Is obstructive sleep apnoea more than an epiphenomenon in patients with obesity? A cardiovascular perspective from a real-world propensity score-matched study

Background Obesity is the main risk factor for Obstructive Sleep Apnoea (OSA). Previous studies have shown that OSA affects ~50-70% of patients with obesity and exacerbates sympathetic activation, inflammation and endothelial dysfunction in these patients. However, it is still unclear whether OSA exacerbates cardiovascular (CV) events in patients with obesity. Purpose To test the hypothesis that OSA increases CV events in patients with obesity regardless of its grade. Methods We conducted a retrospective cohort analysis using the TriNetX Global Health Research Network through anonymised electronic medical records. We identified adult patients >40 years with obesity without previous anti-obesity therapy (GLP-1 agonists and tirzepatide) or bariatric surgery. We excluded patients with previous episodes of myocardial infarction and/or stroke. We used multiple code recommendations for tracking the presence of OSA, according to the international Classification of Diseases 10th edition: G47.33, G47.3, G47.39 or G47.30. We performed a propensity score matching in a 1:1 ratio for age, sex, ethnicity, hypertension, diabetes, dyslipidemia, smoking and chronic kidney disease. The combined endpoint included the incidence of 3-point MACE (non-fatal myocardial infarction, non-fatal stroke and all-cause mortality). Results In a crude analysis, patients with obesity+OSA represented approximately 15% of the sample. After the propensity score matching, 1,534,850 patients with obesity were included for the analysis (50% in each group: with and without OSA). After a median of 730 days of follow-up, OSA increased the incidence of combined events by 11% (OR:1.11; 95% CI: 1.09 – 1.13). A stratified analysis by different grades of obesity revealed that this result was driven by more severe classes of obesity: grade 1 (OR: 0.92; 95% CI: 0.85 – 1.00), grade 2 (OR: 1.06; 95% CI: 0.98 –1.17) and grade 3 (OR:1.08; 95% CI: 1.04 – 1.13). Conclusion OSA is associated with a modest increase in the incidence of MACE in patients with obesity. These results are probably attenuated by not capturing potential OSA underdiagnosis and OSA treatment in patients with obesity. Increasing OSA awareness in patients with obesity may be an interesting strategy for decreasing the cardiovascular burden associated with obesity in parallel to the improvement of sleep-related symptoms in these patients.