The driver of benefit appears to be the amount of weight lost at 10 years, but the surgery also likely eases OSA symptoms.
Patients with moderate-to-severe obstructive sleep apnea (OSA) and obesity who undergo bariatric surgery have significantly reduced risks of major adverse cardiovascular events and all-cause mortality when compared with those treated without surgery, the MOSAIC study shows.
The findings, which were published today in the Journal of the American College of Cardiology, suggest that intentional weight loss with bariatric surgery should be strongly considered for those with moderate-to-severe OSA, say investigators.
“Everything starts with obesity,” lead investigator Ali Aminian, MD (Cleveland Clinic, OH), told TCTMD. “Obesity is the driver of disease in the first place, and we showed that if we help them lose weight, people who have moderate-to-severe sleep apnea can significantly decrease their risk of dying, and significantly decrease their risk of cardiovascular events.”
Clinical guidelines for OSA recommend treatments that include positive airway pressure (PAP), oral devices, changing sleep positions, lifestyle modification with an emphasis on diet and physical activity, or surgery that involves removing tissue in the neck or jaw. While weight loss is advised for all obese patients with OSA, Aminian said there is less consideration given to bariatric surgery. In 2021, a scientific statement from the American Heart Association stated that bariatric surgery could be a treatment option for those with OSA-related comorbidity.
“In the future, the guidelines need to focus more on effective therapies for weight loss such as anti-obesity medications or bariatric surgery, not just lifestyle modification, to help people lose more weight,” he said. “Lifestyle modification is needed, but it’s not enough because the more weight lost, the greater the benefit.”
Nishant Shah, MD (Duke University Medical Center, Durham, NC), a preventive cardiologist who wasn’t involved in the study, said the results further support the urgency to aggressively battle obesity in the United States. There is accumulating evidence that cardiovascular events can be reduced when people are treated with the new anti-obesity medications, such as GLP-1 receptor agonists, and now these data supporting treatment with metabolic surgery. Recently, top-line findings from the SURMOUNT-OSA trials suggested that tirzepatide (Zepbound and Mounjaro; Eli Lily) may have significant benefits for patients with moderate-to-severe OSA.
“These results support the treatment of obesity in various settings,” Shah told TCTMD. “The results of the current study also shed light into the importance metabolic surgery may have on the improving not only OSA, but also cardiometabolic risk factors, MACE, and all-cause death in obese patients. Metabolic surgery referrals are often underutilized and earlier referrals for high-risk obese patients is critical.”
MOSAIC Results
OSA occurs with the complete or partial collapse of the upper airway and results in fragmented, disrupted sleep. It’s a common condition, affecting nearly 1 billion individuals worldwide, and moderate-to-severe OSA is strongly linked to excess weight and obesity, said Aminian. Bulky, fatty tissue in the neck can compress the airway while a person is laying down, and those with OSA usually wake up tired and have a poorer quality of life.
“With the hypoxia they have during the night, this increases the release of hormones and increases sympathetic tone, and that can increase blood pressure,” said Aminian. “It can also increase inflammation in the body. All of these—hypoxia, autonomic dysfunction, increase in blood pressure—are risk factors for cardiovascular disease.”
While OSA is typically treated with PAP to decrease symptoms, it doesn’t cure it and several trials have failed to show that PAP decreases the risk of MACE or mortality. Despite the strong association with obesity, it has been uncertain if intentional weight loss in patients with OSA can decrease the risk of cardiovascular outcomes. There have been no randomized trials to date.
MOSAIC was a retrospective cohort study of patients with obesity and moderate-to-severe OSA treated at the Cleveland Clinic Health System between 2004 and 2018. All patients were referred to clinic for bariatric surgery for weight loss. Moderate-to-severe OSA was defined as 15 or more events per hour based on polysomnography or a home sleep apnea test within 1 year of surgery. In total, 13,657 adults (mean age 52.0 years; 54.9% male) with obesity were included in the analysis, of whom 970 underwent bariatric surgery (either Roux-en-Y bypass or sleeve gastrectomy).
The researchers analyzed outcomes using overlap weighting and regression analysis, the latter a propensity-score method that attempts to mimic a randomized trial. With overlap weighting, patients are assigned weights proportional to the probability they would belong to the opposite treatment group, a method that ensures patient characteristics are balanced between two groups.
The cumulative incidence of MACE—a composite of coronary and cerebrovascular events, as well as heart failure (HF), atrial fibrillation (AF), and all-cause mortality—at 10 years was 27.0% in the surgical group versus 35.6% in the nonsurgical arm (adjusted HR 0.58; 95% CI 0.48-0.71). The results were consistent across various subgroups, with no heterogeneity seen for the primary endpoint based on sex, age, body mass index, race, smoking status, and other factors.
All-cause mortality at 10 years also was lower in the surgical group: 9.1% versus 12.5% (adjusted HR 0.63; 95% CI 0.45-0.89). Regarding other secondary endpoints, the risks of HF and coronary events were significantly lower in the surgical arm, but the incidence of cerebrovascular events and AF did not differ between groups.
At 10 years, patients treated with bariatric surgery lost approximately 33.2 kg compared with 6.6 kg for the control group. A decade after surgery, those treated with surgery had maintained a loss of 24.0% of their body weight versus 4.7% for those in the nonsurgical group.
Shah was impressed by the findings, calling it “as strong of an observational study as you can find,” but pointed out it is a single center study, which limits generalizability to other communities, countries, or health systems. “There also is residual confounding, even though the authors did an amazing job to limit it, in any observational study,” he said. “Thus, it is still important to have supporting data with randomized clinical trials that are multicentered with adjudicated hard endpoints.”
Weight Loss or Less Sleep Apnea?
To TCTMD, Aminian said this is the first study showing that bariatric surgery can lower the risk of cardiovascular events and improve survival in patients with obesity and OSA.
In a prior study, the researchers showed that Roux-en-Y bypass surgery was associated with greater weight loss, better diabetes control, and a lower risk of MACE in patients with obesity and type 2 diabetes. In 2020, a Swedish observational study found that bariatric surgery was associated with longer life expectancy when compared with usual care in patients with obesity. Cardiovascular and cancer mortality were also lower in those treated surgery.
The reductions in MACE and all-cause mortality with bariatric surgery seen in MOSAIC are likely attributable both to weight loss and treatment of OSA, said Aminian.
“It’s hard to differentiate,” he said. “Losing weight, all those cardiometabolic risk factors—blood pressure, cholesterol, hyperglycemia, diabetes, inflammation—are going to improve. So, there’s systemic effects, but at the same time, when fat goes away, including from around the neck area, the severity of sleep apnea is going to improve.” He noted that a small subset of patients had a repeat sleep study performed a few years after bariatric surgery. In this group, 58% had severe OSA at baseline, but this number declined to 13% after surgery.
When compared with the surgical patients, the 10-year incidence of MACE was higher in the subset of nonsurgical patients who lost less than 10% of their body weight (adjusted HR 0.45; 95% CI 0.36-0.57). There was no difference in MACE outcomes between the control group who lost more than 10% of their body weight and the bariatric surgery group.
“This supports the hypothesis that the amount weight loss maybe the biggest driver of benefit, independent of how it is lost,” said Shah. “However, multicentered randomized data will certainly make the hypothesis clearer if there remains any debate.”
With the introduction of GLP-1 receptor agonists for weight loss, Aminian suspects the results would be comparable. “It’s the weight loss itself that’s important,” he said. “It doesn’t matter how they get to that weight loss, or how they lose weight, they’re going to see the benefits.”