o tackle the cardiovascular risks from obstructive sleep apnea, continuous positive airway pressure (CPAP) was better than giving oxygen at night, and adding a weight-loss strategy may be even better in some respects for obese patients.
CPAP cut 24-hour mean arterial blood pressure by 2.8 mm Hg more than did supplemental oxygen at night (P=0.02) in a high-cardiovascular-risk population, Daniel J. Gottlieb, MD, MPH, of Brigham and Women's Hospital in Boston, and colleagues found in the HeartBEAT trial.
In a second trial of obese patients with elevated C-reactive protein (CRP) levels, CPAP came out similar to a weight-loss intervention or the combination of the two for reducing that inflammatory marker.
But CPAP plus weight management brought down insulin resistance, triglycerides, and blood pressure best, Julio A. Chirinos, MD, PhD, of the University of Pennsylvania in Philadelphia, and colleagues reported.
Both National Heart, Lung and Blood Institute-sponsored trials appeared in the June 12 issue of the New England Journal of Medicine.
Despite some substantial limitations, the findings are meaningful for practice, Robert C. Basner, MD, of Columbia University in New York City, wrote in an accompanying editorial.
"First, in obese patients with moderate-to-severe obstructive sleep apnea, the use of CPAP alone, but not oxygen supplementation alone, during sleep may ameliorate systemic hypertension and cardiovascular risk, even in patients treated for hypertension and cardiovascular risk who did not have 'subjective' sleepiness," he wrote.
"Second, weight loss may decrease cardiovascular morbidity and risk when CPAP is prescribed for these patients," he added.
Kingman Strohl, MD, clinical director of sleep medicine at University Hospitals Case Medical Center in Cleveland, agreed.
"While this has been shown in epidemiologic studies, these interventional studies bring to our evidence-based medicine the limitations as well as the strengths of treatments we have in this common disorder," he told MedPage Today.
Oxygen Versus CPAP
The HeartBEAT trial included 318 patients with cardiovascular disease or multiple cardiovascular risk factors recruited from cardiology practices and an apnea-hypopnea index (AHI) of 15 to 50 events per hour, diagnosed with home sleep testing after a positive screen with the Berlin questionnaire.
They were randomized to education on sleep hygiene and healthy lifestyle alone or with CPAP or nocturnal supplemental oxygen.
Whereas both treatments reduced nocturnal hypoxemia to a similar degree, the primary endpoint of 24-hour mean arterial pressure didn't show any benefit from supplemental oxygen compared with controls. By contrast, Basner called the impact of CPAP on blood pressure clinically significant, at -2.8 mm Hg versus supplemental oxygen at 12 weeks (P=0.02).
Notably, CPAP had an even bigger differential benefit for nighttime blood pressure than for daytime blood pressure, which Basner noted was of particular interest "given that blood pressure during sleep may be a particularly strong marker of cardiovascular outcomes."
Nocturnal systolic blood pressure fell 0.93 mm Hg for each additional hour of CPAP use per night (P=0.03).
"The temptation to use something like oxygen for the treatment of sleep apnea should probably be resisted because CPAP probably does more than just improve oxygenation," Strohl added. "It improves the cardiovascular performance and it reduces the driving pressure for blood pressure, which are intrathoracic pressure changes that occur with obstructive apnea."
Weight Loss Versus CPAP
The trial by Chirinos and colleagues included 181 obese patients with moderate-to-severe obstructive sleep apnea (an AHI of at least 15 events per hour as screened by home sleep testing and confirmed by lab testing) and serum CRP levels greater than 1.0 mg/L.
They were randomized to treatment with CPAP; a weight-loss intervention with weekly individual counseling, exercise targets, and liquid meal replacements to meet calorie targets; or both interventions for 24 weeks.
The average weight loss came out similar in the two groups targeting weight, at about 15 lbs., whereas the CPAP group didn't change discernibly.
CRP reductions, the primary endpoint, dropped significantly only in the groups that included weight management (P<0.01 to P<0.001) but weren't incrementally greater with the combination approach versus either other group in the modified intention-to-treat or the per-protocol populations.
Insulin resistance and triglycerides at 24 weeks largely followed the same pattern, although both were significantly more impacted in the combined-intervention group than with CPAP (P=0.046 to P<0.001).
Blood pressure dropped across groups.
But in the per-protocol subgroup -- 90 people who lost at least 5% of their baseline weight and used CPAP for at least 4 hours a night on at least 70% of nights, the combined strategy cut systolic blood pressure and mean arterial pressure compared with either intervention alone.
That impact amounted to a more than 10 mm Hg decrease compared with CPAP alone and a more than 5 mm Hg decrease compared with weight loss alone (P<0.001 and P=0.02).
"Our findings suggest that both obstructive sleep apnea and obesity have an independent causal relation to hypertension," the researchers concluded.
However, Strohl cautioned that 24 weeks may not have been long enough to definitively compare the strategies.
"The effect of CPAP may not be apparent until greater than 6 months, so longer-term trials are needed," he told MedPage Today.
In the HeartBEAT trial, CPAP use was fairly low and there were issues with the handling of CRP, Basner cautioned.
"The assays and statistical handling of CRP values, which were skewed and had large ranges at baseline, were unlike those of previous investigators, whose results informed the current study design and data interpretation," he wrote.
Also, "the variability of the CRP level within the same participant and the validity of the CRP level as an independent measure of cardiovascular risk, particularly in patients receiving statin therapy, also raise concerns," he added.
Both studies lacked any comprehensive analysis of the severity of sleep-disordered breathing after treatment, which "hampers the interpretation of complicit interactions among breathing, blood pressure, the control of metabolic and inflammatory markers (e.g., CRP level, leptin level, and extent of insulin resistance), and sleepiness," Basner noted.
From the American Heart Association:
Both studies were funded by the National Heart, Lung and Blood Institute (NHLBI), with additional funding from the National Center for Research Resources for the HeartBEAT study.
Chirinos disclosed relationships with the NHLBI.
Gottlieb disclosed relationships with the NHLBI, Philips-Respironics, and ResMed.
Basner disclosed being a member of the data and safety monitoring board for Chirinos's study.
Strohl disclosed relationships with Inspire, the NIH, and the Department of Veterans Affairs.