Carrie Fisher and sleep apnea

I've seen a few articles now on the suspected cause(s) of Carrie Fisher's death (the actress who played Princess Leia). I was hesitant to blog about it, but thought I should as the articles are mentioning sleep apnea. Apparently, the autopsy report did list sleep apnea as a potential contributor. The article I am referencing does a good job explaining what sleep apnea is, the different types, the consequences of untreated sleep apnea and how certain drugs / medications can worsen sleep apnea. I agree with the bottom line that the chance of dying from sleep apnea is low, but gets higher with untreated sleep apnea and drug use.

Sleep apnea and insomnia on the rise in the US Military

This article shows how both sleep apnea and insomnia diagnoses have increased from 2005 - 2014. In my clinic, both conditions make up the bulk of the diagnoses and often exist together. The article states how the rates are higher in more senior personnel. This may be because sleep apnea is more prevalent with advancing age. Also, I frequently see senior personnel who are close to retiring, and have decided to start taking care of themselves. Usually it's because they finally have time to get their medical problems addressed as they approach separating from the military. Some of them wish they had gotten evaluated years prior, as treating their sleep apnea can significantly improve their quality of life.

CPAP may improve PTSD in Veterans with sleep apnea

This article discusses research about post-traumatic stress disorder (PTSD) and obstructive sleep apnea (OSA). There have been research studies linking PTSD and OSA, possibly because of OSA-related sleep disruption. In particular, OSA can be more frequent in dream sleep, resulting in more dream sleep fragmentation. This could cause more nightmares, or at possibly more awareness of nightmares. In this study, the authors sought to determine if CPAP therapy for OSA also reduced PTSD severity in US Veterans.

The results showed a modest reduction in PTSD symptoms in patients with OSA treated with CPAP for 6 months. And the more nights someone used their CPAP, the less severe the PTSD symptoms. There were also improvements in sleep quality, daytime functioning, and quality of life.

Natural history of excessive daytime sleepiness

This article examines the natural history of excessive daytime sleepiness (EDS). In the article, the authors explain that EDS affects about 30% of the general public. They also explain that EDS is associated with certain psychiatric, metabolic, and sleep disorders. I would add that EDS is also a result of insufficient amount of sleep and sedating medications.

In this study, participants had a comprehensive sleep history and physical exam along with an in-lab overnight sleep study at baseline. No daytime sleepiness study, called the Multiple Sleep Latency Test (MSLT), was performed - sleepiness was only determined subjectively. Sleep apnea was defined at a cutoff that is standard for moderate severity - it's not explained why they did not include those with mild sleep apnea, who could be just as sleepy as more severe levels. Finally, follow up was only through telephone interview - no repeat sleep study or physical examination was done. The follow up was 7.5 years after the baseline evaluation, on average. Therefore, there are some important limitations to this study.

Incident EDS was defined as those who had no EDS at baseline but did have it at follow up. Remitted EDS meant those that had EDS at baseline, but not at follow up. And persistent EDS meant those that had EDS at both baseline and follow up. Results showed that incident EDS was 8.2%, and was more commonly associated with male gender, non-Caucasian race, and younger and older age. Depression, sleep apnea, obesity, and diabetes were also associated with incident EDS. Sleep duration less than 5 hours or more than 8 hours was associated with incident EDS. However, insomnia was not associated with incident EDS. Snoring was related to incident EDS, especially in those with sleep apnea.

The persistent EDS rate was 38%, whereas 62% had remitted EDS. Persistent EDS was associated strongest with anemia and insomnia. Individuals with incident or persistent EDS gained significantly more weight when compared to those without EDS. Also, individuals with remitted EDS gained significantly less weight compared to those without EDS.

The authors concluded that obesity, depression, and sleep disorders should be a public health priority to improve EDS.

Treating obstructive sleep apnea with medication

Obstructive sleep apnea (OSA) is currently treated with mechanical devices - air pressure from CPAP, jaw movement with oral appliance therapy, or surgical therapy. No medications have been shown to be particularly helpful in treating OSA. This article discusses NIH funding given to a team of researchers at the University of Chicago.

