Keywords
otolaryngology - sleep apnea - cardiovascular disease - sleep medicine specialty -
CPAP
Question
Is CPAP the key to reduce the CV risk in OSA patients?
Introduction
Obstructive sleep apnea (OSA) is a common condition among the general population,
and the CPAP treatment is the standard first-line therapy. There has been significant
debate over whether OSA increases the predisposition to develop cardiovascular disease
(CVD); however, though the data are conflicting, most physicians would recommend the
treatment of OSA to reduce CVD risk. In the present paper, we aim to examine if the
CPAP treatment is the best practice to reduce the risk of developing CVD in OSA patients.
Literature Review
In 2023, Labarca et al.[1] published an extensive study on the incidence of cardiovascular (CV) morbidity and
mortality among patients who experience the physiological burdens of OSA, which include
hypoxic burden (HB), ventilatory burden (VB), ventilatory deficit, and arousal burden.
The authors used the Multi-Ethnic Study of Atherosclerosis (MESA) and the Osteoporotic
Fractures in Men (MrOS) study to quantify the impact of OSA on the CV risk. These
studies had a cumulative sample size of 4,600 patients. In the primary analysis, the
MESA study showed that every standard deviation increase in the HB led to an increase
of 45% in the risk of incident CVD events, and, in the MrOS study, there was a 13%
increased risk. Further, for the VB, in the MESA study, there was a 35% increased
risk, and, in the MrOS study, 12%. Though the VB can predict the CVD risk in OSA patients,
the MESA and MrOS studies show that the HB more strongly correlates to the CVD risk.
Labarca et al.[1] demonstrated that the HB is a strong predictor of increased CVD risk in OSA patients.
In 2016, Guo et al.[2] conducted a meta-analysis which included 18 randomized clinical trials (RCTs), with
a total sample size of 4,146 patients. They evaluated the risk of CVD events and mortality
among OSA patients treated with CPAP. Additionally, they assessed the effect of CPAP
on the Epworth Sleepiness Score (ESS) and blood pressure (BP), both of which may contribute
to CVD. The CPAP treatment significantly decreased the ESS. Regarding BP, the CPAP
therapy significantly lowered both systolic and diastolic BP compared with the control
groups. There was a significant decrease in the daytime and nocturnal diastolic BP
and a decrease in the nocturnal systolic BP. Additionally, Guo et al.[2] found that CPAP had a mild beneficial effect on CV events in patients who used it
for ≥ 4 hours per night and, with longer treatment, it also decreased CV mortality
to levels similar to those of patients without OSA. Overall, this meta-analysis suggests
that CPAP is a safe and effective treatment for OSA patients, and that the CPAP therapy
is associated with a trend of decreased risk of CVD events.
In 2016, Peker et al.[3] conducted an RCT with 244 patients to investigate the relationship between OSA and
coronary artery disease (CAD), is a common subtype of CVD with a high mortality risk.
Obstructive sleep apnea is also a common condition in patients with CAD, but it often
goes undiagnosed. The primary endpoint in this trial was the first event of repeat
revascularization, myocardial infarction, stroke, or CV mortality. In the on-treatment
analysis, there was a significant difference between the groups in the incidence rates
based on CPAP use for ≥ 4 hours per night. Their findings suggest that CPAP use for > 4 hours
per night was associated with a reduced risk of the composite endpoint in patients
with CAD and OSA after adjustment for baseline comorbidities and compliance with the
treatment.
In 2018, Khan et al.[4] conducted a meta-analysis on the relationship between OSA and CV events and the
efficacy of CPAP therapy in alleviating OSA. The authors first looked at the Sleep
Apnea Cardiovascular Endpoints (SAVE) trial, an RCT which aimed to determine whether
the CPAP treatment for OSA could reduce the risk of presenting serious CV events.
In its original findings, the SAVE trial reported that the CPAP therapy did not significantly
reduce the risk of presenting CV events. However, upon further analysis, Khan et al.[4] adjusted for better compliance time (≥ 4 hours per night) and ultimately found a
non-significant trend favoring the CPAP therapy. The results of the meta-analysis
showed that, though further randomized trials are required, a significant risk reduction
in major adverse CV events was observed in the sensitivity analyses excluding two
studies with low CPAP adherence time per night and the results from the SAVE trial.
