Sleep Disordered-Breathing and Aortic Valve Stenosis: A Systematic Review and Meta-Analysis

Heba Ramadan

doi:10.17241/smr.2025.03188

Abstract

Background and Objective

Sleep-disordered breathing (SDB), including obstructive sleep apnea (OSA) and central sleep apnea (CSA), is common in older adults and linked to cardiovascular disease. Aortic stenosis (AS), is another prevalent condition in this population. The interaction between SDB and AS remains unclear, particularly regarding outcomes after surgical aortic valve replacement or transcatheter aortic valve implantation. This review systematically examines the prevalence, clinical impact, and potential bidirectional relationship between SDB and AS.

Methods

Following PRISMA guidelines, multiple databases were searched. Eligible observational studies included adults with both AS and SDB, reporting prevalence or comparative outcomes. Data extraction included study characteristics, diagnostic methods, interventions, and prevalence estimates. Quality assessment employed JBI and Newcastle-Ottawa tools. Meta-analyses were performed using odds ratios (OR), standardized mean differences, and prevalence estimates with random or fixed effects models based on heterogeneity.

Results

A total of 11 studies met inclusion criteria (9 prevalence-focused, 2 comparative). Pooled prevalence of SDB in AS patients was 76% (95% confidence interval [CI]: 63%–89%). Both OSA (49%) and CSA (51%) were observed. Male sex was more common among patients with SDB (OR=1.68, 95% CI: 1.07–2.62). Body mass index (BMI) tended to be higher in OSA than CSA, though not consistently significant. In comparative analyses, patients with SDB showed higher odds of AS (OR=1.16, 95% CI: 1.14–1.17).

Conclusions

SDB is highly prevalent in AS and may contribute to disease progression. Findings suggest a possible bidirectional association influenced by sex and BMI. Larger well-matched cohorts with long-term follow-up before and after valve interventions are needed to clarify causality and treatment effects.

Key words: Sleep apnea, Aortic stenosis, Obstructive sleep apnea, Central sleep apnea, Aortic valve disease, Apnea-Hypopnea Index

INTRODUCTION

Sleep-disordered breathing (SDB) represents a spectrum of conditions characterized by recurrent disturbances in ventilation during sleep, most commonly obstructive sleep apnea (OSA), central sleep apnea (CSA), and mixed forms. These disorders are usually diagnosed by polysomnography, with the apnea-hypopnea index (AHI) serving as the standard measure. An AHI of 5–14 events per hour indicates mild disease, 15–19 defines moderate disease, and ≥30 reflects severe disease. Beyond their impact on quality of life, SDB has been linked to a wide range of cardiovascular complications [1,2].

Aortic stenosis (AS) is one of the most prevalent valvular heart diseases, particularly in the elderly population. AS is characterized by progressive narrowing of the aortic valve due to degenerative changes, most commonly fibrosis and calcification, leading to increased left ventricular outflow obstruction and adverse cardiovascular outcomes. In recent decades, surgical aortic valve replacement (SAVR) and the less invasive transcatheter aortic valve implantation (TAVI) have become the mainstay interventions for advanced cases [3]. However, the interaction between these procedures and SDB is not fully understood. Some studies report improvement in sleep apnea after valve intervention, whereas others describe persistence or even worsening of sleep-related breathing disturbances. Furthermore, the presence of SDB before intervention may predispose patients to higher complications and poor recovery outcomes [4,5].

This complex interplay suggests a potential bidirectional relationship: AS may contribute to the development or exacerbation of SDB through mechanisms such as increased left atrial pressure, pulmonary congestion, and altered autonomic regulation, while SDB may accelerate the progression of AS by promoting hypertension, systemic inflammation, and endothelial dysfunction. Given the high prevalence of both conditions in older adults, exploring these connections is of a particular clinical importance.