The article describes the research already going on at the University that focuses on a small group of cells in the carotid artery called the carotid bodies. When levels of oxygen in the blood drop, these carotid bodies send signals to the brainstem to increase breathing, with the goal of increasing oxygen levels in the blood. The article describes that in sleep apnea, the carotid bodies may not react appropriately, and thus stop sending signals to the brain. The University of Chicago team has developed a compound that may help the carotid bodies to keep working properly during sleep apnea, and thus aid in their regulation of breathing - at least in rodents.

However, it's not clear what type of sleep apnea the researchers are working on. It sounds like central sleep apnea (CSA), which is a completely different, and less common form of sleep apnea, than OSA. In most cases of OSA, the drive to breathe is intact, but airflow is significantly reduced due to a blockage in the upper airway. In addition, not every patient with OSA has oxygen level reductions, even though airflow through the upper airway is reduced. But if a person with OSA has regular blood oxygen level reductions, perhaps a medication that helps the carotid bodies stimulate breathing may be effective, if that stimulation involves increasing the diameter of the upper airway.

Rising prevalence of obstructive sleep apnea

Obstructive sleep apnea (OSA) is becoming more common in the U.S. When I was a sleep disorders fellow, it was thought that OSA occurred in 2% of women and 4% of men. This article highlights how the rates of OSA have increased in the past two decades. Apparently, OSA now is present in at least 25 million adults in the U.S. and in 26% of adults between the ages of 30 and 70 years old.

The article discusses the complications of untreated OSA too. It does not discuss why the prevalence rates have risen. I suspect more public awareness of the symptoms, more acceptable treatment options, rising obesity rates, and aging population contribute to the increase in OSA rates.

Sleeping pills and heart failure

Patients with heart failure are at increased risk of having sleep difficulties. Sleep-related breathing difficulties like sleep apnea are also more common in heart failure patients. Here is a study that looked at sleeping pills and heart failure patients. Specifically, the researchers investigated the relationships between drugs prescribed at hospital discharge, going back into the hospital, and cardiovascular events in heart failure patients.

The results showed that sleeping pills increase the risk of cardiovascular events in heart failure patients by 8-fold. The type of sleeping pills that were most risky were the benzodiazepines like valium. At the end of the article, the researchers speculate that benzodiazepine sleep aids could reduce cardiac function or cause respiratory depression, and this could worsen any underlying sleep-related breathing disorders. The latter is certainly possible and underscores the importance of heart failure patients getting evaluated for sleep apnea. Prior to prescribing sleep aids, it's best to rule out sleep-related breathing disorders. If sleep apnea is present, that needs to be treated, rather than just giving sleep aids.

9/11 and sleep apnea

Here is an article about how workers who were first responders to 9/11 have elevated risk of sleep apnea and post-traumatic stress disorder (PTSD). The article does not go into detail about the mechanism of action. I wonder if the rate of sleep apnea is higher due to localized inflammation in the upper airway due to the particulate matter inhaled at the scene. I could also envision higher rates of pulmonary disease from inhalation of particulates, but that was not mentioned in the article.

Sleep apnea impairs driving ability

Obstructive sleep apnea (OSA) can increase sleepiness, which can impair your ability to safely drive. Here is an article about two studies showing just that. Both studies involve longer distances on a driving simulator. So keep that in mind, as driving for real may be different. People with untreated OSA were more likely to fail the simulator test than those without OSA. Also, those with untreated OSA were more likely to admit to nodding off behind the wheel than those without OSA. Neither study tested the drivers after they received OSA treatment - those studies will be interesting to see.

Whether you have OSA or not, always use precaution when driving. Do not drive if you feel sleepy. If you get sleepy while driving, pull over to a safe area and take a brief nap. Or if you are with someone else, let them drive so you can nap in the car.

