High blood pressure medications and obstructive sleep apnea severity

Obstructive sleep apnea (OSA) is associated with high blood pressure (HTN). Studies have shown that OSA is independently associated with resistant HTN and it is believed that untreated OSA may worsen HTN. However, studies involving treatment of OSA with continuous positive airway pressure (CPAP) have demonstrated only modest improvement in daytime blood pressure in randomized control trials. some research first speculate that the relationship between OSA and HTN may be bidirectional.

With OSA, the muscles that make up the throat lose their home causing collapse of that area and reduction in airflow to the lungs. Research her as hypothesized that intensive blood pressure control may influence always say I stabilizing the upper airway. There is also evidence for the role of volume status affecting the severity of OSA. What this means is that some people have worse OSA when they have too much blood volume from conditions like heart failure or kidney failure.

This study theorized that it is at least plausible that intensive treatment of HTN may bring about improvement in the severity of OSA, either by volume control, stabilization of upper airway muscles, or perhaps because of some direct effect of blood pressure medications. The researchers conducted a systematic review and meta-analysis on this topic.

Although there were limited number of studies and the studies were not of high quality, though results revealed that there was a decrease in OSA severity after treatment with blood pressure medications. Of note, the decrease reached statistical significance but the researchers doubted if it would be clinically significant.

I wanted to blog about this study in part because because throughout my career as a sleep physician I have thought of the OSA-HTN relationship as more one way, with OSA contributing to HTN, rather than the opposite as suggested by the authors of this study. Certainly more studies will be required before any definitive conclusions can be made.

High blood pressure and insomnia

Insomnia refers to an inability to sleep the desired amount despite adequate allotted time in bed. People with insomnia often misperceive their sleep duration. Research studies have linked chronic insomnia with increased risk of high blood pressure (HTN). Sleeping less than 6 hours is considered being a "short sleeper" and is also associated with HTN.

This study looked at the association between short sleepers with insomnia and HTN. Participants underwent two consecutive in-lab sleep studies to objectively monitor sleep duration. They also had the participants record their subjective sleep duration with a sleep diary. Results showed that insomnia with objectively-measured sleep duration less than 6 hours was associated with increased risk (Odds Ratio 3.59) for HTN. This finding was independent of the following confounders: age, gender, race, body-mass index, frequency of sleep aid use, sleep apnea severity, daytime sleepiness, diabetes, high cholesterol, depression, alcohol use, tobacco use, or caffeine consumption.

The authors concluded that the results provide further support for measuring sleep duration objectively, rather than subjectively for those patients with chronic insomnia. This means the authors are advocating for sleep studies in the evaluation of chronic insomnia to help determine morbidity risks associated with the insomnia.

Sleep apnea and high blood pressure

Another post about obstructive sleep apnea (OSA) and high blood pressure (HTN). This study is a meta-analysis of observational studies and randomized controlled clinical trials. The study authors studied patients with resistant HTN, meaning blood pressure that was not responding to multiple medications. The study participants also had OSA.

I don't have access to full article, only the link above and the abstract. The results suggest that those patients with the highest blood pressures had the greatest reduction in blood pressure after using CPAP therapy. The study authors concluded that untreated OSA may be why some patients' blood pressure just won't come down with multiple medications.

The results from this study are not new, but do provide more evidence of the importance of screening patients with resistant HTN for underlying OSA. In my community, primary care doctors have been doing this for years already. However, this may not be the case in other medical communities around the country.

Blood pressure and sleep apnea

Several research studies have linked high blood pressure (HTN) to obstructive sleep apnea (OSA). The etiology is not clear, however. With OSA, there is sleep disturbance from brief awakenings, thought secondary to adrenaline release that is triggered when breathing resumes. Also, oxygen level reductions, called desaturations, could lead to elevated blood pressures. Respiratory events that are detected during a sleep study have specific scoring criteria - the event has to last at least 10 seconds and result in either a brief arousal from sleep and / or an oxygen desaturation.

This study sought to determine which types of respiratory events were most likely to result in HTN. The researchers followed 2040 participants and used sophisticated statistical models to study the sleep study results and blood pressure measurements. Results showed that those respiratory events with at least a 4% oxygen desaturation were most consistently associated with HTN. Interestingly, the other sleep study measurement that correlated with HTN was periodic limb movements that resulted in brief arousals from sleep.

Sleep-disordered breathing in pregnancy

I've blogged before here, here, and here about pregnancy and breathing disorders in sleep. We know that the prevalence of sleep-disordered breathing (SDB) symptoms increases the further along in the pregnancy. This could be due weight gain and swelling that occurs as pregnancy progresses.

Some studies have shown an association between SDB and pregnancy-related illnesses like high blood pressure, gestational diabetes, and pre-term birth. However, many of these studies relied on subjective assessment of SDB. This study was done to look at the relationship of objectively assessed SDB and certain pregnancy-related illnesses. A home sleep study was performed on pregnant women twice - once between 6 - 20 weeks and again between 28 - 37 weeks. Results showed that 30% of the pregnant women had SDB early pregnancy. However, there was no relationship between SDB and maternal high blood pressure (called preeclampsia), preterm birth, or extremes of birthweight (low or high). There was a relationship between SDB severity and risk of developing gestational diabetes, even after controlling for confounding factors like age, race, body-mass index, hx of chronic high blood pressure, etc.