Although several systematic reviews have investigated associations between cardiovascular diseases and sleep disorders in general, none have specifically addressed SDB in the context of AS [2,6]. The present study aims to fill this gap by systematically reviewing and quantitatively analyzing the evidence on the prevalence, clinical impact, and potential bidirectional links between these two conditions.

METHODS

This review was conducted in accordance with the PRISMA framework to maintain a clear, systematic, and reproducible methodology.

Data Sources and Searches

On July 11, 2025, a comprehensive search of the literature was performed using multiple databases, including Scopus, MEDLINE, PubMed, and Google Scholar. The search strategy included terms such as sleep-disordered breathing, sleep apnea, obstructive sleep apnea, central sleep apnea, Apnea-Hypopnea Index, OSA, CSA, aortic stenosis, aortic valve stenosis, aortic valve calcification, severe aortic stenosis, and aortic valve disease.

Inclusion and Exclusion Criteria

Studies were considered eligible for inclusion if they employed an observational design and involved adult participants diagnosed with both AS and SDB. Given that AS primarily affects older populations, only studies conducted in adults were included. To ensure quantitative synthesis, studies examining AS were required to specify how many patients had coexisting SDB. Likewise, studies on SDB had to report the total number and indicate how many were diagnosed with AS. In comparative studies, it was essential that similar data were available for the control group.

Studies were excluded if they were conducted on animals, presented as case reports, narrative or systematic reviews, or did not clearly differentiate AS from other cardiovascular conditions. Research that discussed other forms of aortic narrowing such as abdominal stenosis was excluded as the focus of this review was strictly limited to valvular involvement. Studies addressing sleep disturbances not related to breathing such as insomnia or general sleep quality were also excluded unless SDB was specifically reported with numerical data. Additionally, studies involving patients with advanced comorbid conditions like heart failure, or those that failed to account for confounding variables such as diabetes and hypertension, were not considered. This was to avoid potential bias in interpreting the association between the two conditions of interest.

Study Selection

The study selection proceeded in two phases: first, titles and abstracts were screened to identify potentially relevant studies; next, full-text articles were reviewed in detail to confirm their eligibility.

Data Extraction and Quality Assessment

Data extraction focused on several key variables, including the first author’s name, year of publication, country of study, publishing journal, study design, and study period. Additional details recorded were the mean age of participants, percentage of males, study setting (monocenter or multicenter), diagnostic methods used for identifying SDB, and the specific type of SDB examined. For studies involving treatment, any reported interventions for aortic valve stenosis such as surgical or transcatheter valve replacement were noted. Furthermore, data were extracted on the number of participants with AS and their coexisting SDB, and vice versa for participants with SDB diagnosed with AS. In comparative studies, corresponding data were also gathered for the control groups.

The quality of group 1 studies was evaluated using the JBI Critical Appraisal checklist for Prevalence Studies (Supplementary Table 1 in the online-only Data Supplement). The JBI tool evaluates prevalence studies across multiple domains, including the appropriateness of the sample frame, sampling method, sample size, description, data coverage, diagnostic criteria, measurements, statistical analysis, and response rate. The scores ranged from 7 to 9 across the included studies, indicated high methodological quality. For group 2 studies, which were comparative in design, quality assessment was conducted with the Newcastle-Ottawa Scale (NOS) for case-control studies (Supplementary Table 2 in the online-only Data Supplement). The NOS assesses case-control studies based on the selection of study groups, comparability between groups, and ascertainment of outcomes or exposure. The included studies receiving scores of 7 and 8, reflecting the good methodological quality. In this review, each study was independently scored according to the relevant tool, and the results were used to guide the interpretation of findings.

Data Synthesis and Analysis

Meta-analysis was conducted using R version 4.3.2 (R Foundation for Statistical Computing). For continuous variables, standardized mean differences (SMD) with 95% confidence intervals (CIs) were calculated, while pooled odds ratios (ORs) were derived for categorical outcomes. Heterogeneity across studies was assessed using the I² statistic and Cochran’s Q test (with p<0.05 indicating significant heterogeneity), where substantial heterogeneity (I²>50% and/or p<0.05) was observed, a random-effects model was applied; otherwise, a fixed-effect model was used.