CPAP can boost worker productivity

Obstructive sleep apnea (OSA) can reduce worker productivity if untreated. This study showed that workers that regularly used a CPAP when they slept were more productive. And productivity did not improve in those with OSA that did not use their CPAP.

Sleep apnea may impair kids behavior and adaptive functioning

Studies have shown that kids with obstructive sleep apnea (OSA) can have behavioral difficulties that affect school and home. Some will present to their pediatrician with symptoms of attention deficit-hyperactivity disorder (ADHD) - but in reality, the cause is underlying OSA. This study in the Journal Sleep looked at how kids with OSA have increased risk of behavior and adaptive functioning difficulties. Adaptive functioning refers to how these kids "negotiate social situations, engage in self-care to meet his or her own needs, and apply skills learned in school."

Researchers studied 263 kids starting at ages 6-11 years old. They had the kids and parents fill out questionnaires about behavior and functioning. They had the kids do home sleep studies. Then 5 years later, they repeated the questionnaires and sleep studies.

The results showed that the highest rate of impairment occurred in those kids diagnosed with OSA, particularly those that had it on both sleep studies (5 years apart). Researchers note, however, that some behaviors, like aggression and conduct problems, were accounted for by sociodemographic variables, rather than the OSA. And kids who had OSA on both sleep studies were 3-7 times more likely to have learning problems and lower grades than in kids who never had OSA.

CPAP may reduce inflammation associated with sleep apnea

Obstructive sleep apnea (OSA) causes inflammation - both local and systemic. Researchers think that the local inflammation is from trauma from snoring. Systemic inflammation may occur because of repetitive drops in blood oxygen levels and / or sleep fragmentation from OSA. This study did a meta-analysis to see if CPAP reduces three markers of systemic inflammation - CRP, IL-6, and TNF-alpha. The data showed that CPAP use did significantly reduce levels of CRP and TNF-alpha. It lowered levels of IL-6, but not enough to be statistically significant.

The bottom line is that untreated OSA is associated with systemic inflammation, which may raise the risk for cardiovascular disease. Treating OSA with CPAP can reduce some of the markers of inflammation - this may lower the risk of developing cardiovascular disease.

Sleep apnea may increase risk of brain tumor

Obstructive sleep apnea (OSA) can cause repetitive dips in blood oxygen levels, which can then cause chronic inflammation. Some researchers think this chronic inflammation may increase risk of cardiovascular disease, lowered immunity, and increased risk of tumors. This study showed an increase risk of brain tumors in patients with sleep apnea. The article does not describe the OSA severity - is it only in severe OSA sufferers? Or is there risk increased even with mild OSA? Does it depend on how the researchers defined apnea events - with oxygen level dip and/or arousal in brain wave monitoring? More questions than answers at this point.

Sleep Apnea Increases Pulmonary Complications After Surgery

There is an article in the January issue of Anesthesia & Analgesia that warns that patients with sleep apnea have more frequent pulmonary complications after orthopedic and general surgery. I am not sure if this included sleep apnea patients that were treated. The risk of being intubated and put on a mechanical ventilator went up five-fold after orthopedic surgery and two-fold after general surgery. Other complications that were increased after these surgeries included aspiration pneumonia (lung infection after stomach contents are inhaled) and pulmonary embolus (lung clots).

This study points to the importance of pre-surgical screening for sleep apnea, so that anesthesiologists and surgeons are aware of the risk. Also, it would be interesting to know if treating sleep apnea reduces these pulmonary risks.

Sleep Symptoms and Metabolic Syndrome

An article in the December issue of the Sleep Journal has received media attention, so I thought I would summarize it here.

Metabolic syndrome is defined as having three or more of the following: elevated blood glucose, increased waist circumference, high blood pressure, increased triglycerides, and low HDL (the good cholesterol). It is estimated that 20% of us have the metabolic syndrome.

The authors of this study assessed over 800 people ages 45 to 74 over a three year period to see if they developed the metabolic syndrome and if it was associated with any sleep symptoms. They used a subjective questionnaire to assess insomnia symptoms, loud snoring, gasping at night, and/or nighttime choking. Sleep duration was not assessed. Almost 300 of the study participants volunteered to have a home sleep study (Resmed's ApneaLink) at the end of the three years.

