Prognostic implications of obstructive sleep apnea in patients with unstable angina stratified by remnant cholesterol and triglyceride: a prospective cohort study.

BACKGROUND: The prognostic significance of obstructive sleep apnea (OSA) in patients with unstable angina (UA) based on remnant cholesterol (RC) or triglyceride (TG) levels remains unclear. This study aims to evaluate the effects of the interaction between RC, TG, and OSA on cardiovascular outcomes in UA patients. METHODS: In this prospective cohort study, OSA was diagnosed when apnea-hypopnea index of ≥ 15 events/h. Patients with high RC (HRC, n = 370) or high TG (HTG, n = 362) included RC or TG in the highest tertile, and those in the middle and lowest tertiles were defined as normal RC (NRC, n = 736) or normal TG (NTG, n = 744). The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including cardiovascular death, myocardial infarction, ischemia stroke, ischemia-driven revascularization, or hospitalization for UA. RESULTS: A total of 1,106 eligible UA patients were enrolled, among which 560 (50.6%) had OSA. RC and TG levels were increased in OSA patients, but there was no difference in the prevalence of OSA between the NRC and HRC or NTG and HTG groups. During a median follow-up of 1.9 (1.1, 3.0) years, OSA was associated with an increased risk of MACCE occurrence compared to non-OSA in UA patients with HRC (adjusted HR 2.06; 95% CI 1.20-3.51, P = 0.008), but not in those with NRC (adjusted HR 1.21; 95% CI 0.84-1.75, P = 0.297). The incremental risk in HRC was attributable to higher rates of hospitalization for UA and ischemia-driven revascularization. Results for HTG and NTG were similar. CONCLUSION: OSA was associated with a worse prognosis in UA patients with HRC or HTG, emphasizing the necessity of identifying OSA presence in this population. TRIAL REGISTRATION: Clinicaltrials.gov; No: NCT03362385.

Association of obstructive sleep apnoea with cardiovascular events in women and men with acute coronary syndrome.

BACKGROUND: The impact of sex on the association of obstructive sleep apnoea (OSA) with recurrent cardiovascular events following acute coronary syndrome (ACS) remains uncertain. This study sought to examine the association between OSA and long-term cardiovascular outcomes in women and men with ACS. METHODS: In this prospective cohort study, we recruited 2160 ACS patients undergoing portable sleep monitoring between June 2015 and January 2020. The primary end-point was major adverse cardiovascular and cerebrovascular event (MACCE), including cardiovascular death, myocardial infarction, stroke, ischaemia-driven revascularisation or hospitalisation for unstable angina or heart failure. RESULTS: After exclusion of patients with failed sleep studies, central sleep apnoea, regular continuous positive airway pressure therapy and loss of follow-up, 1927 patients were enrolled. Among them, 298 (15.5%) were women and 1014 (52.6%) had OSA (apnoea-hypopnoea index ≥15 events·h-1). The prevalence of OSA was 43.0% and 54.4% in women and men, respectively. In 4339 person-years (median 2.9 years, interquartile range 1.5-3.6 years), the cumulative incidence of MACCE was significantly higher in OSA versus non-OSA groups in the overall population (22.4% versus 17.7%; adjusted hazard ratio (HR) 1.29, 95% CI 1.04-1.59; p=0.018). OSA was associated with greater risk of MACCE in women (28.1% versus 18.8%; adjusted HR 1.68, 95% CI 1.02-2.78; p=0.042), but not in men (21.6% versus 17.5%; adjusted HR 1.22, 95% CI 0.96-1.54; p=0.10). No significant interaction was noted between sex and OSA for MACCE (interaction p=0.32). The incremental risk in women was attributable to higher rates of hospitalisation for unstable angina and ischaemia-driven revascularisation. CONCLUSIONS: In hospitalised ACS patients, OSA was associated with increased risk of subsequent events, particularly among women. Female patients with ACS should not be neglected for OSA screening and dedicated intervention studies focusing on women with ACS and comorbid OSA should be prioritised.

Prognostic implications of obstructive sleep apnea in patients with acute coronary syndrome stratified by homocysteine level: a prospective cohort study.