RESULTS

Literature Search

A systematic search was conducted across: MEDLINE (n=48), Scopus (n=27), PubMed (n=120), and Google Scholar (n=2, identified manually). This yielded a total of 197 studies. After removing 60 duplicates, 137 studies were screened based on their titles and abstracts.

During this initial screening phase, 120 studies were excluded for various reasons, including irrelevance to the research outcome, being review articles or case reports. The remaining 17 articles were selected for full-text review. Following a more detailed evaluation, 5 studies were excluded due to failure to meet the eligibility criteria. A total of 12 full-text articles were assessed for eligibility, and one was excluded for not addressing the primary outcome.

Ultimately, 11 studies met all inclusion criteria and were included in the final review (Fig. 1).

Group 1 Studies

This group comprised nine studies [4,5,7–13] investigating the prevalence of sleep-related breathing disorders in patients with AS (Supplementary Table 3 in the online-only Data Supplement), published between 2011 and 2025. Five were conducted in Germany, while the remaining studies originated from Mexico, the USA, Thailand, and Japan. The articles appeared in reputable journals, including Biomedicines, Sleep Advances, Journal of the Medical Association of Thailand, Circulation Reports, Clinical Intervention in Aging, PLoS One, Clinical Research in Cardiology, EuroIntervention, and the Postgraduate Medical Journal.

Study designs were predominantly prospective, although cross-sectional designs were also reported. All were carried out in single-center setting and involved elderly populations aged between 60 and 80 years. Male representation varied widely, with several studies reporting a higher proportion of men in the SDB subgroup.

The type of sleep disorder varied across studies, including OSA, CSA, and mixed forms collectively referred to as SDB. Diagnostic methods included objective measures such as AHI (threshold >5 events/hour) and screening tools like the STOP-Bang questionnaire.

Although the included studies were not originally designed as comparative analyses, they assessed the prevalence of SDB among patients with AS. This naturally yielded two groups, those with sleep disorders and those without, which were subsequently compared. However, the nature of these comparisons varied across studies. In some, the analysis was between patients with and without SDB (studies 1, 3, 4, 5, 6, 9). Others focused solely on patients with SDB, comparing severity categories such as mild, moderate, and severe (study 2). Some studies contrasted OSA with CSA (study 7), while others concentrated on CSA and compared it with both other types of sleep apnea and the absence of SDB (study 8).

Baseline characteristics and comorbidity profiles were generally similar between patients with and without SDB in most studies. However, even after adjustment for comorbidities, some investigations examined body mass index (BMI). One study (study 4) reported a significant BMI difference between participants with and without SDB, whereas another (study 2) found significant BMI differences across SDB severity subgroups–mild, moderate, and severe.

The timing of assessments varied: some studies evaluated patients prior to TAVI (studies 3, 5, 6, 8, 9), others after SAVR (studies 1, 2), and only study 7 included both pre- and post-procedure evaluations. In addition, study 4 assessed patients following TAVI.

The meta-analysis findings revealed that across AS patients, the pooled male proportion (studies 1, 2, 3, 4, 5, 6, 8, 9) was 48% (95% CI: 39%–58%). Among those with SDB, the male proportion (studies 1, 2, 4, 6, 7) was 55% (95% CI: 44%–65%). The odds of being male were significantly higher in patients with SDB compared with those without SDB (OR=1.68, 95% CI: 1.07–2.62) (Fig. 2).

