Skip to main content

Clinical significance of obstructive sleep apnea in patients with acute coronary syndrome with or without prior stroke: a prospective cohort study

Abstract

Background and objective

Whether obstructive sleep apnea (OSA) is associated with worse prognosis in patients with acute coronary syndrome (ACS) with or without prior stroke remains unclear. We investigated the association of OSA with cardiovascular events in ACS patients with or without prior stroke.

Methods

Between June 2015 and January 2020, we prospectively recruited eligible ACS patients who underwent cardiorespiratory polygraphy during hospitalization. We defined OSA as an apnea hypopnea index (AHI) ≥ 15 events/hour. The primary composite end point was major adverse cardiovascular and cerebrovascular events (MACCEs), including cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization, or hospitalization for unstable angina or heart failure.

Results

Among 1927 patients enrolled, 207 patients had prior stroke (10.7%) and 1014 had OSA (52.6%). After a mean follow-up of 2.9 years, patients with stroke had significantly higher risk of MACCEs than those without stroke (hazard ratio [HR]:1.49; 95% confidence interval [CI]: 1.12–1.98, P = 0.007). The multivariate analysis showed that patients with OSA had 2.0 times the risk of MACCEs in prior stroke group (41 events [33.9%] vs 18 events [20.9%]; HR:2.04, 95% CI:1.13–3.69, P = 0.018), but not in non-prior stroke group (186 events [20.8%] vs 144 events [17.4]; HR:1.21, 95% CI 0.96–1.52, P = 0.10). No significant interaction was noted between prior stroke and OSA for MACCE (interaction P = 0.17).

Conclusions

Among ACS patients, the presence of OSA was associated with an increased risk of cardiovascular events in patients with prior stroke. Further trials exploring the efficacy of OSA treatment in high-risk patients with ACS and prior stroke are warranted.

Trial registration Clinicaltrials.gov identifier NCT03362385.

Background

Obstructive sleep apnea (OSA) is a complex and heterogeneous common chronic disease characterized by repetitive episodes of upper airway collapse, affecting 40%–60% of patients with ACS [1, 2]. Current evidence has shown that OSA initiates and exacerbates coronary atherosclerosis and is closely related to poor outcomes in patients with ACS or cerebrovascular disease [1, 3,4,5,6]. However, several randomized controlled trials have indicated that treatment with continuous positive airway pressure (CPAP) is not associated with lower rates of recurrent cardiovascular events in patients with ACS [7,8,9,10]. It is well known that ACS and stroke share common pathogeneses, such as lipid disorders and arterial thrombosis. For that reason, ACS patients presenting with a history of stroke were not uncommon, constituted 8.25% of patients, and presented a therapeutic conundrum [11]. Furthermore, patients with prior stroke had particularly poor outcomes compared with those without prior stroke, including a higher risk of death, MI, and stroke [11,12,13,14,15]. Preliminary evidence also suggests that OSA is an independent risk factor for stroke and is associated with recurrent ischemic stroke and worsening outcomes [16,17,18]. Although whether CPAP treatment reduces the risk of stroke in OSA patients remains controversial, patients’ adherent to CPAP therapy (> 4 h per day) may benefit [19]. In addition, it is unclear whether the effect of OSA on the prognosis of patients with ACS varies based on previous stroke. Considering the association between ACS, OSA and stroke, we hypothesized that OSA combined with prior stroke may have a synergistic deleterious effect that increases future cardiovascular risk. Hence, based on a large, prospective cohort study, we evaluated the impact of OSA on the risk of cardiovascular events in ACS patients with or without prior stroke.

Methods

Study design and population

The OSA-ACS project (NCT03362385) is a prospective, observational, single-center study designed to evaluate the association between OSA and cardiovascular outcomes among patients with ACS. The study design has been described previously [3, 20]. In the current study, we aimed to investigate the clinical importance of OSA for patients with ACS stratified by stroke history. In brief, from June 2015 to January 2020, in the Center for Coronary Artery Disease at Beijing Anzhen Hospital, Capital Medical University, ACS patients aged 18 years to 85 years were enrolled and underwent overnight sleep studies. The exclusion criteria included cardiac arrest or cardiogenic shock, malignancies, and failed sleep studies (those who failed to obtain adequate and satisfactory recordings). Next, patients with predominantly central sleep apnea (≥ 50% central events and a central apnea–hypopnea index (AHI) ≥ 10/h), recording time < 180 min, and those receiving regular CPAP therapy (> 4 h/day and > 21 days/month) after discharge were excluded. The protocol was approved by the Ethics Committee of Beijing Anzhen Hospital, Capital Medical University (2,013,025). All participants provided written informed consent, and the study was conducted according to the amended Declaration of Helsinki. Thirty patients were lost to follow-up and therefore excluded from the analysis. The study flowchart is presented in Fig. 1.