BACKGROUND: Sporadic studies have examined the impact of OSA on ACS patients by homocysteine (Hcy) level. This study attempted to comprehensively evaluate the effects of the interaction between Hcy and OSA on long-term cardiovascular outcomes in ACS patients. METHODS: In this prospective, large-scale cohort study, 2160 patients admitted for ACS were recruited to undergo overnight sleep monitoring. OSA was diagnosed when apnea-hypopnea index ≥ 15 events/h. Patients with normohomocysteinemia (NHcy) were defined as having serum Hcy ≤ 15 µmol/L, and the others had hyperhomocysteinemia (HHcy). The primary endpoint was major adverse cerebrocardiovascular event (MACCE), a composite of cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization and hospitalization for unstable angina and heart failure. RESULTS: A total of 1553 eligible ACS patients (average age: 56.3 ± 10.5 years) were enrolled, among which 819 (52.7%) had OSA, and 988 (63.6%) were with NHcy. OSA did not significantly affect the level of Hcy. During a median follow-up of 2.9 (1.6, 3.5) years, after adjustment for clinical confounders, OSA was associated with increased risk for MACCE occurrence versus non-OSA ones in ACS patients with NHcy (adjusted hazard ratio [HR] = 1.36, 95% confidence interval [CI] 1.02-1.83, P = 0.039), but not in those with HHcy (adjusted HR = 0.92, 95%CI 0.62-1.36, P = 0.668). There was an absence of interaction between homocysteine level and OSA in relation to MACCE (interaction P = 0.106). CONCLUSIONS: OSA was independently associated with worse prognosis in ACS patients with NHcy. Our study emphasized the necessity to identify potential presence of OSA in such a population. TRIAL REGISTRATION: ClinicalTrials.gov; Number: NCT03362385; URL: www. CLINICALTRIALS: gov .

Clinical outcomes of obstructive sleep apnea in patients with acute coronary syndrome in relation to hyperuricemia status.

The clinical outcome of obstructive sleep apnea in patients with acute coronary syndrome in relation to hyperuricemia is still unclear. We aimed to explore the clinical prognosis of obstructive sleep apnea in patients with acute coronary syndrome in relation to hyperuricemia status. This was a prospective cohort study. We included consecutively eligible patients with acute coronary syndrome who underwent cardiorespiratory polygraphy between June 2015 and January 2020. According to apnea-hypopnea index ≥ 15 events per hr and serum uric acid level, the population was divided into four groups: hyperuricemia with obstructive sleep apnea; hyperuricemia with non-obstructive sleep apnea; no hyperuricemia with obstructive sleep apnea; and no hyperuricemia with non-obstructive sleep apnea. The primary endpoint was major adverse cardiovascular and cerebrovascular events, including cardiovascular death, myocardial infarction, stroke, ischaemia-driven revascularization, and readmission for unstable angina or heart failure. Spearman correlation analysis and Cox regression model were mainly used to estimate the data. The median follow-up was 2.9 years. Among 1925 patients with acute coronary syndrome, 29.6% had hyperuricemia and 52.6% had obstructive sleep apnea. Uric acid was negatively correlated with minimum arterial oxygen saturation and mean arterial oxygen saturation, and positively correlated with apnea-hypopnea index, oxygen desaturation index and the duration of time with arterial oxygen saturation < 90% (p < 0.001). During 2.9 (1.5, 3.6) years of follow-up, obstructive sleep apnea was associated with an increased risk of major adverse cardiovascular and cerebrovascular events in patients with hyperuricemia (23.5% versus 13.4%; adjusted hazard ratio: 1.834; 95% confidence interval: 1.192-2.821, p = 0.006), but not in patients without hyperuricemia (21.9% versus 19.2%; adjusted hazard ratio: 1.131; 95% confidence interval: 0.880-1.453, p = 0.336). There was a correlation between uric acid levels and sleep respiratory indicators. Obstructive sleep apnea was associated with increased risk of major adverse cardiovascular and cerebrovascular events in patients with acute coronary syndrome with hyperuricemia, but not in patients without hyperuricemia.

Association Between Obstructive Sleep Apnea and Cardiovascular Events in Acute Coronary Syndrome Patients With or Without Revascularization　- A Prospective Cohort Study.

