CPAP Benefits BP on Top of Weight Loss in Sleep Apnea

June 12, 2014

Two new studies have shed more light on the role of continuous positive airway pressure (CPAP) on cardiovascular risk in patients with sleep apnea.

One study shows that in obese patients with moderate to severe sleep apnea, weight loss is the most important intervention and reduces inflammation, insulin resistance, dyslipidemia, and blood pressure. But CPAP had a meaningful incremental effect on blood pressure in fully adherent patients when used in addition to weight loss.

The second study provides more evidence that CPAP is effective for lowering blood pressure in patients with moderate to severe sleep apnea, even those with blood pressures in the normal range. But the study found no evidence of benefit of nocturnal oxygen supplementation on blood pressure in these patients.

Both studies are published in the June 12 issue of the New England Journal of Medicine.

"We found that in patients with obesity and moderate to severe sleep apnea, it is the obesity rather than the sleep apnea that is the major cause of inflammation, insulin resistance, dyslipidemia, and raised blood pressure," lead author of the first study, Julio Chirinos, MD, Philadelphia Veterans Affairs Medical Center, Pennsylvania, commented to Medscape Medical News.

"But sleep apnea does appear to have some effect on blood pressure," he noted. "Our message is that if sleep apnea patients are obese — which many of them are — they need to deal with their obesity as the first priority. But CPAP is also useful in reducing blood pressure in these patients."

Lead author of the second paper, Daniel Gottlieb, MD, Veterans Affairs Boston Healthcare System, added: "Prior studies have shown that CPAP reduced blood pressure in sleep apnea patients with poorly controlled blood pressures, but our results extend these findings to patients in the normal range. The amount of blood pressure reduction we found with CPAP in this study would translate into a 20% reduction in stroke and a 15% reduction in cardiovascular disease."

In an accompanying editorial, Robert C. Basner, MD, Columbia University College of Physicians and Surgeons, New York, points out that the results were still relevant in patients who did not have "subjective" sleepiness.

He adds, "These 2 studies task us to design larger, and longer, trials...to comprehensively address the explicit, implicit, and complicit treatment imperatives of obstructive sleep apnea and cardiovascular health."

Weight Loss First Priority

On the study comparing weight loss and CPAP with both interventions, Dr. Chirinos explained that while many observational studies have suggested CPAP is associated with a reduction of inflammation, insulin resistance, and dyslipidemia, there haven't been any randomized controlled trials.

"The problem is that sleep apnea and obesity often coexist and until now nobody has dissected the relative contribution of each one," he pointed out. "So we looked at weight loss alone, CPAP alone, and both together."

For the study, 181 patients with obesity, moderate-to-severe obstructive sleep apnea, and serum levels of C-reactive protein (CRP) greater than 1.0 mg/L were randomly assigned to CPAP, a weight-loss intervention, or both for 24 weeks.

Among the 146 participants for whom there were follow-up data, those assigned to weight loss only and those assigned to the combined interventions had reductions in CRP levels, insulin resistance, and serum triglyceride levels. None of these changes were observed in the group receiving CPAP alone, and there were no significant incremental effects in the combination group vs the weight loss–only group.

Blood pressure was reduced in all 3 groups. In per protocol analyses, which included 90 participants who met prespecified criteria for adherence, the combined interventions resulted in a larger reduction in systolic blood pressure and mean arterial pressure than did either CPAP or weight loss alone.

Table 1. Effect of CPAP/Weight Loss on Blood Pressure: Per Protocol Analysis of Adherent Patients

Endpoint Weight Loss CPAP Combination
Reduction in blood pressure (mmHg) 6.8 3.0 14.1

 

Dr. Chirinos commented to Medscape Medical News: "Obesity appears to be responsible for most of the problems associated with sleep apnea, but by correcting sleep apnea with CPAP this will have an incremental effect on blood pressure."

He explained that correcting sleep apnea has other, more obvious benefits too. "Sleep apnea is responsible for poor quality of life in that patients do not get a full night's sleep and therefore are tired during the day, and often fall asleep. This can obviously have disastrous consequences, such as car accidents. But sleep apnea also seems to have an effect on the cardiovascular system — probably mediated by raised blood pressure, and our study confirms this."

He pointed out that the current results apply only to obese patients. "In lean patients we don't know if CPAP is associated with reduced cardiovascular outcomes. But CPAP is still indicated for lean patients with sleep apnea to reduce the symptoms of daytime sleepiness."

CPAP vs Oxygen

For the second study, 318 patients with moderate to severe sleep apnea were randomly assigned to receive education on sleep hygiene and healthy lifestyle alone (the control group) or, in addition to education, either CPAP or nocturnal supplemental oxygen.

