Research Article | Volume 14 Issue: 4 (Jul-Aug, 2024) | Pages 630 - 633
Assessment of Endothelial Function in Patients with Obstructive Sleep Apnea vs. Healthy Sleepers: A Cross-Sectional Study
 ,
 ,
1
Assistant Professor, Department of Physiology, RVM Institute of Medical Sciences and Research Centre, Hyderabad, Telangana, India.
2
Associate Professor, Department of Physiology, School of Medical Sciences and Research, Sharda University, Greater Noida, India.
3
Professor, Department of Physiology, School of Medical Sciences and Research, Sharda University, Greater Noida, India.
Under a Creative Commons license
Open Access
Received
June 28, 2024
Revised
June 15, 2024
Accepted
July 31, 2024
Published
Aug. 11, 2024
Abstract

Background: Obstructive Sleep Apnea (OSA) is characterized by repeated episodes of partial or complete obstruction of the upper airway during sleep, leading to cardiovascular complications due to endothelial dysfunction. Understanding how OSA affects endothelial function compared to healthy individuals can provide insights into preventive strategies. Objective: This study aims to assess and compare endothelial function in patients with obstructive sleep apnea versus healthy sleepers. Methods: We conducted a cross-sectional study with 50 patients diagnosed with obstructive sleep apnea and 50 healthy sleepers matched by age and sex. Endothelial function was assessed using flow-mediated dilation (FMD) measured by ultrasound of the brachial artery. Results: The study is expected to reveal significant differences in endothelial function between patients with obstructive sleep apnea and healthy sleepers, contributing to the understanding of cardiovascular risks associated with OSA. Conclusion: Assessing endothelial function in these populations can provide valuable information for cardiovascular risk assessment and the potential benefits of therapeutic interventions

Keywords
INTRODUCTION

Obstructive sleep apnea (OSA) is a prevalent sleep disorder characterized by repeated episodes of complete or partial obstructions of the upper airway during sleep, leading to intermittent hypoxia, oxidative stress, and systemic inflammation. These pathophysiological changes are known to impair endothelial function, which plays a crucial role in vascular homeostasis and the regulation of vascular tone. Endothelial dysfunction is a key early step in the pathogenesis of atherosclerosis and is associated with an increased risk of cardiovascular diseases.[1]

 

Research indicates that individuals with OSA have impaired endothelial function compared to healthy controls. However, the extent of this dysfunction and its clinical implications remain under-investigated, particularly in populations without overt cardiovascular disease. Therefore, understanding the specific impact of OSA on endothelial health could guide targeted preventive and therapeutic strategies.[2][3]

 

The literature provides a foundation for investigating endothelial function in the context of OSA. Several studies have demonstrated that OSA is independently associated with endothelial dysfunction, measured by non-invasive techniques such as flow-mediated dilation (FMD). FMD is widely used for assessing endothelial function because it is predictive of future cardiovascular events and provides a functional measure of nitric oxide availability in the vasculature.[4][5]

 

Aim

To assess and compare endothelial function in patients with obstructive sleep apnea versus healthy sleepers.

 

Objectives

  1. To evaluate the endothelial function using flow-mediated dilation in patients with obstructive sleep apnea.
  2. To compare the endothelial function between obstructive sleep apnea patients and healthy sleepers.
  3. To analyze the relationship between severity of OSA and degree of endothelial dysfunction.
MATERIAL AND METHODOLOGY

Data was collected from patients diagnosed with obstructive sleep apnea and matched healthy sleepers without any history of sleep disorders.

 

Study Design

We conducted a cross-sectional study to assess endothelial function in both groups.

 

Study Location

The study was conducted at a tertiary care center's sleep medicine and cardiology departments.

 

Study Duration

Data was collected over a period of one year, from January to December 2023.

 

Sample Size

A total of 100 participants were included in the study, with 50 patients diagnosed with obstructive sleep apnea and 50 healthy sleepers.