BACKGROUND: The effects of obstructive sleep apnea (OSA) on the prognosis of acute coronary syndrome (ACS) without revascularization remain unclear, so the aim of the present study was to elucidate the association of OSA with subsequent cardiovascular events in ACS patients with and without revascularization.Methods and Results: We prospectively recruited hospitalized ACS patients undergoing sleep monitoring between June 2015 and January 2020. OSA was defined as an apnea-hypopnea index ≥15 events/h. The primary endpoint was a major adverse cardiovascular and cerebrovascular event (MACCE), including cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization, or hospitalization for unstable angina or heart failure. Among 1,927 patients, 52.6% had OSA and 69.4% underwent revascularization. During a 2.9-year follow-up (1.5-3.6 years), the risk of MACCE was similar in patients with or without revascularization. OSA was an independent predictor of MACCE in the non-revascularization group (22.6% vs. 14.6%; hazard ratio (HR) 1.861; 95% confidence interval (CI) 1.239-2.796; P=0.003) but not in revascularization group (22.3% vs. 19.3%; HR 1.135; 95% CI 0.882-1.460; P=0.324). The incremental risk in the non-revascularization group was attributable to more hospitalizations for unstable angina (14.2% vs. 8.6%; HR 1.896; 95% CI 1.124-3.199; P=0.016). CONCLUSIONS: For patients with ACS, OSA was independently associated with higher risk of recurrent cardiovascular events among patients without revascularization but not among patients undergoing revascularization. The benefits of suitable OSA treatment for patients without revascularization need further investigation.

The impact of obstructive sleep apnea and comorbidity status on cardiovascular outcomes in patients with acute coronary syndrome.

BACKGROUND AND AIMS: The association of comorbidities on the prognosis of patients with acute coronary syndrome (ACS) was well documented. However, the impact of obstructive sleep apnea (OSA) on this association has been less studied. METHODS AND RESULTS: Between June 2015 to Jan 2020, we included consecutively eligible patients with ACS who underwent cardiorespiratory polygraphy. The definition of OSA was apnea-hypopnea index (AHI) ≥15 events/hour. Charlson Comorbidity Index (CCI) was used to evaluate the comorbidities. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization, and hospitalization for unstable angina or heart failure. In the 1927 ACS patients, 1014 (52.6%) had OSA. The prevalence of the mild (CCI = 0), moderate (CCI = 1-2), and severe (CCI≥3) comorbidity were 23.6%, 65.9%, and 10.5%, respectively. During a median follow-up of 2.9 (1.5, 3.6) years, compared with patients without OSA, the presence of OSA increased the risk of MACCE in the moderate comorbidity group (22.6% vs. 17.5%; adjusted HR: 1.327; 95% CI: 1.019-1.728, p = 0.036) and severe comorbidity group (36.2% vs. 18.6%; adjusted HR: 2.194; 95% CI: 1.170-4.117, p = 0.014). There was no significant difference between OSA and non-OSA patients in the mild comorbidity group. CONCLUSION: Among ACS patients, OSA was associated with an increased risk of subsequent events in the moderate and severe comorbidity groups but not in the mild comorbidity group. ACS patients with comorbidities should not be overlooked for OSA screening.

Effect of obstructive sleep apnea on prognosis in patients with acute coronary syndromes with varying numbers of standard modifiable risk factors: insight from the OSA-ACS study.

BACKGROUND: Standard 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. METHODS: This 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. RESULTS: Among 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. CONCLUSIONS: In 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.

Effect of obstructive sleep apnoea on coronary collateral vessel development in patients with ST-segment elevation myocardial infarction.

BACKGROUND AND OBJECTIVE: The impact of obstructive sleep apnoea (OSA) in the setting of acute ST-segment elevation myocardial infarction (STEMI) is complex and divergent. This study aimed to investigate the association between OSA and coronary collateral vessel (CCV) development in patients with STEMI. METHODS: The present study prospectively screened 282 STEMI patients with an overnight sleep study. OSA was defined as apnoea-hypopnoea index (AHI) ≥15 events/h. The coronary angiograms were used for the assessment of Rentrop grades representing CCVs. RESULTS: Among 119 patients enrolled, 60 patients had OSA (50.4%). The prevalence of CCV development (Rentrop grade ≥ 2) was significantly higher in OSA group than in the non-OSA group (43.3% vs. 5.1%, p < 0.001). There was a parallel increase in the Rentrop grades associated with OSA severity and worsening of hypoxaemia indicators (minimum arterial oxygen saturation [SaO2 ], mean SaO2 and time with SaO2 below 90%). After adjustment for clinical and angiographic characteristics, and pre-procedure medications that might interact with OSA, AHI as a continuous variable (OR 1.11, 95% CI 1.08-1.21, p < 0.001) and the presence of OSA (OR 11.41, 95% CI 2.70-48.15, p = 0.001) were both associated with dramatically higher incidence of CCV development. CONCLUSION: Our study demonstrated that the presence of OSA might augment CCV development in STEMI patients. The potential protective effects and mechanisms of OSA in the acute setting of STEMI should be further investigated in larger studies.