In the 281 who had ambulatory blood pressure measurements at follow-up, the 24-hour mean arterial pressure (primary endpoint) at 12 weeks was lower in the group receiving CPAP than in the control group or the group receiving supplemental oxygen.

Table 2. Effect of CPAP vs Oxygen on Blood Pressure in Sleep Apnea

Endpoint CPAP vs Control Oxygen vs Control CPAP vs Oxygen
Difference in mean arterial pressure at 12 weeks (mmHg) –2.4 (P = .04) 0.4 (P = .71) –2.8 (P = .02)

 

Dr. Gottlieb noted that most people with sleep apnea have other risk factors for cardiovascular disease — most commonly obesity — but even after adjustment for these other risk factors, patients with sleep apnea still have a 3-fold increased risk for myocardial infarction and stroke.

He explained that in patients with sleep apnea the airway collapses during sleep, resulting in a reduction in oxygen levels and a rise in CO2 levels and a brief period of arousal, of which the patient may not be aware.

This leads to a rise in blood pressure, increased inflammation in the blood vessels, and worsening of glucose tolerance. These effects are thought to be mediated by activation of the sympathetic nervous system.

Oxygen Not Necessary

"Because many people do not comply with CPAP, we tested whether giving supplemental oxygen at night would have a similar beneficial effect. But we found that while nocturnal oxygen improved oxygenation of the blood like CPAP does, it does not lead to a reduction in blood pressure," Dr. Gottlieb said. "So our recommendation is that oxygen supplementation is not necessary for most patients with sleep apnea. There may be some patients that still might want to use it. We excluded the most severe patients from this study so it may still be relevant for them, but there is no data."

However, CPAP did lead to a reduction in blood pressure even in patients within normal range or those whose blood pressure is already well controlled with medication, he noted. "And that reduction in blood pressure will be beneficial in terms of reducing risk of cardiovascular disease and stroke. It has been shown that reducing blood pressure is still beneficial right down to 110/70."

He pointed out that the blood pressure effect of CPAP is greater at night because sleep apnea increases blood pressure acutely at night. Patients are often unaware of this unless they have 24-hour blood pressure monitoring.

"CPAP restores the normal fall in blood pressure that occurs at night," he added. "And we know that increased blood pressure at night has a worse effect on cardiovascular risk."

Still Relevant With Low Adherence, Mild Symptoms

The researchers note that because patients were recruited from general cardiology practices rather than from sleep centers, they tended to have only mild symptoms of obstructive sleep apnea. Adherence to treatment with CPAP was somewhat lower (fewer hours of nightly use) than that reported in some previous studies.

The fact that there was still a benefit may be relevant to public policy, given that reimbursement is often restricted to patients whose adherence exceeds a specified threshold.

Dr. Gottlieb pointed out that the current study was restricted to moderate to severe sleep apnea. "At present we don't have evidence for benefit on blood pressure of CPAP for patients with mild sleep apnea. For these patients the main recommendations are still weight reduction and alcohol reduction." He explained that alcohol relaxes the muscles in the throat, which makes sleep apnea worse. "So our advice to all sleep apnea patients is 'eat less, drink less alcohol, and exercise more.'"

Moderate sleep apnea is defined as more than 15 events per hour where there is partial or complete collapse of the airway. It is very common, occurring in 4% of women and 9% of men, he said.

"The most common symptoms are unrefreshing sleep and snoring, although of course not everyone who snores has sleep apnea," he noted. "Many patients do not realize they have it. But if their spouse notices they are having episodes of stopping breathing in the night then they should have a prompt evaluation."

He added that the only way to definitely diagnose sleep apnea is by a sleep test, but this does not have to be a sleep lab. "There are now simple devices that can be used at home for this purpose. Once patients are diagnosed with sleep apnea they tend to have it for life unless they make some changes, such as losing weight. Then they may want to have a repeat sleep test to document resolution."

Dr. Gottlieb agreed with Dr. Chirinos' conclusion that weight loss should be the first-line treatment. "But CPAP is a useful addition. It is not an alternative to weight loss; rather, it is an adjunctive therapy. I wouldn't withhold CPAP while patients are trying to lose weight. They should do both. But maybe once they have lost weight they might not need CPAP anymore."

The study by Chirinos and colleagues was supported by grants from the National Heart, Lung, and Blood Institute. The study by Gottlieb and colleagues was supported by the National Heart, Lung, and Blood Institute and by a grant from the National Center for Research Resources. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

N Engl J Med. 2014;370:2265-2275, 2276-2285, 2339-2341. Chirinos Abstract  Gottlieb Abstract  Editorial

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