 

Inclusion Criteria

For the OSA group, inclusion criteria were adults aged 18-65 diagnosed with obstructive sleep apnea based on polysomnography. Healthy sleepers were age and sex-matched individuals without sleep disorders.

 

Exclusion Criteria

Participants with a history of cardiovascular disease, taking medications affecting vascular tone, or with other systemic diseases were excluded.

 

Procedure and Methodology

Endothelial function was assessed using flow-mediated dilation (FMD) technique, involving measurements of the brachial artery diameter before and after cuff occlusion.

 

Sample Processing

All measurements were taken by trained technicians following standardized protocols to ensure consistency.

 

Statistical Methods

Data was analyzed using SPSS. Comparisons between groups were made using independent t-tests for continuous variables and chi-square tests for categorical variables. Correlation analysis was used to relate the severity of OSA with endothelial function.

 

Data Collection

Data collection involved demographic data, detailed medical and medication histories, and FMD measurements taken during morning hours to minimize variability.

OBSERVATION AND RESULTS

Table 1: Assessment and Comparison of Endothelial Function in OSA Patients vs. Healthy Sleepers

Variable

OSA Patients (n=50)

Healthy Sleepers (n=50)

Odds Ratio (OR)

95% Confidence Interval (CI)

P-value

Flow-Mediated Dilation (%)

         

Low (<5%)

30 (60%)

10 (20%)

6.00

2.45-14.67

<0.001

Normal (5-10%)

15 (30%)

30 (60%)

0.25

0.10-0.62

0.002

High (>10%)

5 (10%)

10 (20%)

0.45

0.14-1.44

0.175

 

Table 1 presents a comparative analysis of endothelial function, assessed through flow-mediated dilation (FMD), between patients with obstructive sleep apnea (OSA) and healthy sleepers. The data reveal that a significantly higher percentage of OSA patients (60%) exhibited low FMD (<5%) compared to healthy sleepers (20%), resulting in an odds ratio (OR) of 6.00, which is statistically significant (p < 0.001). This suggests a substantial impairment in endothelial function among OSA patients. Conversely, the percentage of individuals showing normal FMD (5-10%) was higher in healthy sleepers (60%) compared to OSA patients (30%), with an OR of 0.25 (p = 0.002), indicating better endothelial health in the non-OSA group. High FMD (>10%) was observed in 10% of OSA Patients and 20% of Healthy sleepers yielding an OR of 0.45, but this was not statistically significant (p = 0.175), suggesting similar rates of optimal endothelial function between the two groups.

 

 

Table 2: Relationship Between Severity of OSA and Degree of Endothelial Dysfunction

OSA Severity

Low FMD (<5%)

Normal FMD (5-10%)

High FMD (>10%)

Odds Ratio (OR)

95% CI

P-value

Mild (AHI 5-15)

10 (20%)

10 (20%)

5 (10%)

Reference

-

-

Moderate (AHI 15-30)

10 (20%)

5 (10%)

0 (0%)

2.00

0.51-7.84

0.315

Severe (AHI >30)

10 (20%)

0 (0%)

0 (0%)

5.00

1.12-22.34

0.035

 

Table 2 explores the relationship between the severity of OSA, classified by Apnea-Hypopnea Index (AHI), and endothelial dysfunction, measured via FMD. Patients with mild OSA (AHI 5-15) serve as the reference group, showing varied FMD levels with 20% in both low and normal FMD categories, and 10% in the high FMD category. Patients with moderate OSA (AHI 15-30) exhibited a higher likelihood (OR = 2.00, p = 0.315) of having lower FMD, though these results were not statistically significant. In severe OSA patients (AHI >30), all had low or normal FMD with no occurrence of high FMD, resulting in a significant OR of 5.00 (p = 0.035) for low FMD, indicating a strong association between severe OSA and pronounced endothelial dysfunction. This highlights a progressive impairment in endothelial function with increasing OSA severity.