The value of nurse-led anthropometric and oropharyngeal measurements combined with STOP-Bang questionnaire in screening for obstructive sleep apnea in patients with acute coronary syndrome: a prospective cohort study.

BACKGROUND: Obstructive sleep apnea (OSA) is a modifiable risk factor for acute coronary syndrome (ACS), with high prevalence but low diagnostic rates. Therefore, it is particularly important to develop strategies for better screening for OSA in newly admitted ACS patients. METHODS: From March 2017 to October 2019, consecutive eligible patients with ACS underwent cardiorespiratory polygraphy during hospitalization. OSA was defined as an apnea-hypopnea index (AHI) ≥ 15 events/h. All anthropometric and oropharyngeal parameters are measured by specialist nurses. RESULTS: Finally, 761 ACS patients were recruited in the present study. Prevalence of moderate/severe OSA was 53.2% based on diagnostic criteria of AHI ≥ 15. Correlation analysis illustrated that AHI was positively correlated with anthropometric characteristics. In the multivariate model, only micrognathia (OR 2.02, 95% CI 1.02-4.00, P = 0.044), waist circumference (OR 1.08, 95% CI 1.04-1.11, P < 0.001), and STOP-BANG Questionnaire (SBQ) score (OR 1.45, 95% CI 1.27-1.66, P < 0.001) were independently associated with the prevalence of OSA. Receiver operating characteristic curve (ROC) analysis showed that the area under curve (AUC) of multivariable joint diagnosis (waist circumference, micrognathia combined with SBQ) was significantly better than the AUC of Epworth Sleepiness Scale (ESS) and SBQ (p < 0.0001 and p = 0.0002, respectively), and the results showed that AUC was 0.728. Under the optimal truncation value, the sensitivity was 73%, and the specificity was 61%, which was higher than the single index. Finally, we also constructed a nomogram model based on multiple logistic regression, to easily determine the probability of OSA in ACS patients. CONCLUSIONS: The new screening tool has greater power than single questionnaire or measurements in screening of OSA among ACS patients. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT03362385, registered December 5, 2017.

Association of C1q/TNF-Related Protein-9 (CTRP9) Level with Obstructive Sleep Apnea in Patients with Coronary Artery Disease.

BACKGROUND: Obstructive sleep apnea (OSA) is closely related to the incidence and progression of coronary artery disease (CAD), and the mechanisms linking OSA and CAD are multifactorial. C1q/TNF-related protein-9 (CTRP9) is a novel adipokine that protects the heart against ischemic injury and ameliorates cardiac remodeling. We aimed to ascertain the clinical relevance of CTRP9 with OSA prevalence in patients with CAD. METHODS: From August 2016 to March 2019, consecutive eligible patients with CAD (n = 154; angina pectoris, n = 88; acute myocardial infarction [AMI], n = 66) underwent cardiorespiratory polygraphy. OSA was defined as an apnea-hypopnea index (AHI) ≥15 events·h-1. Plasma CTRP9 concentrations were measured by ELISA method. RESULTS: Moderate/severe OSA was present in 89 patients (57.8%). CTRP9 levels were significantly decreased in the moderate/severe OSA group than in the no/mild OSA group (4.7 [4.1-5.2] ng/mL vs. 4.9 [4.4-6.0] ng/mL, P = 0.003). The difference between groups was only observed in patients with AMI (3.0 [2.3-4.9] vs. 4.5 [3.2-7.9], P = 0.009). Correlation analysis showed that CTRP9 levels were negatively correlated with AHI (r = -0.238, P = 0.003) and oxygen desaturation index (r = -0.234, P = 0.004) and positively correlated with left ventricular ejection fraction (r = 0.251, P = 0.004) in all subjects. Multivariate analysis showed that male gender (OR 3.099, 95% CI 1.029-9.330, P = 0.044), BMI (OR 1.148, 95% CI 1.040-1.268, P = 0.006), and CTRP9 levels (OR 0.726, 95% CI 0.592-0.890, P = 0.002) were independently associated with the prevalence of moderate/severe OSA. CONCLUSIONS: Plasma CTRP9 levels were independently related to the prevalence of moderate/severe OSA in patients with CAD, suggesting that CTRP9 might play a role in the pathogenesis of CAD exacerbated by OSA.

Prognostic impact of residual SYNTAX score in patients with obstructive sleep apnea and acute coronary syndrome: a prospective cohort study.

