To our knowledge, this research is the first study to explore the prevalence of OSAHS in patients with MINOCA and demonstrate the possible relationship between OSAHS and clinical outcomes in this population. In this cohort of 583 patients with MINOCA, the prevalence of OSAHS was 27.1%, similar to other CAD population. We observed that OSAHS was associated with an increased risk of all-cause mortality and MACCE comprising cardiac death, nonfatal myocardial infarction, HF, cardiovascular-related rehospitalization, and stroke. After adjusting for demographics, cardiovascular risk factors, and discharge medications, patients with OSAHS exhibited 1.714 times risk of all-cause mortality and 1.787 times risk of MACCE at three-year follow-up.
The previous large multi-center registry, The Sleep and Stent Study11 has shown that obstructive sleep apnea is independently associated with cardiovascular adverse events in patients with CAD, with the prevalence reaching 45.3%. A similar study conducted by Lee also has reported that sleep apnea prevalence is as high as 65.7% in patients admitted with AMI.12 However, the prevalence of OSAHS in patients with MINOCA is unknown. Although the identical diagnostic criterion of OSAHS was an AHI ≥ 15 in the present study, OSAHS was found in 27.1% of patients with MINOCA, which is relatively lower compared with that of CAD patients described by previous studies. In addition, we observed that only 70.9% of the individuals with OSAHS were classified as high risk by the Berlin Questionnaire. The results suggested that the sensitivity and specificity of Berlin Questionnaire remained controversial.
OSAHS is characterized by intermittent upper airway collapse with paradoxical thoracoabdominal movement during sleep, resulting in biochemical and haemodynamic disorders, including sympathetic activation, increased platelet agreeability, hypercoagulability, ultra-inflammation responses, endothelial dysfunction, increased pulmonary vascular resistance, and increased left ventricular load caused by decrease in intrathoracic pressure.27–31 These potential mechanisms together contribute to the progression of atherosclerosis, myocardial infarction, hypertension, arrhythmia, HF, and stroke.8 In the study of Mooe et al., the co-existence of CAD and sleep apnea resulted in 70% relative increase and a 10.7% absolute increase in the composite of death, cerebrovascular events, and myocardial infarction after a median period of 5.1-year follow-up.32 In one study, obstructive sleep apnea was demonstrated as an independent predictor for clinical outcomes in patients with acute coronary syndrome after PCI.33 The main finding of our observational study is that OSAHS is independently associated with all-cause mortality and MACCE in patients with MINOCA. The total-cause mortality of MINOCA in the three-year follow-up was 11.8% in the present study, agreeing with the SWEDEHEART registry, with a mortality of 13.4% after mean follow-up of 4.1 years.34 OSAHS patients had an adjusted OR of 1.787 for the MACCE when compared with patients without sleep apnea. Interestingly, we observed that stroke accounted for one-fifth of MACCE in the current study, 16 in patients with OSAHS and 7 in the control group, which is consistent with previous findings indicating OSAHS as an independent risk factor for stroke.13, 35–36
The design of present study has certain strengths. First, all patients with OSAHS were diagnosed with gold standard by supervised polysomnography during hospitalization. Second, we strictly excluded clinically overt causes for a myocardial injury, such as myocarditis, sepsis, pulmonary embolism, Takotsubo syndrome, an potentially overlooked obstructive CAD from the current study, consistent with the clinical algorithm for the recently introduced diagnosis of MINOCA by AHA.4 Thus, the definition of MINOCA utilized in the current study is in accordance with the statement of contemporary diagnosis and management of patients with MINOCA, thereby further supporting our results. Third, the well-known confounding risk and preventive factors that affect clinical outcomes in patients with MINOCA, such as traditional cardiovascular risk factors, STEMI, RAAS inhibitors, and statins, were all analyzed for adjustment. Fourthly, the rate of loss to follow-up was low in the present study owing to the convenient instant messaging app (WeChat).
Several limitations need to be considered in the present study. First, the present study is an observational single Chest Pain Center study, and the results may not be generalizable. Second, the sample size of the current study is relatively small due to the critical inclusion and exclusion criteria. Third, the exclusion of patients who refused to participate in the trial and loss of follow-up could contribute to a bias of the results in present study.