BackgroundStandard modifiable risk factors (SMuRFs) increase the risk of cardiovascular events in patients with acute coronary syndrome (ACS) and are also strongly associated with obstructive sleep apnea (OSA) in a bidirectional relationship. However, the association of OSA with recurrent cardiovascular events in ACS patients based on the number of SMuRFs remains unclear. Hence, we aimed to elucidate the prognostic implication of OSA in ACS patients stratified by the number of SMuRFs.MethodsThis was a post hoc analysis of the OSA-ACS study (NCT03362385), including 1927 patients admitted for ACS and undergoing portable sleep monitoring. OSA was defined as an apnea hypopnea index ≥ 15 events/h. The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE) including cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina or heart failure, and ischemia-driven revascularization. Cox proportional hazards model and Kaplan-Meier analysis were used to investigated the relationship between OSA and subsequent cardiovascular events after patients were stratified by the number of SMuRFs.ResultsAmong 1927 patients enrolled, 130 (6.7%) had no SMuRF, 1264 (65.6%) exhibited 1–2 SMuRFs and 533 (27.7%) presented 3–4 SMuRFs. With the increase of the number of SMuRFs, the proportion of OSA in ACS patients tended to increase (47.7% vs. 51.5% vs. 56.6%), but there was no significant difference between them (P = 0.08). After the stratification of ACS patients via SMuRF numbers and adjustment for confounding factors, fully adjusted Cox regression indicated that OSA increased the risk of MACCE (adjusted HR, 1.65; 95%CI, 1.06–2.57; P = 0.026) and ischemia-driven revascularization (adjusted HR, 2.18; 95%CI, 1.03–4.65; P = 0.042) in ACS patients with 3–4 SMuRFs.ConclusionsIn hospitalized ACS patients, OSA is associated with an increased risk of MACCE and ischemia-driven revascularization among patients with 3–4 SMuRFs. Therefore, screening for OSA should be emphasized in ACS patients with 3–4 SMuRFs, and intervention trials should be prioritized in these high-risk patients.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11239-023-02830-w.