Fig. 1
figure 1

Flowchart of the study. ACS, acute coronary syndrome; CPAP, continuous positive airway pressure; OSA, obstructive sleep apnea

Overnight sleep study

For eligible patients with a hospital stay of 24–72 h, an overnight sleep study was conducted using portable cardiorespiratory polygraphy (ApneaLink Air, ResMed, Australia), which has previously been validated [21, 22]. All sleep studies were double scored manually by independent sleep somnologists blinded to the clinical characteristics, and confirmed by a senior somnologist in cases of discrepancy. They reviewed all the data and checked whether there are missed or misjudged events. The following signals were recorded: nasal airflow, thoraco-abdominal movements, snoring episodes, pulse, and percutaneous oxygen saturation (SpO2). Apnea was defined as an absence of airflow for 10 s or more. Hypopnea was defined as an airflow reduction of 30% for ≥ 10 s with a decrease in SpO2 > 4%. Oxygen desaturation was defined as a decrease in arterial oxygen saturation greater than 4%. The AHI was defined as the number of episodes of apnea hypopnea per hour of recording. The oxygen desaturation index (ODI) was calculated as the amount of time when the oxygen saturation dropped by ≥ 4% from baseline per hour of sleep. Valid tests required a minimum of 3 h of satisfactory signal recording. In accordance with previous studies, recruited patients were categorized into OSA (AHI ≥ 15 events/h) and non-OSA (AHI < 15 events/h) groups [4, 23].

Procedures and management

Clinical care for all patients was offered at the discretion of the attending clinician based on current guidelines [24, 25]. When clinically indicated, PCI with stenting or coronary artery bypass graft (CABG) was performed. Patients with OSA, particularly those with excessive daytime sleepiness, were referred to sleep centers for further evaluation and treatment.

Follow-up and outcomes

Following the sleep study, follow-ups were performed at one month, three months, and six months and then every six months afterwards. Clinical visits, medical chart reviews, and telephone calls by two investigators blinded to the patients' clinical information were used to collect clinical event data. At each visit, a composite of cardiovascular events was assessed, and events were then confirmed by source documentation and adjudicated by the clinical event committee.

Major adverse cardiovascular and cerebrovascular events (MACCEs), defined as a composite of cardiovascular death, MI, stroke, ischemia-driven revascularization, or hospitalization for unstable angina or heart failure, were the primary outcomes of this study. Secondary cardiovascular endpoints included the individual components of the primary composite endpoint and other composites of cardiovascular events, including cardiovascular death, MI, or stroke. The endpoints were defined according to the Standards for Data Collection in Cardiovascular Trials Initiative [26].

Statistical analysis

Data were compared using Student's t test or the Mann–Whitney U test for continuous variables expressed as means ± standard deviations or medians (interquartile ranges). Counts and proportions (%) for categorical variables were compared using Fisher’s exact test or χ2 statistics as appropriate. The Kaplan–Meier product limit method was used to calculate the survival rate as the period from the initial sleep study to any MACCEs, with the data censored at the last recorded follow-up. Cox regression analysis was used to investigate independent risk factors for endpoints, and adjusted hazard ratios (HR) with 95% CI were calculated. Cox regression models were built using baseline variables that were considered clinically relevant or demonstrated a univariate relationship with the outcomes. The AHI was divided by AHI < 15, 15–30, > 30 to assess the relationship between OSA severity and the risk of cardiovascular events in patients with or without prior stroke. Multiplicative interaction terms were included in the fully adjusted models to evaluate if prior stroke modified the associations between OSA and risk of cardiovascular events. All analyses were conducted with SPSS V.26.0 (IBM SPSS, Armonk, New York, USA). A two-sided P < 0.05 was considered statistically significant.

Results

Baseline characteristics

Between June 2015 and January 2020, a total of 2160 patients with ACS were recruited, of whom 2109 underwent successful cardio-respiratory polygraphy. Among them, 1,969 patients with OSA and follow-up were included. Among them, only 42 (2.1%) of patients received regular CPAP therapy (> 4 h/day and > 21 days/month) and the rate was similar between those with and without prior stroke (2.8% vs. 2.1%, P = 0.47). A total of 1927 ACS patients met the initial eligibility criteria and 207 patients (10.74%) had a stroke history. A previous stroke was associated with older age, a less proportion of males, higher systolic blood pressure, and a higher prevalence of established risk factors, such as diabetes, hypertension, and hyperlipidemia, a lower level of Min SpO2, Mean SpO2, and a higher level of T90 SpO2 < 90%. Previous MI, PCI, and CABG rates were similar between the two groups (Additional file 1: Table S1).