Despite the observed relationship between sleep-disordered breathing and gestational diabetes, the study authors pointed out that there is no evidence that treatment of the SDB in the short term improves maternal or neonatal outcomes.

Insomnia and high blood pressure

Primary insomnia means difficulty sleeping not due to another medical or sleep disorder. It's a common problem but has not been conclusively linked with increased risk of medical illness. It has been shown to increase risk of depression. Part of what I do when I treat chronic insomnia is to explain that insomnia by itself is not medically dangerous. The studies that have shown links between insomnia and medical problems have not distinguished primary from secondary insomnia. Insomnia secondary to obstructive sleep apnea (OSA) can increase risk for cardiovascular (CV) disease, but it's the OSA, not the insomnia that is raising the CV risk.

Here is an article confirming what's already known about primary insomnia and high blood pressure. The results showed no link between insomnia and high blood pressure, even for 'severe' insomnia.

Sleep apnea and cardiovascular effects

Obstructive sleep apnea (OSA) is associated with high blood pressure and cardiac arrhythmias. When someone has a sleep apnea event, their heart rate typically slows down. Heart rate then speeds up during the subsequent recovery breaths. It's this repetitive slow-fast cycle during the night that is thought to contribute to arrhythmia. And research has shown that the more oxygen levels decrease during sleep apnea, the greater the risk to the heart and blood vessels. This study was done in a rat model of OSA. The results showed that the low oxygen levels from OSA damaged vital neurons in the rats' brains that regulate blood pressure and heart rate. This could explain why OSA increases risk of high blood pressure and cardiac rhythm problems. More research will be needed to determine if treating OSA can reverse the damage to those neurons.

Sleep loss and metabolic syndrome

Metabolic syndrome is a chronic disorder characterized by abdominal obesity, impaired blood sugar metabolism, high cholesterol, and high blood pressure. Here is an article about sleep loss and it's affect on our metabolism. The article is a review of the observational studies that examine the relationship between sleep deprivation and metabolic syndrome. The authors discuss some of the studies that show that acute sleep loss is linked with obesity, type 2 diabetes, cholesterol problems, high blood pressure, and even death. Of note, some of the studies show increased rates of some of these issues when people report sleeping less than or more than a specified "normal" amount of sleep. So it's not just sleep loss that is linked to problems, including mortality.

The authors note that sleep loss can affect appetite, food intake, physical activity levels, and energy expenditure. Again, these are short term studies and the reasons for the changes are not entirely clear. Results sometimes are conflicting, such as some studies showing higher levels, and other studies showing lower levels of appetite regulating hormones.

The authors conclude that sleep loss may be a "promising target for the prevention, and probably the treatment, of the metabolic syndrome and its components." Perhaps that is the case, but telling people to get more sleep is unlikely to improve their metabolic syndrome. It's certainly more complicated than that. Diet and exercise are just as important, and most likely much more so than just getting more sleep. I concede that insufficient sleep may contribute a small part to metabolic syndrome, but more long term studies are needed. And I agree with the authors when they conclude that ongoing and future studies will show whether interventions to improve sleep duration and quality can prevent or even reverse adverse metabolic traits."

CPAP therapy may improve blood pressure in resistant high blood pressure

Obstructive sleep apnea (OSA) has been linked to high blood pressure (HTN). In fact, one cause of reversible HTN is untreated OSA. And sometimes we see improvement in HTN with treatment of OSA, especially severe OSA. Here is a study that showed just that. Researchers studied patients with resistant HTN and moderate-to-severe OSA. The results showed that blood pressure dropped significantly after 6 months of CPAP therapy, compared to those patients who did not receive CPAP therapy.

Diabetics and those with high blood pressure should be tested for obstructive sleep apnea

Here is an article from the annual sleep meeting last week. The American Academy of Sleep Medicine recommends evaluation for patients with high blood pressure and type 2 diabetes, since they are at increased risk of having obstructive sleep apnea.

Periodic limb movements in sleep, heart abnormalities, and hemodialysis

Periodic limb movements in sleep (PLMS) are repetitive, small leg jerks that occur during sleep, usually without any memory of it happening. However, PLMS can fragment sleep and have been linked to increased cardiovascular risk factors. Restless legs syndrome (RLS) is linked to PLMS - most RLS patients have PLMS. RLS and PLMS are common in hemodialysis patients. And hemodialysis itself is linked to cardiovascular disease. This study sought to determine if patients with RLS and PLMS on hemodialysis had a deterioration in heart structure and function compared to those RLS patients without PLMS.

