72% of patients who had a stroke had an AHI >5 and 29% had severe OSA. Prevalence of stroke increases risk of OSA about 5 times more than in the general population. A case-control study by Lipford et al. identified a strong link between OSA and cardiometabolic stroke with paroxysmal AF as a causative factor. Yet another retrospective study on 5,000 patients showed that stroke was more common in patients with the comorbidity of AF and OSA. Poli et al. showed that AF followed by cardioembolism is a major risk factor for stroke on an analysis of 134 patients showing twice the proportion of cardioembolic stroke in SDB patients.

OSA & Stroke Have Certain Common Risk Factors
There are many shared as well as independent risk factors for OSA and stroke. There are studies that show OSA to be a high-risk factor for hypertension which is one of the primary risk factors for stroke and studies do link OSA with other risk factors such as atrial fibrillation (OSA increases risk by 4 times), heart failure, coronary artery disease, insulin resistance and arrhythmia.

When OSA increases stroke risk directly or indirectly those with untreated OSA after stroke suffer from worse functional outcomes and higher mortality rates-it can cause cognitive decline, decreased concentration, excessive daytime sleepiness, prolonged hospitalization and compromised rehabilitation participation.

Obesity is one of the most common risk factors of stroke with increasing BMI linked to increased OSA prevalence. But obesity becomes a less-significant risk factor in those who have had a stroke compared to others. Also, being a male in his advanced years makes you vulnerable to OSA as 65% of post-stroke patients are men.

OSA: How Does it Increase Risk of Stroke?
OSA is ruled by intermittent hypoxemia and arousals resulting in conditions such as hypertension, coronary artery disease, hearty failure, pulmonary hypertension and stroke. Changes in vasodilator and vasoconstrictor substances due to endothelial dysfunction and inflammation happen and these play a role in the atherogenic and prothrombotic states induced by OSA. Blood circulation to brain is altered due to partial pressure of carbon dioxide (Pco2). Sleep apnea causes rise in Pco2 levels causing vasodilation and increased blood flow. Apnea is followed by hyperpnea decreasing Pco2 levels and vasoconstriction. In those with vascular disease increased vasoconstriction can lead to ischemia.

There is indeed a bidirectional association between OSA and stroke as both of them share common risk factors. Besides increasing stroke risk in OSA patients it also elevates functional outcome in these patients. Stroke too has the potential to cause SDB.

References
Obstructive Sleep Apnea-Hypopnea & Incident Stroke: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913239/

Sleep-disordered Breathing and Stroke: Chicken or Egg? http://jtd.amegroups.com/article/view/25986/html

A Sleeping Beast: Obstructive Sleep Apnea & Stroke: https://www.mdedge.com/ccjm/article/201629/sleep-medicine/sleeping-beast-obstructive-sleep-apnea-and-stroke?channel=133

Sleep Apnea and Stroke: https://svn.bmj.com/content/1/4/185

Obstructive Sleep Apnea & Stroke: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340906/
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Early Diagnosis & Treatment of Obstructive Sleep Apnea After Stroke: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3721244/

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