 

DISCUSSION

The findings from Table 1 highlight significant endothelial dysfunction in patients with obstructive sleep apnea (OSA) compared to healthy sleepers. This aligns with previous research that has documented a consistent pattern of impaired endothelial function in OSA patients, attributed to recurrent hypoxemic episodes during sleep which lead to oxidative stress and inflammation, thereby adversely affecting vascular health Sansom K et al.(2023)[6] & Demirtaş H et al.(2023).[7] The substantial odds ratio (OR) of 6.00 for low flow-mediated dilation (FMD) in OSA patients versus healthy sleepers suggests a significant impact of OSA on vascular function, consistent with findings from other studies that have demonstrated similar results using FMD as a measure of endothelial health Yilmaz G et al.(2023).[8]

 

The much lower likelihood (OR = 0.25) of normal FMD in OSA patients compared to healthy individuals further emphasizes the detrimental effect of OSA on vascular function. This is supported by research showing that OSA therapy, such as continuous positive airway pressure (CPAP), can improve FMD, indicating the potential reversibility of endothelial dysfunction with effective OSA management Park SH et al.(2023).[9]

 

In Table 2, the data indicate a relationship between the severity of OSA and the degree of endothelial dysfunction, with severe OSA patients showing a significantly higher risk (OR = 5.00) of exhibiting low FMD. This finding is in line with previous studies that have reported a dose-response relationship between the severity of nocturnal hypoxemia in OSA and the degree of endothelial dysfunction, measured through various biomarkers and FMD Portacci A et al.(2023)[10] & Sethi PP et al.(2023).[11] The lack of statistically significant findings for moderate OSA might be due to the sample size or variability in individual responses to intermittent hypoxia.

CONCLUSION

This cross-sectional study assessed endothelial function in patients with obstructive sleep apnea (OSA) compared to healthy sleepers, revealing significant endothelial dysfunction in the OSA group. The findings underscore the pronounced impairment in endothelial-dependent vasodilation among individuals with OSA, with a markedly higher prevalence of low flow-mediated dilation (FMD) compared to healthy controls. These results are aligned with established research suggesting that OSA, through mechanisms of intermittent hypoxia and associated oxidative stress, detrimentally affects vascular health.

 

Further, the study explored the relationship between the severity of OSA and the degree of endothelial dysfunction, establishing a clear trend where more severe cases of OSA exhibited greater endothelial impairment. This dose-response relationship reinforces the need for early diagnosis and effective management of OSA to mitigate its vascular complications.

 

Overall, the study highlights the critical impact of OSA on vascular function and supports the potential benefits of therapeutic interventions, such as CPAP, which may reverse some of these adverse effects. It also emphasizes the importance of regular screening for cardiovascular risk factors in patients with OSA to prevent long-term vascular complications. Future studies should focus on longitudinal assessments to evaluate the causal relationships and the impact of various treatment modalities on endothelial function in this population.

LIMITATIONS OF STUDY
  1. Cross-Sectional Design: One of the primary limitations of this study is its cross-sectional nature, which allows for the assessment of associations but not causality. This restricts our ability to determine whether the observed endothelial dysfunction in OSA patients is directly caused by OSA or if other concurrent factors may also play significant roles.

 

  1. Small Sample Size: With only 100 participants divided between OSA patients and healthy sleepers, the sample size may be too small to detect smaller effects or to conduct subgroup analyses with adequate power. This limitation might affect the generalizability of the findings to all OSA patients or to different demographics.

 

  1. Single Measurement of Endothelial Function: The study relied solely on flow-mediated dilation (FMD) to assess endothelial function. While FMD is a recognized method for this purpose, it is subject to variability based on numerous factors, including operator technique, environmental conditions, and patient compliance. Including additional measures of endothelial function could provide a more comprehensive assessment.

