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Metabolic surgery became the first therapy associated with a reduction in incident cardiovascular disease and death among patients with obesity and obstructive sleep apnea (OSA), based on a retrospective cohort study.

Such patients who received metabolic surgery, also known as bariatric surgery, had a significantly lower cumulative risk of subsequent major adverse cardiovascular events (MACE) over a median follow-up of 5.3 years (27% vs 35.6% for a non-surgical control group; adjusted HR 0.58, 95% CI 0.48-0.71), reported Steven Nissen, MD, of the Cleveland Clinic, and coauthors.

All-cause mortality alone also significantly favored the patients who had undergone metabolic surgery (9.1% vs 12.5%; adjusted HR 0.63, 95% CI 0.45-0.89), as did heart failure (HR 0.30, 95% CI 0.21-0.45) and coronary artery events (HR 0.65, 95% CI 0.43-0.99), according to the MOSAIC study published in the .

The study authors said their findings support recommending weight loss and lifestyle modifications in the absence of approved pharmacological therapies. "However, rather than focusing on lifestyle modification alone, treating obesity with more effective and durable methods may be required to improve cardiovascular outcomes and survival in patients with OSA and obesity," they argued.

"Before the MOSAIC study, no therapy had been shown to reduce the risk of [MACE] and death in patients with sleep apnea," Nissen stressed .

MACE, the study's primary endpoint, was defined as first occurrence of coronary artery events (unstable angina, myocardial infarction, coronary intervention/surgery), cerebrovascular events (ischemic or hemorrhagic stroke, carotid intervention/surgery), heart failure, atrial fibrillation, and all-cause mortality.

Metabolic surgery was not associated with any reductions in cerebrovascular events and atrial fibrillation as individual endpoints.

However, in the subset of patients who had been administered a repeat sleep study, those who received metabolic surgery had significant improvements in their OSA severity and hypoxemia, Nissen's group reported.

OSA is fairly common and especially prevalent among patients with obesity. The condition causes excessive daytime sleepiness and generalized fatigue; symptoms can be managed by positive airway pressure (PAP), oral appliances, and neurostimulation implants already on the market.

Whether weight loss can reduce the risk of MACE or death in this setting was a key question in MOSAIC.

Nissen and colleagues reported that the patients who received metabolic surgery lost an average of 33.2 kg (73.2 lb) after 10 years, while patients assigned to the nonsurgical control group lost 6.64 kg (14.6 lb). Average body weight was reduced by 24% and 4.7%, respectively (P<0.001).

In both surgical and nonsurgical patients who had managed to lose more than 10% of their body weight, MACE rates were similar over follow-up (adjusted HR 0.85, 95% CI 0.67-1.08).

"The MOSAIC study suggests the presence of a dose-dependent response between the amount of weight loss and cardiovascular benefits in patients with obstructive sleep apnea; the greater the weight loss, the lower the risk of heart complications," said study coauthor Ali Aminian, MD, also of the Cleveland Clinic, in a statement.

"With emergence of a new generation of obesity medications that can provide an average weight loss in the range of 15-20%, similar findings are theoretically possible from medical therapies," Aminian added.

Indeed, recent data show that tirzepatide (Zepbound) injections reduced sleep apnea severity among patients with obesity, regardless of PAP use. Tirzepatide, a combination GLP-1 and GIP receptor agonist, had won an indication for adult chronic weight management late last year.

The MOSAIC study relied on electronic health record data taken from the Cleveland Clinic Health System (CCHS).

Participants were adult patients who met criteria for both obesity (BMI of 35-70) and moderate-to-severe OSA (Apnea Hypopnea Index [AHI] of 15 or more events per hour or a Respiratory Event Index [REI] of 15 or more events per hour). Exclusion criteria included cancer diagnosis closely preceding metabolic surgery, prior organ transplant, and severely reduced left ventricular ejection fractions.

The metabolic surgery group (n=970) received either a Roux-en-Y gastric bypass or sleeve gastrectomy at the Ohio or Florida CCHS hospitals in 2004-2018. The comparison arm, the nonsurgical controls (n=12,687), were chosen randomly to match the time intervals between date of sleep study and date of surgery in the surgical group.

In this observational study, investigators addressed confounding by overlap weighting, a propensity score method.

They ended up with a total cohort that had 63.3% women, an average age of 48.6 years, and a median BMI of about 46. Around 60% of both surgical and control arms had AHI or REI events of 30 or more per hour at baseline (median 37-38). White patients made up 71.1% of the patient population, and Black patients made up 22.5%. Prevalent comorbidities included hypertension (75.5%), dyslipidemia (61-65%), and type 2 diabetes (22.3%). With regard to smoking status, 54.2% of patients had never smoked, 39.6% were former smokers, and 6.2% were current smokers.

Researchers cited the relatively short follow-up period as a limitation of the study. Additionally, they did not have information on PAP adherence and specific causes of death. Findings may also lack generalizability to healthcare systems outside the CCHS and were subject to potential coding errors.

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