The baseline characteristics of the OSA and non-OSA groups with or without prior stroke are shown in Table 1. Patients with OSA exhibited a higher body mass index (BMI) and neck and waist circumferences, irrespective of prior stroke. In the non-prior stroke group, patients with OSA were more males, more likely to have hypertension and prior PCI, had higher level of glycosylated hemoglobin and C-reactive protein, lower level of high-density lipoprotein, and lower left ventricular ejection fraction, and more likely to receive PCI and CABG procedures. In both the prior stroke group and the non-prior stroke group, other characteristics were generally well matched between OSA and non-OSA patients.

Table 1 Characteristics of the patients at baseline

Results of the sleep study

The characteristics differed significantly between the two groups. The prevalence of OSA was 52.6%, and patients with OSA had a lower minimum oxygen saturation than those without OSA. Further information is shown in Table 2.

Table 2 Results of sleep study

Outcomes in the overall population according to OSA and prior stroke

The mean median follow-up time was 2.9 years (1.5 to 3.6). Among patients with ACS, the presence of OSA was associated with a higher rate of MACCE compared with patients without OSA in the overall population (log-rank, P = 0.004). Kaplan–Meier analysis showed that the cumulative incidence of MACCEs was significantly higher in the prior stroke group than in the non-prior stroke group (log-rank, P < 0.001; Additional file 1: Fig. S1). After adjustment for the baseline risk of cardiovascular events, patients with prior stroke were strongly associated with a higher rate of MACCEs than patients without prior stroke (HR: 1.49, 95% CI: 1.12–1.98, P = 0.007). Furthermore, the patients were classified into three different groups based on their AHI: no/mild OSA (AHI < 15), moderate OSA (15 ≤ AHI ≤ 30), and severe OSA (30 < AHI). The association between OSA and MACCE among patients with prior stroke remained significant in moderate and severe OSA compared with the no/mild OSA (Additional file 1: Fig. S2).

Outcomes of OSA versus non-OSA patients stratified by prior stroke

In the prior stroke group, Kaplan–Meier analysis showed that MACCEs were significantly more common in the OSA group than in the non-OSA group (log-rank, P = 0.019; Fig. 2A). In the non-prior stroke group, the incidence of MACCEs was also higher in the OSA group than in the non-OSA group (log-rank, P = 0.039; Fig. 2B). After adjustment for age, sex, body mass index, smoking status, hypertension, diabetes mellitus and dyslipidemia, OSA was associated with an increased risk of MACCEs in the prior stroke group (HR: 2.04, 95% CI: 1.13–3.69, P = 0.018) but not in the non-prior stroke group (HR: 1.21, 95% CI: 0.96–1.52, P = 0.10) (Table 3). No significant interaction was noted between prior stroke and OSA for MACCE (interaction P = 0.17).

Fig. 2
figure 2

Kaplan–Meier curves for the analysis cardiovascular events in OSA versus non-OSA groups in prior stroke group and non-prior stroke group. Kaplan–Meier estimates hospitalization for MACCE (A, B) and composite of cardiovascular death, myocardial infarction, and stroke (C, D) between OSA and non-OSA groups in prior stroke group (A, C) and non-prior stroke group (B, D). MACCE, major adverse cardiovascular and cerebrovascular event. OSA, obstructive sleep apnea

Table 3 Cox regression analyses evaluating the association between OSA and risk of cardiovascular events by a history of stroke

Among patients with prior stroke, Kaplan–Meier analysis showed that the cumulative incidence of composite events of cardiovascular death, MI, or stroke was significantly higher in the OSA group than in the non-OSA group (log-rank, P = 0.015; Fig. 2C) but not among patients with non-prior stroke (log-rank, P = 0.23; Fig. 2D). The fully adjusted multivariable Cox regression model analysis showed that the association between OSA and the outcomes remained statistically significant in the prior stroke group (HR: 2.84, 95% CI: 1.17–6.93, P = 0.022) but not in the non-prior stroke group (HR: 1.19, 95% CI: 0.78–1.84, P = 0.44). The other endpoints were not different and are listed in Table 3. The crude numbers of events are listed in Additional file 1: Table S2. We also performed additional subgroup analyses according to prior coronary artery disease, prior myocardial infarction, and prior cardiovascular diseases (myocardial infarction, history of revascularization, heart failure, or atrial fibrillation/flutter). Although differences were found between some subgroups, the association of OSA with MACCE was not modified by these confounding factors (interaction P > 0.14 for all) (Additional file 1: Table S3). Then, we calculated the MACCE rate between CPAP and non-CPAP groups in prior stroke (33.3% vs 33.9%, P = 0.99) and non-prior stroke groups (19.4% vs 20.8%, P = 0.99) and found no significant differences in both groups.