BACKGROUND: There is a paucity of data from large prospective study evaluating the prognostic significance of the residual Synergy between percutaneous intervention with Taxus drug-eluting stents and cardiac surgery (SYNTAX) Score (rSS) in patients with obstructive sleep apnea (OSA) and Acute Coronary Syndrome (ACS). METHODS: ACS patients who undergoing percutaneous coronary angiography and completing a sleep study during hospitalization were prospectively enrolled. The baseline SYNTAX Score (bSS) and the rSS after revascularization were assessed. Complete revascularization (CR, rSS = 0) and incomplete revascularization (ICR, rSS > 0) were categorized. OSA (apnea hypopnea index, AHI ≥ 15) and non-OSA (AHI < 15) were grouped according to AHI. The primary endpoint of the study was major adverse cardiovascular and cerebrovascular events (MACCEs), defined as a composite of cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization, or hospitalization for UAP or heart failure. RESULTS: Overall, 752 patients were prospectively enrolled. At a median follow-up of 1 year, the incidence of MACCEs was significantly higher in the OSA than in the non-OSA group (hazard ratio [HR]:1.68; 95% confidence interval [CI]:1.04-2.72; P = .034). ICR was associated with a higher risk of MACCEs in the non-OSA group (HR:3.34;95% CI:1.0-11.12; P = .05). The OSA patients with ICR had a 5.1 higher risk of MACCEs compared with the non-OSA with CR group, P = .007. The OSA patients with CR had a similar 1-year MACCEs as all the non-OSA patients (HR:1.10; 95% CI:0.515-2.349; P = 0.806). CONCLUSIONS: ACS patients with OSA and ICR have a high rate of MACCEs at 1 year. In contrast, the prognosis of ACS patients with OSA but CR is favorable and similar to patients without OSA. Adequate level of revascularization is recommended to optimize clinical outcomes in ACS patients with OSA. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT03362385.

Effect of continuous positive airway pressure on long-term cardiovascular outcomes in patients with coronary artery disease and obstructive sleep apnea: a systematic review and meta-analysis.

BACKGROUND: Obstructive sleep apnea (OSA) is highly prevalent in patients with coronary artery disease (CAD) and is associated with recurrent cardiovascular risk. However, whether treatment with continuous positive airway pressure (CPAP) reduces this risk remains unclear. We performed a systematic review and meta-analysis to assess the effect of CPAP on long-term cardiovascular outcomes in patients with concomitant CAD and OSA. METHODS: We searched the PubMed, EMBASE, and Cochrane library from their inceptions to October 7, 2017. We included observational studies and randomized controlled trials (RCTs) that described the association of CPAP treatment with cardiovascular events in patients with CAD and OSA. The primary outcome of interest was major adverse cardiovascular event (MACE), including all-cause or cardiovascular death, myocardial infarction, stroke, repeat revascularization, or hospitalization for heart failure. Outcomes data were pooled using random effects models and heterogeneity assessed with the I2 statistic. RESULTS: We identified 9 studies (2 RCTs and 7 observational studies) with 1430 participants. The median follow-up duration was from 36 to 86.5 months. Treatment with CPAP was associated with a significantly lower risk of MACE in 6 observational studies (RR 0.61, 95% CI: 0.39-0.94, P = 0.02), but this was not reproduced in 2 RCTs (RR 0.57, 95% CI: 0.32-1.02, P = 0.06). Similarly, CPAP significantly reduced the risk of all-cause death (4 observational studies) and cardiovascular death (3 observational studies), which were also not confirmed in RCTs. CONCLUSIONS: The use of CPAP in patients with CAD and OSA might prevent subsequent cardiovascular events, which was only demonstrated in observational studies, but not in RCTs. The value of CPAP therapy as second prevention for CAD needs further investigation.

Endothelial Cell-Derived Microparticles from Patients with Obstructive Sleep Apnea Hypoxia Syndrome and Coronary Artery Disease Increase Aortic Endothelial Cell Dysfunction.