The overall prevalence of SDB in AS patients was 76% (95% CI: 63%–89%) (Fig. 3). Subgroup analyses indicated that Pre-TAVI patients (studies 3, 5, 6, 7a, 8, 9) had a prevalence of 81% (95% CI: 71%–90%) (Supplementary Fig. 1 in the online-only Data Supplement), while post-TAVI patients (studies 4, 7b) showed a prevalence of 64% (95% CI: 5%–100%) (Supplementary Fig. 2 in the online-only Data Supplement). Post-SAVR patients (studies 1, 2) exhibited a prevalence of 85% (95% CI: 58%–100%) (Supplementary Fig. 3 in the online-only Data Supplement), and when considering Post-intervention data (SAVR/TAVI; studies 1, 2, 4, 7b), the prevalence was 74% (95% CI: 45%–100%) (Supplementary Fig. 4 in the online-only Data Supplement).

Regarding SDB severity (studies 2, 5, 6, 8) (Supplementary Table 4 in the online-only Data Supplement) mild cases accounted for 38% (95% CI: 32%–45%) (Supplementary Fig. 5 in the online-only Data Supplement), moderate cases 34% (95% CI: 27%–41%) (Supplementary Fig. 6 in the online-only Data Supplement), and severe cases 30% (95% CI: 23%–37%) (Supplementary Fig. 7 in the online-only Data Supplement).

Analysis by SDB type (studies 6, 7, 8, 9) showed that OSA accounted for 49% (95% CI: 34%–63%) (Supplementary Fig. 8 in the online-only Data Supplement), while CSA accounted for 51% (95% CI: 37%–66%) (Supplementary Fig. 9 in the online-only Data Supplement).

Finally, the SMD in BMI between OSA and CSA (studies 6, 7a) was 0.27 (95% CI: −0.04–0.58), indicating a slightly increased BMI in the OSA group, although the difference was not statistically significant (Supplementary Table 5 and Supplementary Fig. 10 in the online-only Data Supplement).

Group 2 Studies

It comprised two comparative studies [14,15] that began with patients classified into sleep disorders and no sleep disorders groups, then investigated the presence of AS in both (Supplementary Table 6 in the online-only Data Supplement). Published in 2025 and 2021 in the USA and Italy, respectively. The U.S. study was a large multicenter analysis using data from the TriNetX Diamond Network and All of US registries, focusing primarily on sleep apnea as a potential risk factor for aortic stenosis. The Italian study was a single-center observational analysis comparing the prevalence of AS and other valvular heart diseases between the two groups (with and without sleep apnea).

The meta-analysis findings indicated that among patients with sleep disorders, the pooled male proportion was 56% (37%–75%) (Supplementary Fig. 11 in the online-only Data Supplement). Although the odds indicated a higher proportion in the sleep disorders group, this association was not statistically significant (OR=1.08, 95% CI: 0.94–1.24) (Supplementary Fig. 12 in the online-only Data Supplement).

Patients with sleep disorders also demonstrated a significantly higher BMI than controls, with a pooled SMD of 0.64 (0.49–0.78) (Fig. 4).

Regarding AS prevalence, the pooled prevalence of AS in patients with sleep disorders was 2% (95% CI: 1%–3%). The odds of AS were significantly higher in this group compared with controls (OR=1.16, 95% CI: 1.14–1.17) (Fig. 5).

DISCUSSION

This systematic review and meta-analysis provide quantitative evidence supporting a potential bidirectional association between AS and SDB. Across included studies, a remarkably high prevalence of SDB was identified among patients with AS, with pooled estimates approaching 76%. Subgroup analyses demonstrated that both OSA (49%) and CSA (51%) were common. Severity distributions revealed that mild cases (38%) were more common than moderate cases (34%) and severe cases (30%). In addition, patients with SDB were more likely to be male, and higher BMI showed a modest association with the prevalence of sleep apnea, consistent with established risk factors for OSA.