Discussion

To our knowledge, this is the first prospective study evaluating the prognostic value of OSA in ACS patients with or without prior stroke. After adjustment for potential confounders, compared with patients without OSA, patients with OSA had a 2.0-fold higher risk of MACCE in the prior stroke group, but not in the non-prior stroke group, although no significant interaction was noted between prior stroke and OSA for MACCE (interaction P = 0.17). The incidence of composite events of cardiovascular death, MI, or stroke was also significantly higher in the OSA versus non-OSA group among patients with prior stroke but not among those without prior stroke.

Given that ACS and stroke have similar pathogeneses, such as atherosclerosis and thrombosis, it is not surprising that prior stroke plays an important role in determining ACS outcome [14, 27]. Studies have indicated that the percentage of patients with ACS and a prior stroke is approximately 10% [28]. Our findings are consistent with recent data showing that 10.74% of patients had a history of prior stroke, and previous stroke patients tended to be older, were more likely to be female, and were more likely to have diabetes, hypertension, and hyperlipidemia. Recently, a large study revealed that patients with prior stroke who undergo PCI have an increased risk of long-term cardiovascular and cerebrovascular complications, specifically recurrent strokes [13]. Similarly, we also found that prior stroke significantly predicted subsequent cardiovascular events in ACS patients. Atherosclerosis, comorbidities, cardiovascular risk factors, and low use of medical and invasive therapy might contribute to poor outcomes in patients with a history of stroke [15, 29]. Therefore, given the high incidence of prior stroke among ACS patients and its possible effect on prognosis, greater attention should be given to ACS patients with prior stroke.

Current evidence indicates that OSA is closely related to poor outcomes in patients with ACS or cerebrovascular disease [1, 4, 5]. Our previous studies also showed that OSA was closely related to poor cardiovascular outcomes in ACS onset, especially regarding diabetes status [3, 20]. Emerging evidence has also demonstrated a close relationship between OSA and stroke. OSA is more prevalent following incident ischemic strokes since insults to the central nervous system result in changes in breathing patterns or could mask previously undiagnosed pre-stroke OSA in the poststroke period [30]. Moreover, several studies have demonstrated that OSA in poststroke patients is associated with an increased risk of recurrent ischemic stroke and worse outcomes [17, 18, 31]. Patients with untreated severe OSA are twice as likely to suffer an incident stroke, and this risk is especially relevant to younger and middle-aged patients, without a difference between men and women [32, 33]. In terms of mechanism, OSA may initiate and worsen atherosclerosis via the activation of oxidative stress, inflammation, the sympathetic nervous system, and metabolic abnormalities, eventually leading to high morbidity and mortality in cerebrovascular disease [34,35,36]. The ESADA Cohort demonstrated the role of OSA-related hypoxia in the risk of developing cardioembolic complications such as stroke [37]. Thus, OSA and stroke patients with ACS must be given extra attention, as they may exhibit a synergistic deleterious effect that increases future cardiovascular risk.