BACKGROUND/AIMS: Obstructive sleep apnea hypoxia syndrome (OSAHS) is an independent risk factor for coronary artery disease (CAD). Treatment of OSAHS improves clinical outcome in some CAD patients, but the relationship between OSAHS and CAD is complex. Microparticles (MPs) are shed by the plasma membrane by either physiologic or pathologic stimulation. In the current study, we investigated the role of MPs in the context of OSAHS. METHODS AND RESULTS: 54 patients with both suspected coronary artery stenosis and OSAHS were recruited and underwent both coronary arteriography and polysomnography. Circulating MPs were isolated and analyzed by flow cytometry. CAD+OSAHS patients exhibited greater levels of total MPs (Annexin V+), erythrocyte-derived MPs (CD235+ Annexin V+), platelet-derived MPs (CD41+ Annexin V+), and leukocyte-derived MPs (CD45+ Annexin V+) compared to CAD alone patients or control. CAD+OSAHS patients expressed the greatest level of endothelial-derived MPs of all cellular origin types (CD144+ Annexin V +). Treatment of human aortic endothelial cells (HAECs) with MPs isolated from CAD+OSAHS patients markedly increased HAEC permeability (as detected by FITC-dextran), and significantly upregulated mRNA levels of ICAM-1, VCAM-1, and MCP-1. CONCLUSION: OSAHS+CAD patients harbor increased levels of MPs, particularly the endothelial cell-derived subtype. When administered to HAECs, OSAHS+CAD patients MPs increase endothelial cell permeability and dysfunction.

The effect of miR-223-3p on endothelial cells in coronary artery disease.

Endothelial cell damage and dysfunction are crucial factors in the development and early stages of coronary artery disease (CAD) and apoptosis plays a significant role in this process. In this study, We aimed to simulate the CAD vascular microenvironment by treating endothelial cells with tumor necrosis factor alpha (TNF-α) to construct an endothelial cell apoptosis model. Our findings revealed that the TNF-α model resulted in increased micro-RNA 223-3p (miR-223-3p) mRNA and Bax protein expression, decreased kruppel-like factor 15 (KLF15) and Bcl-2 protein expression, and decreased cell viability. More importantly, in the TNF-α-induced endothelial cell apoptosis model, transfection with the miR-223-3p inhibitor reversed the effects of TNF-α on Bcl-2, Bax expression. We transfected miRNA-223-3p mimics or inhibitors into endothelial cells and assessed miR-223-3p levels using RT-PCR. Cell viability was detected using CCK8. Western blot technology was used to detect the expression of Bcl-2, Bax, and KLF15. In summary, this study demonstrates the role and possible mechanism of miR-223-3p in endothelial cells during CAD, suggesting that miR-223-3p may serve as a promising therapeutic target in CAD by regulating KLF15.

Impact of obstructive sleep apnea on prognosis of patients with cardiometabolic multimorbidity.

BACKGROUND: Cardiometabolic multimorbidity (CMM) is a growing global health problem, and obstructive sleep apnea (OSA) is recognized as an important risk factor for cardiovascular disease. However, the impact of OSA on the prognosis of CMM patients remains unclear. METHODS: This study was a sub-study of OSA-acute coronary syndrome (ACS) and included 1, 927 hospitalized ACS patients. Patients were divided into the CMM group and the non-CMM group. OSA was diagnosed using the apnea-hypopnea index (AHI). The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). The secondary endpoint included cardiac events, all-cause death and all repeat revascularizations. RESULTS: This study enrolled 1, 927 patients hospitalized for ACS, with a median follow-up of 3 years. Among them, 723 patients (37.5%) had CMM, while 1, 204 patients (62.5%) did not have CMM. Over half of the patients in each group had OSA. OSA patients exhibited worse cardiometabolic profiles than their non-OSA counterparts, including higher body mass index (BMI), glycemic indices, lipids and inflammation. In the CMM group, OSA patients had a significantly higher incidence of MACCE than non-OSA patients (34.7% vs. 23.7%, p = 0.004). These results remained significant after adjustment, indicating that OSA substantially increased the risk of MACCE in the CMM group (adjusted hazard ratio [HR]: 1.432; 95% confidence interval [CI]: 1.017-2.016; p = 0.040). Conversely, the incidence of MACCE was similar between OSA and non-OSA subgroups within the non-CMM cohort. Subgroup analyses showed that OSA increased the risk of MACCE in CMM patients aged ≥ 60 years (adjusted HR: 1.642; 95% CI: 1.031-2.615; p = 0.037) and in those with specific clinical characteristics. CONCLUSION: OSA significantly impacts the prognosis of CMM patients, highlighting the need for targeted OSA screening and management strategies to improve outcomes in this population potentially.

Prognostic effect of obstructive sleep apnea in acute coronary syndrome patients with heart failure.