Over the three year span of time, 14% developed the metabolic syndrome. The sleep symptoms that were statistically related to metabolic syndrome were difficulty falling asleep, unrefreshing sleep, loud snoring, and elevated score on the ApneaLink home sleep study. There was no interaction with race of gender. Loud snoring was most predictive, more than doubling the risk of developing metabolic syndrome. As expected, insomnia syndrome did not raise the risk of metabolic syndrome.

The study authors were not able to tell if the patients who claimed loud snoring also had the elevated sleep apnea severity as measured by the ApneaLink. This would have been helpful because the authors concluded that loud snoring by itself is a risk factor in developing metabolic syndrome. I'm not convinced that loud snoring without sleep apnea is physically dangerous to patients.

It was interesting that difficulty staying asleep did not significantly raise the metabolic syndrome risk, but difficulty falling asleep did. This goes against my clinical experience of how many sleep apnea patients sleep - most fall asleep easily, but just can not stay asleep. The authors suggested that the difficulty falling asleep could be due to emotional and/or physiologic hyperarousal, which could be due to increase nervous system activity and elevated cortisol levels. These have been linked to insulin resistance and the metabolic syndrome.

For me, the conclusion from this study is that you should seek a sleep evaluation from your doctor if you have loud snoring and/or difficulty falling asleep.

Snoring and Obstructive Sleep Apnea

In the October (yes, I am behind) edition of the Journal of Clinical Sleep Medicine, there is an article about how snoring correlates with the severity of obstructive sleep apnea (OSA). Snoring occurs in 25% of women and 45% of men, and is the most common symptom of OSA. Snoring is considered a "cosmetic" issue and is not associated with other illnesses like high blood pressure, cardiovascular disease, stroke, or metabolic syndrome, the way OSA is.

This study was the first one to use an objective measurement of snoring intensity in a large (>1600) group of patients to determine the relationship between OSA and snoring loudness. They measued snoring during a sleep study with a digital sound meter. In this study, there were more males than females. Men were older, heavier, and had larger neck circumferences than women.

The results showed that men had louder snoring than women (big surprise, huh?), and this was consistent across all sleep stages, body positions, and weight. Snoring was louder among those that were heavier, had larger neck sizes, and when sleeping on the back, regardless of gender. Snoring was more common in non-dream (NREM) than dream (REM) sleep. As expected, snoring got louder as the OSA got more severe. I've told patients about this observation in my clinical practice, and now there is objective proof.

Sleep Duration and Stroke Risk

A study was presented at the American Heart Association meeting where almost 70,000 female nurses were asked how long they slept on average over a 20 year span of time. The researchers than recorded which women had a stroke and analyzed if a certain number of hours of sleep increased the risk of stroke relative to the baseline average of seven hours per night.

The researchers found that women who slept 10 or more hours had a 63% increase risk of stroke. Those women that slept less than 7 or 8-9 hours per night had an insignificant increase in stroke risk. Of note, the researchers adjusted the risk for other factors like alcohol intake, fruit and vegetable consumption, physical activity, and smoking status. Body mass index and the presence of diabetes and high blood pressure were recorded as potential influential factors.

The researchers were unable to determine any underlying biological mechanism that could cause the increased risk of stroke in longer sleepers.

I wonder if some of the women have untreated sleep apnea, which can cause longer sleep durations, in an attempt to get more rest. Untreated sleep apnea does increase the risk of stroke.

Longer sleep durations could mean that these women have brains that function differently or are structurally different, and perhaps those differences could account for the increased stroke risk.

Obstructive Sleep Apnea and Coronary Artery Disease

In 2005, a study was undertaken to to address the impact of continuous positive airway pressure (CPAP) on patients who had undergone revascularization for coronary artery disease (CAD) and who had documented obstructive sleep apnea (OSA). The study is still ongoing, and researchers have found that the prevalence of OSA is 64% in the CAD population. Hypertension, or high blood pressure, is 58% and obesity is 28% prevalent in CAD.