The benefits of CPAP therapy are well recognized: it eliminates obstructive events during sleep and substantially improves the consequences, especially daytime sleepiness, neurocognitive deficits and driving performance. However, in randomized controlled trials, the use of CPAP was not associated with a reduction in cardiovascular outcomes among patients with ACS [7,8,9,10]. Given that the phenotype of patients is not homogeneous, the deleterious effects of OSA could be different depending on the specific subgroups of ACS patients [38]. Therefore, it is important to focus on identifying specific subgroups of patients with ACS and reevaluate the effect of OSA treatment on cardiovascular diseases [39]. In particular, there is evidence suggesting that CPAP may improve sleepiness, neurological recovery, and depressive symptoms post-stroke in stroke survivors with OSA [19]. In our study, patients with OSA and prior stroke were at the increased risk of incurring a MACCE, therefore representing a high-risk subset most likely to respond to the intervention. There is no significant interaction between prior stroke and OSA for the combined or individual cardiovascular events, possibly due to the lack of power as a result of the small proportion of prior stroke group in this cohort and small number of events in a relatively short follow-up duration. This finding invites us to consider the possibility that a deleterious OSA effect, which was not observed in the entire population that suffered an ACS, exists in this specific phenotype. In contrast, the ancillary study of the ISAACC study showed that OSA was associated with an increased risk of recurrent cardiovascular events in patients without previous heart disease [23]. The variability of results might be partly explained by racial differences and suggests potential heterogeneity of ACS phenotype. We recruited predominantly East Asian patients, which cannot be generalized to patients with other ethnic or racial backgrounds. Noteworthy, patients in our study had more traditional risk factors and more severe daytime sleepiness than those in the ISAACC study [23]. Additionally, patients with prior stroke represents a high-risk subgroup with more female and more than 30% higher prevalence of all 3 traditional risk factors (hypertension, diabetes, hyperlipidemia), and had higher long-term events rate than those without prior stroke. Coexistence of these factors with OSA may generate synergistic effects and promote progression of lesions, thus increasing ischemic events in the long run [20, 40].

The premise of precision medicine is to use a variety of tools to differentiate an individual patient from other patients with similar clinical presentations and thus tailor treatments to that patient's particular needs. Hence, patients with ACS who previously had a stroke should be screened for OSA, and interventions may be necessary. Moreover, more OSA trials should be performed in this subgroup to determine the effects of OSA treatment.

Limitations

This study has several potential limitations. First, the prior stroke cohort included 207 patients, which may diminish the generalizability of the prognostic value. Second, the diagnosis of OSA based on portable sleep monitors may underestimate the severity of OSA. However, studies have shown that portable polygraphy can be used as an alternative to polysomnography for OSA diagnosis [41]. Third, patients self-reported their prior stroke history, which could result in some bias, and we could not confirm whether the strokes were hemorrhagic or ischemic. Therefore, the patients in our study received professional assistance to obtain admission information and conduct grouping, minimizing this bias. Finally, this study recruited predominantly East Asian patients, so it cannot be generalized to patients with other ethnic or racial backgrounds.

Conclusions

Among ACS patients, the presence of OSA was associated with an increased risk of cardiovascular events in patients with prior stroke. Further trials exploring the efficacy of OSA treatment in high-risk patients with ACS and prior stroke are warranted.

Availability of data and materials

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

Abbreviations

ACS:

Acute coronary syndrome

AHI:

Apnea–hypopnea index

BMI:

Body mass index

CPAP:

Continuous positive airway pressure

MACCE:

Major adverse cardiovascular and cerebrovascular event

NSTEMI:

Non-ST-segment elevation myocardial infarction

OSA:

Obstructive sleep apnea

STEMI:

ST-segment elevation myocardial infarction

References

  1. Lee C-H, Sethi R, Li R, Ho H-H, Hein T, Jim M-H, Loo G, Koo C-Y, Gao X-F, Chandra S, et al. Obstructive sleep apnea and cardiovascular events after percutaneous coronary intervention. Circulation. 2016;133:2008–17.

    Article  PubMed  Google Scholar 

  2. Johnson KG, Johnson DC. Frequency of sleep apnea in stroke and TIA patients: a meta-analysis. J Clin Sleep Med. 2010;6:131–7.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Fan J, Wang X, Ma X, Somers VK, Nie S, Wei Y. Association of obstructive sleep apnea with cardiovascular outcomes in patients with acute coronary syndrome. J Am Heart Assoc. 2019;8:e010826.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Yeghiazarians Y, Jneid H, Tietjens JR, Redline S, Brown DL, El-Sherif N, Mehra R, Bozkurt B, Ndumele CE, Somers VK. Obstructive sleep apnea and cardiovascular disease: a scientific statement from the American heart association. Circulation. 2021;144:e56–67.

    Article  CAS  PubMed  Google Scholar 

  5. Drager LF, McEvoy RD, Barbe F, Lorenzi-Filho G, Redline S. Sleep apnea and cardiovascular disease: lessons from recent trials and need for team science. Circulation. 2017;136:1840–50.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Martínez-García MA, Campos-Rodríguez F, Soler-Cataluña JJ, Catalán-Serra P, Román-Sánchez P, Montserrat JM. Increased incidence of nonfatal cardiovascular events in stroke patients with sleep apnoea: effect of CPAP treatment. Eur Respir J. 2012;39:906–12.