BACKGROUND AND OBJECTIVE: Acute coronary syndrome (ACS), heart failure (HF) and obstructive sleep apnea (OSA) often overlap and interact, the impact of OSA on ACS patients with HF remains unclear. The study sought to comprehensively evaluate the effects of the interaction between OSA and HF on long-term cardiovascular outcomes in ACS patients. METHODS: Between June 2015 and January 2020, patients hospitalized for ACS were prospectively enrolled and underwent portable sleep monitoring after clinically stabilization. OSA was defined as an apnea hypopnea index ≥15 events/h. HF was defined using medical records. The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE), including death, myocardial infarction, stroke, ischemia-driven revascularization, and hospitalization for unstable angina. RESULTS: Among all 1927 included patients, 214 (11.1 %) had HF, and 1014 (52.6 %) had OSA. For 2.9 years (1.5, 3.6 years) follow-up, OSA was independently associated with the risk of MACCE in HF patients (adjusted hazard ratio [HR], 2.11; 95%CI, 1.16-3.84; P = 0.014), but not in those without HF (adjusted HR, 1.15; 95%CI, 0.92-1.45; P = 0.228). Further analysis showed OSA exerted more prognostic effect in HF patients with preserved eject fraction (adjusted HR, 2.45; 95 % CI, 1.11-5.41; P = 0.027) than those with reduced eject fraction (adjusted HR, 1.62; 95 % CI, 0.63-4.20; P = 0.319). CONCLUSIONS: In the settings of ACS, OSA was independently associated with poor prognosis in patients with concomitant HF especially those with persevered ejection fraction. Screening and treatment for OSA are highly recommended in ACS patients with HF. CLINICAL TRIAL REGISTRATION: URL: www.clinicaltrails.gov; Unique Identifier: NCT03362385.

The long-term prognostic implications of free triiodothyronine to free thyroxine ratio in patients with obstructive sleep apnea and acute coronary syndrome.

Objective: Obstructive sleep apnea (OSA) and thyroid dysfunction frequently overlap clinically and are risk factors for cardiovascular disease. The free triiodothyronine to free thyroxine (FT3/FT4) ratio as a novel biomarker of cardiovascular disease prognosis, but the impact of the FT3/FT4 ratio on the prognosis of OSA in patients with acute coronary syndromes (ACS) remains uncertain. Methods: In this prospective cohort study, 2160 patients with ACS were recruited and underwent portable sleep monitoring at Beijing Anzhen Hospital from June 2015 to January 2020. OSA was diagnosed when apnea-hypopnea index of ≥15 events/h. Patients were further divided into tertiles according to FT3/FT4 ratio. All patients had scheduled follow-up visits at 1, 3, 6, 9 and 12 months after discharge, with subsequent outpatient visits or telephone follow-up visits every 6 months. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including cardiovascular death, myocardial infarction (MI), stroke, ischemia-driven revascularization, or hospitalization for unstable angina or heart failure. Results: Among 1,547 euthyroid patients enrolled (mean age, 56.0 ± 10.5 years), 812 patients (52.5%) had OSA. The FT3/FT4 ratio between OSA and non-OSA patients was not significantly different. During 2.8 (1.4, 3.5) years follow up, the risk of MACCE increased with the decreasing FT3/FT4 tertiles in patients with OSA (tertile3 as reference, tertile2: hazard ratio (HR) 1.26, 95% CI: 0.85-1.86, P = 0.255; tertile1: 1.60, 95% CI 1.11-2.32; P = 0.013). After adjustment for confounders, the lowest FT3/FT4 tertile was still independently associated with an increased risk of MACCE (adjusted HR 1.66, 95% CI 1.11-2.50, P = 0.015). Conclusion: Lower FT3/FT4 ratio associated with poor prognosis in patients with ACS and OSA.

The Long-Term Prognostic Role of Nighttime Resting Heart Rate in Obstructive Sleep Apnea in Patients with Acute Coronary Syndrome.

AIM: A close relationship exists between resting heart rate (RHR) and obstructive sleep apnea (OSA). Still, the prognostic importance of nighttime RHR in patients with acute coronary syndrome (ACS) with or without OSA remains unclear. METHODS: In this prospective cohort study, OSA was defined as an apnea-hypopnea index of ≥ 15 events/h, and the high nighttime RHR (HNRHR) was defined as a heart rate of ≥ 70 bpm. The primary endpoint was a major adverse cardiovascular and cerebrovascular event (MACCE), including cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization, or hospitalization for heart failure. RESULTS: Among the 1875 enrolled patients, the mean patient age was 56.3±10.5 years, 978 (52.2%) had OSA, and 425 (22.7%) were in HNRHR. The proportion of patients with HNRHR is higher in the OSA population than in the non-OSA population (26.5% vs. 18.5%; P＜0.001). During 2.9 (1.5, 3.5) years of follow-up, HNRHR was associated with an increased risk of MACCE in patients with OSA (adjusted HR: 1.56, 95% CI: 1.09-2.23, P=0.014), but not in patients without OSA (adjust HR: 1.13, 95% CI: 0.69-1.84, P=0.63). CONCLUSIONS: In patients with ACS, a nighttime RHR of ≥ 70 bpm was associated with a higher risk of MACCE in those with OSA but not in those without it. This identifies a potential high-risk subgroup where heart rate may interact with the prognosis of OSA. Further research is needed to determine causative relationships and confirm whether heart rate control impacts cardiovascular outcomes in patients with ACS-OSA.