Researchers used a cutoff value for the PLMS that puts them in the moderate to severe amount - this is most likely to be clinically significant. Results showed that resting heart rate and blood pressure (BP) were similar in those with and without PLMS. The minimum systolic BP (referring to the 120 in "120 over 80" for example) was higher in the PLMS group. Also, the percent reduction of BP during sleep, compared to being awake, was 50% smaller in the PLMS group. This means that those with PLMS did not experience as much a dip in BP during sleep - something that could lead to high blood pressure in the daytime. The mass of the left side of the heart was greater in PLMS group, but both groups had hearts that could pump out the same amount of blood per beat.

The authors concluded that PLMS can alter the structure of the heart, but not necessarily its function. They feel that PLMS do this by raising blood pressure during sleep. The heart gets larger when it has to pump against a higher blood pressure, which can lead to the results obtained in this study. Of note, the RLS itself was not associated with the heart structure changes.

What does this mean? It means that patients with RLS on hemodialysis may need to be studied for PLMS. More studies will be needed though to find out if treating PLMS improves results.

Oral appliances for obstructive sleep apnea lower blood pressure

Oral appliances are a type of mouth guard worn at night when asleep to treat obstructive sleep apnea (OSA). I use them in patients with mild to moderate OSA, and in those with severe OSA but who don't respond to CPAP. OSA is strongly associated with high blood pressure (HTN), and CPAP has been shown to help reduce HTN by treating OSA. There have not been many studies showing that oral appliances reduce blood pressure when used to treat OSA. This paper pooled data from 7 studies that measured blood pressure changes in OSA patients using an oral appliance. The results showed that in those with mild to moderate OSA, an oral appliance modestly improved blood pressure, and results were comparable to CPAP.

CPAP use and high blood pressure.

It's well known that obstructive sleep apnea (OSA) is linked to high blood pressure (HTN). However, it's less clear that CPAP reduces HTN. In the October edition of Journal of clinical Sleep Medicine is a study attempting to show just that. Researchers studied veterans with known OSA who also had HTN and diabetes (DM). They monitored their CPAP use and followed them for upto one year.

Results showed that both systolic and diastolic blood pressure decreased significantly with CPAP use. This effect was most prominent with African-American patients, but still present in European-Americans. Interestingly, CPAP use did not reduce the subjects fasting blood sugar levels or long term blood sugar control as measured by their hemoglobin A1C.

Melatonin may improve sleep in patients taking beta-blockers

Beta blockers are a class of high blood pressure medications that have been around for decades. It is well known that beta blockers can disrupt sleep, possibly contribute to nightmares, and cause daytime fatigue. Beta blockers (along with non-steroidal anti-inflammatory medications) can reduce melatonin secretion, the hormone that is produced at night to help us sleep.

In the October edition of the Journal Sleep is a study about melatonin use in patients with high blood pressure on chronic beta blocker use. This study was a randomized, placebo controlled double blinded assessment. Patients' sleep was measured objectively in a sleep lab and at home for 3 weeks wtih actigraphy. Results showed statistically significant improvement in total sleep time, sleep efficiency, and onset to sleep with the melatonin in the sleep lab and at home. There was no sign of tolerance or side effects to the melatonin, or rebound sleep problems after stopping the melatonin.

These results are promising, as many patients need to take beta blockers for their long term cardiovascular health. Since this study was only three weeks long, we don't know the long term effects of melatonin use, so caution is warranted. Also, getting quality is difficult, since the FDA does not regulate the production of melatonin.

Poors sleep quality linked to high blood pressure

This article discusses research demonstrating a link between self-reported poor sleep quality and resistant high blood pressure (HTN) in women. The artcle does not discuss possible causes. I think the common factor may be obstructive sleep apnea (OSA), which is a known cause of poor sleep quality and is linked to HTN. Because the research did not ask about OSA, I would guess that many of the women have that condition. Since OSA is treatable, and a reversible contributor to HTN, men and women should talk to their doctor about poor sleep quality.

Insomnia Linked to High Blood Pressure

Here is an article about research that is going to be presented at next week's Sleep Meeting in Boston. It details how researchers have shown a link between insomnia and high blood pressure. It makes sense, as some insomniacs are thought to have chronically elevated nervous systems.

Deep Sleep, High Blood Pressure, and Elderly Men

There is an abstract in the journal Hypertension from August 2011 about the relationship between sleep stages and development of high blood pressure (a.k.a. HTN). There are three stages of sleep - light non-REM sleep, deep sleep, and REM (a.k.a. dream) sleep. Researchers studied 784 men greater than 64 years old who did not have HTN with an in-home sleep study. After a mean follow up of 3.4 years, 243 developed HTN. Analyses of the results demonstrated that developing HTN was associated with low oxygen levels, increased light non-REM sleep, and decreased deep sleep. After adjusting for age, nonwhite race, study site, and body mass index, only deep sleep was associated with developing HTN. The association was not reduced even after accounting for sleep duration, sleep fragmentation, and severity of sleep-disordered breathing (e.g. obstructive sleep apnea).

The researchers concluded that reduced deep sleep may contribute to adverse blood pressure in men. Unfortunately, the percentage of sleep that is deep sleep normally reduces with age in men and women. At the current moment, there is not a reliable way to increase deep sleep percentage without sleep deprivation or using medications.