These findings align with prior research linking SDB to cardiovascular pathology more broadly [2,6]. Previous systematic reviews have consistently documented strong associations between SDB and coronary artery disease, arrhythmias, and heart failure [16]. Unlike those analyses, the present review focused specifically on AS, a valvular condition not previously examined in this context through pooled analysis. Supporting this, large database analyses have suggested that patients with sleep apnea face a higher risk of developing valvular diseases, including AS, compared with individuals without SDB [14]. Pooled data from comparative studies reinforced this observation, demonstrating that patients with sleep disorders had significantly greater odds of being diagnosed with AS.

However, this observation must be interpreted with caution, as the pooled OR was derived from a small number of comparative studies, and these analyses primarily relied on registry-based datasets using ICD diagnostic codes. Such databases may be susceptible to diagnostic misclassification and incomplete adjustment for confounding variables, which could affect the accuracy of the estimated association. Therefore, these findings should be viewed as preliminary, requiring validation in large studies using clinically confirmed diagnostic criteria.

One potential explanation for this link lies in the pathophysiology of AS itself. Calcification of the aortic valve, the hallmark of degenerative AS, may progress more rapidly in the presence of systematic inflammation and oxidative stress, mechanisms that are commonly heightened in SDB. As some studies have reported, this could partly explain the development of more severe forms of AS in patients with SDB [17].

The high prevalence of SDB among AS patients is also noteworthy in the context of interventions. Stratified analyses revealed prevalence of 85% after SAVR and 81% in pre-TAVI patients, while post-TAVI prevalence appeared lower at 64%, though based on heterogeneous and limited data. When post-SAVR and post-TAVI were combined, prevalence was 74%, remaining lower than post-SAVR alone. Interestingly, in the single study (study 7) that assessing patients before and after TAVI, prevalence was extremely high at baseline (95%) and remained high post procedure (94%), with only a slight decrease. These findings suggest that intervention type may influence outcomes: SAVR appears linked to persistent or even increased prevalence of SDB, whereas TAVI might reduce it modestly, though inconsistently. Overall, evidence remains mixed, with some studies reporting improvement.

Nevertheless, some limitations should be recognized. The current evidence is based on a relatively small pool of studies, which restricts the robustness of the conclusions. In many investigations, the comparative groups were defined only after identifying SDB among patients with AS, meaning that the initial design did not always include direct comparisons between SDB and non-SDB groups. Moreover, several studies concentrated exclusively on patients with SDB and its severity categories, rather than contrasting them with unaffected individuals. Interventional studies also varied, with only one examining changes in SDB prevalence before and after the procedure, while most did not assess this aspect. As a result, heterogeneity across findings needs to be considered. Another issue is that the majority of studies were conducted in Germany, which may limit generalizability. Finally, most investigations assessed short or intermediate term outcomes, leaving the long-term course of SDB following valve intervention insufficiently understood.

Future research is warranted to clarify the mechanisms linking SDB with AS, including systemic inflammation and valve calcification. Well-designed comparative cohorts are necessary to further explore this association. Long-term follow-up before and after interventions is needed to assess whether treatment type affects outcomes. Further research should also examine whether sleep apnea is an independent risk factor, with attention to disease severity, sex differences, and BMI.

In conclusion, this meta-analysis highlights a potential bidirectional association between AS and SDB. The prevalence of SDB was notable among patients with AS, with some interventions appearing to further increase the risk. OSA and CSA were the most commonly investigated subtypes. The severity of SDB varied, with mild cases showing a relatively high frequency. Male sex was predominant among individuals with SDB and those with combined AS and SDB. BMI may play a relevant role. Future studies should employ well-matched comparative studies between AS patients and controls to better clarify this relationship. Research is also needed to assess patients both before and after different interventions (such as TAVI and SAVR) to determine whether treatment type influences the incidence or progression of SDB, with adequate follow-up durations to capture long-term outcomes. More investigations are warranted to confirm whether sleep disorders, particularly sleep apnea, represent independent risk factors for AS. Greater attention to disease severity (both SDB and AS), sex differences, and BMI is essential.