    Article  PubMed  Google Scholar 

  7. Yu J, Zhou Z, McEvoy RD, Anderson CS, Rodgers A, Perkovic V, Neal B. Association of positive airway pressure with cardiovascular events and death in adults with sleep apnea: a systematic review and meta-analysis. JAMA. 2017;318:156–66.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Sánchez-de-la-Torre M, Sánchez-de-la-Torre A, Bertran S, Abad J, Duran-Cantolla J, Cabriada V, Mediano O, Masdeu MJ, Alonso ML, Masa JF, et al. Effect of obstructive sleep apnoea and its treatment with continuous positive airway pressure on the prevalence of cardiovascular events in patients with acute coronary syndrome (ISAACC study): a randomised controlled trial. Lancet Respir Med. 2020;8:359–67.

    Article  PubMed  Google Scholar 

  9. McEvoy RD, Antic NA, Heeley E, Luo Y, Ou Q, Zhang X, Mediano O, Chen R, Drager LF, Liu Z, et al. CPAP for prevention of cardiovascular events in obstructive sleep apnea. N Engl J Med. 2016;375:919–31.

    Article  PubMed  Google Scholar 

  10. Peker Y, Glantz H, Eulenburg C, Wegscheider K, Herlitz J, Thunström E. Effect of positive airway pressure on cardiovascular outcomes in coronary artery disease patients with nonsleepy obstructive sleep apnea. the RICCADSA randomized controlled trial. Am J Respir Crit Care Med. 2016;194:613–20.

    Article  CAS  PubMed  Google Scholar 

  11. Mukherjee D, Eagle KA, Kline-Rogers E, Feldman LJ, Juliard J-M, Agnelli G, Budaj A, Avezum A, Allegrone J, FitzGerald G, Steg PG. Impact of prior peripheral arterial disease and stroke on outcomes of acute coronary syndromes and effect of evidence-based therapies (from the global registry of acute coronary events). Am J Cardiol. 2007;100:1–6.

    Article  PubMed  Google Scholar 

  12. Ducrocq G, Amarenco P, Labreuche J, Alberts MJ, Mas J-L, Ohman EM, Goto S, Lavallée P, Bhatt DL, Steg PG. A history of stroke/transient ischemic attack indicates high risks of cardiovascular event and hemorrhagic stroke in patients with coronary artery disease. Circulation. 2013;127:730–8.

    Article  PubMed  Google Scholar 

  13. Xu J-J, Jia S-d, Zhu P, Jiang L, Jiang P, Song Y, Zhao X-Y, Li J-X, Chen J, Yang Y-J, et al. Does prior stroke predict long-term recurrent stroke after percutaneous coronary intervention? five-year results from a large cohort study. Front Neurol. 2021;12:740136.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Zhang D, Song X, Chen Y, Raposeiras-Roubín S, Abu-Assi E, Henriques JPS, D’Ascenzo F, Saucedo J, González-Juanatey JR, Wilton SB, et al. Outcome of patients with prior stroke/transient ischemic attack and acute coronary syndromes. Angiology. 2020;71:324–32.

    Article  PubMed  Google Scholar 

  15. Sposato LA, Hilz MJ, Aspberg S, Murthy SB, Bahit MC, Hsieh C-Y, Sheppard MN, Scheitz JF. Post-stroke cardiovascular complications and neurogenic cardiac injury: JACC state-of-the-art review. J Am Coll Cardiol. 2020;76:2768–85.

    Article  PubMed  Google Scholar 

  16. Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, Mohsenin V. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med. 2005;353:2034–41.

    Article  CAS  PubMed  Google Scholar 

  17. Parra O, Sánchez-Armengol A, Bonnin M, Arboix A, Campos-Rodríguez F, Pérez-Ronchel J, Durán-Cantolla J, de la Torre G, González Marcos JR, de la Peña M, et al. Early treatment of obstructive apnoea and stroke outcome: a randomised controlled trial. Eur Respir J. 2011;37:1128–36.

    Article  CAS  PubMed  Google Scholar 

  18. Brown DL, Shafie-Khorassani F, Kim S, Chervin RD, Case E, Morgenstern LB, Yadollahi A, Tower S, Lisabeth LD. Sleep-disordered breathing is associated with recurrent ischemic stroke. Stroke. 2019;50:571–6.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Bassetti CLA, Randerath W, Vignatelli L, Ferini-Strambi L, Brill A-K, Bonsignore MR, Grote L, Jennum P, Leys D, Minnerup J, et al. EAN/ERS/ESO/ESRS statement on the impact of sleep disorders on risk and outcome of stroke. Eur Respir J. 2020. https://doi.org/10.1183/13993003.01104-2019.