Patients with CAD and OSA were older, more obese, more often male gender, and had higher incidence of hypertension, diabetes, and atrial fibrillation than those patients with CAD but not OSA.

Interestingly, the risk of CAD was the same in patients with OSA, regardless of their level of sleepiness. And the only difference in the comorbidities of sleepy versus non-sleepy OSA patients was obesity, which was more common in the sleepy OSA patients.

The researchers also studied CPAP compliance. At one year of follow-up, 70% of sleepy OSA patients with CAD were still using their CPAP compared to 60% of non-sleepy OSA patients. This makes sense, as more symptomatic OSA patients are more likely to keep using their CPAP.

The study will conclude in 2012 and the researchers are hoping to prove that treatment of OSA with CPAP will offer patients a non-pharmacologic intervention to reduce the risk of cardiovascular disease.

Older Women and Sleep Apnea Symptoms

There is a summary from Reuters of an article in the September 3rd online paper in the European Respiratory Journal Express. The study authors examined 379 women and 262 men with obstructive sleep apnea (OSA) ages 65 to 70 years old. Specifically, it looked at the different symptoms of OSA in older men versus women.

In this study, more men had severe OSA than women. Men also had a greater body mass index. The women were less likely to report snoring, apnea, or sleepiness, and more likely to be anxious and depressed, and be taking antidepressants and anti-anxiety medications.

This goes along with my clinical experience. Women (not just older women) report less snoring and apneas than men. It could be because they don't snore as much or as loud. Also, their husbands are sometimes less in tune to their wives sleep problems. Since patients rely on bed partners to note snoring or apneas, some women might never realize they are doing that in their sleep. All they know is that they might not sleep well or feel tired or sleepy in the daytime.

Finally, the study authors said older women with OSA were a greater hypertensive (high blood pressure) risk than men, and therefore may have greater cardiovascular mortality and morbidity. This would emphasize the need for early diagnosis to prevent cardiovascular risk. This is true to a point. When a patient reaches a certain age, treating OSA just to prevent cardiovascular disease becomes a "numbers" game. In other words, treating asymptomatic OSA in an 85 year old (male or female) is less likely to prolong life than in a 55 year old, since the 85 year old has already lived longer than the average US lifespan. However, often I suggest treatment in the older patients to improve quality of life, even in those who do not endorse overwhelming symptoms.

Insomnia, Sleep Duration, and Mortality

In the September edition of the Sleep Journal, there is an article about the association of insomnia, sleep duration, and insomnia. The authors followed adult men and women to assess death rates. The study participants were assessed with a comprehensive sleep history and physical exam and one night in the sleep laboratory. Insomnia was defined subjectively as an insomnia complaint that lasted for one year. Sleep duration was defined as short if it lasted less than 6 hours per patient's report.

The results showed that in men, the mortality rate was increased for insomniacs with short sleep duration and this was independent of age, race, obesity, alcohol consumption, smoking, obstructive sleep apnea, or depression. The effect was not mitigated by the presence of high blood pressure or diabetes.

There was no increased mortality in women, whether or not they were short sleepers or had insomnia. Also, the association with sleep duration was only for the subjective report, and not based on the duration of sleep measured objectively in the sleep lab.

This study purports to be the first one to link insomnia with mortality. However, the average follow up was 14 years in the men, meaning their sleep study was done at a time when only airflow was routinely monitored. This means that nasal pressure transducers were not used, and therefore sleep apnea could have been present in these men. Sleep apnea is more prevalent in men which could explain why the mortality rate was increased for men and not women.

I'll concede that some patients with insomnia can have a revved up nervous system, referred to as hyperarousal. This, theoretically, could increase cardiovascular disease. But the results of this study do not prove that insomnia by itself increases mortality. Objective monitoring of sleep duration at home over extended periods of time will help answer this question more completely.