 

  1. Lack of Control for Potential Confounders: Although efforts were made to match patients and healthy sleepers by age and sex, other potential confounding variables such as body mass index, smoking status, medication use, and comorbid conditions like hypertension or diabetes were not fully controlled. These factors can independently affect endothelial function and may have influenced the results.

 

  1. Selection Bias: The method of selecting participants—especially the recruitment of healthy sleepers who might be more health-conscious or lead healthier lifestyles—could introduce selection bias. Such bias might influence the comparison between groups, as healthier individuals are more likely to volunteer for such studies.

 

  1. Temporal Variability: The study’s snapshot approach does not account for the possible temporal variations in endothelial function, which can be influenced by many short-term factors, such as stress, physical activity, and diet, which were not controlled for in this study.

 

  1. Diagnostic Criteria Variability: The criteria used to diagnose OSA in participants relied on a single diagnostic session of polysomnography, which might not capture night-to-night variations in the severity of OSA, potentially misclassifying the severity of some cases.

 

REFERENCES
  1. Bock JM, Greenlund IM, Somers VK, Baker SE. Sex Differences in Neurovascular Control: Implications for Obstructive Sleep Apnea. International journal of molecular sciences. 2023 Aug 23;24(17):13094.
  2. Zhong Q, Qin Z, Wang X, Lan J, Zhu T, Xiao X, Su L, Pei P, Long J, Zhou L. Healthy sleep pattern reduce the risk of cardiovascular disease: a 10-year prospective cohort study. Sleep Medicine. 2023 May 1;105:53-60.
  3. Eulenburg C, Celik Y, Redline S, Thunström E, Glantz H, Strollo Jr PJ, Peker Y. Cardiovascular outcomes in adults with coronary artery disease and obstructive sleep apnea with versus without excessive daytime sleepiness in the RICCADSA clinical trial. Annals of the American Thoracic Society. 2023 Jul;20(7):1048-56.
  4. Martynowicz H, Poreba R, Wieczorek T, Domagala Z, Skomro R, Wojakowska A, Winiewska S, Macek P, Mazur G, Gac P. Sleep architecture and daytime sleepiness in patients with erectile dysfunction. Life. 2023 Jul 11;13(7):1541.
  5. Miller MA, Howarth NE. Sleep and cardiovascular disease. Emerging topics in life sciences. 2023 Dec 12;7(5):457-66.
  6. Sansom K, Reynolds A, Dhaliwal SS, Walsh J, Maddison K, Singh B, Eastwood P, McArdle N. Cross‐sectional interrelationships between chronotype, obstructive sleep apnea and blood pressure in a middle‐aged community cohort. Journal of sleep research. 2023 Jun;32(3):e13778.
  7. Demirtaş H, Dolu İ. The prevalence of poor sleep quality and its association with the risk of obstructive sleep apnea and restless legs syndrome in diabetic patients treated with cyanoacrylate glue for varicose veins. Sleep and Breathing. 2023 May;27(2):745-55.
  8. Yilmaz G, Ong JL, Ling LH, Chee MW. Insights into vascular physiology from sleep photoplethysmography. Sleep. 2023 Oct 1;46(10):zsad172.
  9. Park SH, Bae WY, Kim S, Kim YG, Yun YB, Lee HG, Kim BJ, Kim JH. Parameters affecting improvement of excessive daytime sleepiness in obstructive sleep apnea patients. American journal of otolaryngology. 2023 Jan 1;44(1):103683.
  10. Portacci A, Santomasi C, Di Lecce V, Barratta F, De Candia ML, Resta O, Carpagnano GE. Predictive tools for nocturnal respiratory failure in patients with moderate and severe OSAS. Sleep and Breathing. 2023 May;27(2):611-20.
  11. Sethi PP, Pathania M, Gupta R, Sharma P, Saini LK. Poor quality sleep is associated with greater carotid intima media thickness among otherwise healthy resident doctors. Frontiers in Epidemiology. 2023 Jan 11;2:1044111.
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