    Article  PubMed  Google Scholar 

  20. Wang X, Fan J, Du Y, Ma C, Ma X, Nie S, Wei Y. Clinical significance of obstructive sleep apnea in patients with acute coronary syndrome in relation to diabetes status. BMJ Open Diabetes Res Care. 2019;7:e000737.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Xie J, Sert Kuniyoshi FH, Covassin N, Singh P, Gami AS, Wang S, Chahal CAA, Wei Y, Somers VK. Nocturnal hypoxemia due to obstructive sleep apnea is an independent predictor of poor prognosis after myocardial infarction. J Am Heart Assoc. 2016. https://doi.org/10.1161/JAHA.115.003162.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Kuniyoshi FHS, Garcia-Touchard A, Gami AS, Romero-Corral A, van der Walt C, Pusalavidyasagar S, Kara T, Caples SM, Pressman GS, Vasquez EC, et al. Day-night variation of acute myocardial infarction in obstructive sleep apnea. J Am Coll Cardiol. 2008;52:343–6.

    Article  PubMed  Google Scholar 

  23. Zapater A, Sánchez-de-la-Torre M, Benítez ID, Targa A, Bertran S, Torres G, Aldomà A, De Batlle J, Abad J, Duran-Cantolla J, et al. The effect of sleep apnea on cardiovascular events in different acute coronary syndrome phenotypes. Am J Respir Crit Care Med. 2020;202:1698–706.

    Article  PubMed  Google Scholar 

  24. Price S, Katz J, Kaufmann CC, Huber K. The year in cardiovascular medicine 2021: acute cardiovascular care and ischaemic heart disease. Eur Heart J. 2022;43:800–6.

    Article  CAS  PubMed  Google Scholar 

  25. Escaned J, Jaffer FA, Mehilli J, Mehran R. The year in cardiovascular medicine 2021: interventional cardiology. Eur Heart J. 2022;43:377–86.

    Article  CAS  PubMed  Google Scholar 

  26. Hicks KA, Tcheng JE, Bozkurt B, Chaitman BR, Cutlip DE, Farb A, Fonarow GC, Jacobs JP, Jaff MR, Lichtman JH, et al. 2014 ACC/AHA key data elements and definitions for cardiovascular endpoint events in clinical trials: a report of the American college of cardiology/American heart association task force on clinical data standards (writing committee to develop cardiovascular endpoints data standards). J Am Coll Cardiol. 2015;66:403–69.

    Article  PubMed  Google Scholar 

  27. Cooper HA, Domanski MJ, Rosenberg Y, Norman J, Scott JH, Assmann SF, McKinlay SM, Hochman JS, Antman EM. Acute ST-segment elevation myocardial infarction and prior stroke: an analysis from the magnesium in coronaries (MAGIC) trial. Am Heart J. 2004;148:1012–9.

    Article  PubMed  Google Scholar 

  28. Colantonio LD, Gamboa CM, Kleindorfer DO, Carson AP, Howard VJ, Muntner P, Cushman M, Howard G, Safford MM. Stroke symptoms and risk for incident coronary heart disease in the REasons for Geographic and racial differences in stroke (REGARDS) study. Int J Cardiol. 2016;220:122–8.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Sposato LA, Fridman S, Whitehead SN, Lopes RD. Linking stroke-induced heart injury and neurogenic atrial fibrillation: a hypothesis to be proven. J Electrocardiol. 2018. https://doi.org/10.1016/j.jelectrocard.2018.02.006.

    Article  PubMed  Google Scholar 

  30. Koo DL, Nam H, Thomas RJ, Yun C-H. Sleep disturbances as a risk factor for stroke. J Stroke. 2018;20:12–32.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Javaheri S, Peker Y, Yaggi HK, Bassetti CLA. Obstructive sleep apnea and stroke: the mechanisms, the randomized trials, and the road ahead. Sleep Med Rev. 2022;61:101568.

    Article  PubMed  Google Scholar 

  32. Chang C-C, Chuang H-C, Lin C-L, Sung F-C, Chang Y-J, Hsu CY, Chiang L-L. High incidence of stroke in young women with sleep apnea syndrome. Sleep Med. 2014;15:410–4.

    Article  PubMed  Google Scholar 

  33. Lamberts M, Nielsen OW, Lip GYH, Ruwald MH, Christiansen CB, Kristensen SL, Torp-Pedersen C, Hansen ML, Gislason GH. Cardiovascular risk in patients with sleep apnoea with or without continuous positive airway pressure therapy: follow-up of 4.5 million danish adults. J Int Med. 2014;276:659–66.