In 2021, Wickwire et al.[5] performed a retrospective study to further understand the efficacy of the CPAP treatment
in preventing CV events in OSA patients. They used a 5% random sample of Medicare
administrative records from 2008 to 2015, generating a population of 5,024 Medicare
beneficiaries, with an average age of 72 years. The cohort consisted of individuals
with OSA submitted to at least 1 session of the CPAP treatment within 6 months of
the diagnosis. Additionally, the cohort presented a high prevalence of CVD and CVD
morbidities. Wickwire et al.[5] determined that adherence to the CPAP treatment significantly reduced the risk of
presenting new CVD events. Further, the authors found that the CPAP treatment reduced
the incidence of new CVD events over 25 months. Subjects undergoing ≥ 4 hours per
night of CPAP presented a more significant decrease in new CVD events compared to
individuals who underwent < 4 hours per night of CPAP. This study sheds light on the
potential advantages of consistent CPAP therapy in lowering the chances of experiencing
CV events among the elderly.
Conclusion
Currently, no RCTs conclusively demonstrate that CPAP reduces the incidence of CV.
While the data suggest that CPAP may lower the CV risk in OSA patients, this benefit
has been observed primarily in subgroup analyses. The CPAP treatment has been shown
to reduce BP and improve sleepiness, both of which are pathways that could potentially
reduce the CV risk. Therefore, with high CPAP compliance, there is a possibility of
reducing the CVD risk. Although further studies are needed to confirm these findings
among with consistent high compliance to the CPAP treatment, it remains reasonable
to continue to prescribe CPAP as the first-line therapy for OSA due to its potential
CV benefits and low associated risks.
Level of Evidence
Studies regarding OSA and the treatment for OSA to reduce CVD risk vary in terms of
the level of evidence. The present literature review focuses on 5 studies, which are
summarized in [Table 1]. Three of the studies[2]
[4]
[5] have level 2 of evidence, and two[1]
[3] have level 1.
Table 1
Summary of the studies on the efficacy of the CPAP therapy
|
Study title
|
Level of evidence
|
Summary
|
Sample size
|
|
Sleep
apnea physiological burdens and cardiovascular morbidity and mortality.
|
Level 1
|
Found that the hypoxic burden is a strong predictor of increased cardiovascular disease
risk in OSA patients.
|
4,600 patients
|
|
Effects of CPAP therapy on cardiovascular events and mortality in patients with OSA:
a meta-analysis.
|
Level 2
|
Highlights the positive impact of the CPAP treatment on OSA patients, revealing significant
improvements in sleepiness levels and blood pressure, and suggests a potential decrease
in CV events associated with longer-term CPAP use.
|
4,146 patients
|
|
Effect of positive airway pressure on cardiovascular outcomes in coronary artery disease
patients with nonsleepy obstructive sleep apnea. The RICCADSA randomized controlled
trial.
|
Level 1
|
Consistent use of CPAP for > 4 hours per night is associated with a lower incidence
of adverse CV outcomes in individuals with CAD and undiagnosed OSA.
|
244 patients
|
|
A meta-analysis of continuous positive airway pressure therapy in prevention of cardiovascular
events in patients with obstructive sleep apnoea.
|
Level 2
|
Revealed a potential trend favoring CPAP therapy in reducing major adverse CV events
in OSA patients when compliance time was adjusted and certain studies were excluded.
|
4,268 patients
|
|
CPAP adherence reduces cardiovascular risk among older adults with obstructive sleep
apnea.
|
Level 2
|
Adherence to the CPAP treatment significantly reduced the risk of new CV events, highlighting
the potential benefits of consistent CPAP therapy in the elderly population.
|
5,024 patients
|
Abbreviations: CAD, coronary artery disease; CPAP continuous positive airway pressure;
CV, cardiovascular; OSA, obstructive sleep apnea.
Bibliographical Record
Kiran Abraham-Aggarwal, Ashutosh Kacker. Is CPAP the Key to Reduce the Cardiovascular
Risk in Patients with OSA?. Int Arch Otorhinolaryngol 2025; 29: s00451801855.
DOI: 10.1055/s-0045-1801855