The role of ferroptosis-related genes in airway epithelial cells of asthmatic patients based on bioinformatics.

It has been reported that airway epithelial cells and ferroptosis have certain effect on asthma. However, the action mechanism of ferroptosis-related genes in airway epithelial cells of asthmatic patients is still unclear. Firstly, the study downloaded the GSE43696 training set, GSE63142 validation set and GSE164119 (miRNA) dataset from the gene expression omnibus database. 342 ferroptosis-related genes were downloaded from the ferroptosis database. Moreover, differentially expressed genes (DEGs) between asthma and control samples in the GSE43696 dataset were screened by differential analysis. Consensus clustering analysis was performed on asthma patients to classify clusters, and differential analysis was performed on clusters to obtain inter-cluster DEGs. Asthma-related module was screened by weighted gene co-expression network analysis. Then, DEGs between asthma and control samples, inter-cluster DEGs and asthma-related module were subjected to venn analysis for obtaining candidate genes. The last absolute shrinkage and selection operator and support vector machines were respectively applied to the candidate genes to screen for feature genes, and functional enrichment analysis was performed. Finally, a competition endogenetic RNA network was constructed and drug sensitivity analysis was conducted. There were 438 DEGs (183 up-regulated and 255 down-regulated) between asthma and control samples. 359 inter-cluster DEGs (158 up-regulated and 201 down-regulated) were obtained by screening. Then, the black module was significantly and strongly correlated with asthma. The venn analysis yielded 88 candidate genes. 9 feature genes (NAV3, ITGA10, SYT4, NOX1, SNTG2, RNF182, UPK1B, POSTN, SHISA2) were screened and they were involved in proteasome, dopaminergic synapse etc. Besides, 4 mRNAs, 5 miRNAs, and 2 lncRNAs collectively formed competition endogenetic RNA regulatory network, which included RNF182-hsa-miR-455-3p-LINC00319 and so on. The predicted therapeutic drug network map contained NAV3-bisphenol A and other relationship pairs. The study investigated the potential molecular mechanisms of NAV3, ITGA10, SYT4, NOX1, SNTG2, RNF182, UPK1B, POSTN, SHISA2 in airway epithelial cells of asthmatic patients through bioinformatics analysis, providing a reference for the research of asthma and ferroptosis.

Obstructive sleep apnea is associated with the long-term prognosis of patients in acute coronary syndromes with prior myocardial infarction: Insights from OSA-ACS study.

OBJECTIVE: The prognostic significance of obstructive sleep apnea (OSA) in patients with acute coronary syndrome (ACS) according to prior myocardial infarction (MI) remains unclear. We aimed to investigate the association between OSA and long-term cardiovascular outcomes in ACS patients with or without prior MI. METHODS: We prospectively recruited eligible 2160 ACS patients with portable sleep monitoring in Beijing Anzhen Hospital between June 2015 and January 2020. OSA was defined as an apnea hypopnea index (AHI) ≥15 events/hour. The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE), including cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization, or hospitalization for unstable angina or heart failure. RESULTS: Among 1927 patients enrolled, 1014 (52.6%) had OSA and 316 (16.4%) had prior MI. During 2.9 (1.5, 3.6) years of follow-up, multivariate analysis showed that OSA was associated with 1.7 times the risk of MACCE in patients with prior MI (50 events [28.2%] vs 24 events [17.3%]; adjusted HR = 1.74, 95%CI 1.04-2.90, P = 0.034), but not in patients without prior MI group (177 events [21.1%] vs 138 events [17.8%]; adjusted HR = 1.19, 95%CI 0.94-1.51, P = 0.15). There was no significant interaction between prior MI and OSA for MACCE (interaction P = 0.14). CONCLUSIONS: OSA was independently associated with an increased risk of MACCE among ACS patients, particularly among ACS patients with prior MI. Further trials exploring the efficacy of OSA treatment in high-risk patients with ACS characterized by prior MI are warranted.