    Article  CAS  Google Scholar 

  34. Javaheri S, Barbe F, Campos-Rodriguez F, Dempsey JA, Khayat R, Javaheri S, Malhotra A, Martinez-Garcia MA, Mehra R, Pack AI, et al. Sleep apnea: types, mechanisms, and clinical cardiovascular consequences. J Am Coll Cardiol. 2017;69:841–58.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Cowie MR. Sleep apnea: state of the art. Trends Cardiovasc Med. 2017;27:280–9.

    Article  PubMed  Google Scholar 

  36. Liu B, Li Y, Du J, She Q, Deng S. Epicardial adipose tissue in patients with obstructive sleep apnea: a systematic review and meta-analysis. Cardiovasc Innov Appl. 2020;000:81–8.

    Google Scholar 

  37. Pengo MF, Faini A, Grote L, Ludka O, Joppa P, Pataka A, Dogas Z, Mihaicuta S, Hein H, Anttalainen U, et al. Impact of sleep apnea on cardioembolic risk in patients with atrial fibrillation: data from the ESADA cohort. Stroke. 2021;52:712–5.

    Article  CAS  PubMed  Google Scholar 

  38. Martinez-Garcia MA, Campos-Rodriguez F, Gozal D. Obstructive sleep apnoea in acute coronary syndrome. Lancet Respir Med. 2020;8:e15.

    Article  PubMed  Google Scholar 

  39. Peker Y. Obstructive sleep apnoea in acute coronary syndrome. Lancet Respir Med. 2020;8:e14.

    Article  PubMed  Google Scholar 

  40. Wang X, Fan J, Guo R, Hao W, Gong W, Yan Y, Zheng W, Ai H, Que B, Hu D, et al. Association of OSA with cardiovascular events in women and men with acute coronary syndrome. Eur Respir J. 2022. https://doi.org/10.1183/13993003.01110-2022.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Corral J, Sánchez-Quiroga M-Á, Carmona-Bernal C, Sánchez-Armengol Á, de la Torre AS, Durán-Cantolla J, Egea CJ, Salord N, Monasterio C, Terán J, et al. Conventional Polysomnography Is Not Necessary for the Management of Most Patients with Suspected Obstructive Sleep Apnea. Noninferiority, Randomized Controlled Trial. Am J Respir Crit Care Med. 2017;196:1181–90.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

Thanks to Drs Ruifeng Guo, Xin Huang, Zexuan Li, Siyi Li and Ge Wang for collecting study data (Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China).

Funding

This study was funded by grants from National Natural Science Foundation of China (81870322), the Natural Science Foundation of Beijing, China (7191002, 7222046), National Key R&D Program of China (2020YFC2004800), and Beijing Nova Program (Z201100006820087).

Author information

Authors and Affiliations

Authors

Contributions

Study concept and design: BW, XW, SN. Acquisition, analysis, or interpretation of data: BW, WH, JF, YY, WG, WZ. Drafting of the manuscript: BW. Critical revision of the manuscript for important intellectual content: All authors. Obtained funding: XW, SN. Administrative, technical, or material support: BQ, HA, XW, SN. BW, XW, SN had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Xiao Wang or Shaoping Nie.

Ethics declarations

Ethics approval and consent to participate

The study was approved by the Institutional Review Board of Beijing Anzhen Hospital, Capital Medical University (2013025) and all patients provided written informed consent.

Consent for publication

All the authors consent to the publication of the manuscript.

Competing interests

Dr. Shaoping Nie: research grants to the institution from Boston Scientific, Abbott, Jiangsu Hengrui Pharmaceuticals, China Resources Sanjiu Medical & Pharmaceuticals, East China Pharmaceuticals. The other authors disclose no conflicts of interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1: Table S1.

Baseline patient characteristics. Table S2. Crude Number of all Events by Prior Stroke Categories. Table S3. Association of OSA with risk of MACCE according to subgroups. Fig. S1. Kaplan-Meier curves for the analysis of cardiovascular events in prior stroke versus non-prior stroke group. Fig. S2. Kaplan-Meier curves for the analysis of cardiovascular events according to obstructive sleep apnea severity in prior stroke (A) versus non-prior stroke group (B).

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, B., Hao, W., Fan, J. et al. Clinical significance of obstructive sleep apnea in patients with acute coronary syndrome with or without prior stroke: a prospective cohort study. Eur J Med Res 28, 107 (2023). https://doi.org/10.1186/s40001-023-01071-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s40001-023-01071-0

Keywords