Pulmonary hypertension in patients with obstructive sleep apnea: Correlation with disease severity and quality of life

Abstract

BACKGROUND

Obstructive sleep apnea (OSA) is increasingly recognized as a contributor to cardiovascular morbidity, including pulmonary hypertension (PH).

AIM

To assess the prevalence and severity of PH in newly diagnosed OSA patients and evaluate its association with disease severity and quality of life (QoL).

METHODS

In this cross-sectional study, 113 patients newly diagnosed with OSA underwent echocardiography to assess pulmonary artery pressures and completed the World Health Organisation Quality of Life Brief Version (WHOQOL-BREF) questionnaire. OSA severity was determined via polysomnography using the apnea-hypopnea index (AHI). Statistical correlations between AHI, right ventricular systolic pressure (RVSP), mean pulmonary artery pressure (MPAP), and QoL domains were analyzed.

RESULTS

PH (defined by MPAP ≥ 20 mmHg) was observed in 71.68% of patients (MPAP ≥ 20 mmHg). Its prevalence increased with age and OSA severity (P < 0.01). The mean RVSP (39.4 mmHg in males vs 34.1 mmHg in females) and MPAP (27.76 mmHg in males vs 24.64 mmHg in females) values were slightly higher in males but the difference was not statistically significant. AHI and oxygen desaturation index positively correlated with RVSP (r = 0.677) and MPAP (r = 0.543). The WHOQOL-BREF scores were significantly lower in PH patients, particularly in physical and psychological domains (P < 0.01).

CONCLUSION

PH in OSA is strongly linked to disease severity, impairs right ventricular function, and reduces QoL. Findings are limited by the cross-sectional design and reliance on echocardiography instead of right heart catheterization.

Key Words: Apnea-hypopnea index; Obstructive sleep apnea; Pulmonary hypertension; Quality of life; World Health Organization Quality of Life Brief Version

Core Tip: Obstructive sleep apnea (OSA) is increasingly recognized as a contributor to cardiovascular morbidity, including pulmonary hypertension (PH). This present cross-sectional study aimed to assess the prevalence and severity of PH in newly diagnosed OSA patients. Furthermore, it assessed its association with disease severity and quality of life (QoL). PH is a prevalent and underdiagnosed complication of OSA that negatively impacts QoL. There is an imminent need for integration of echocardiographic screening and QoL assessments into the routine management of OSA.

INTRODUCTION

Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder characterized by repetitive episodes of upper airway obstruction during sleep, leading to intermittent hypoxia, sleep fragmentation, and sympathetic overactivity. The standard diagnostic criterion for OSA is an apnea-hypopnea index (AHI) of ≥ 5 events per hour, with obstructive or mixed events accounting for more than 50% of the total respiratory events. When OSA is associated with symptoms such as excessive daytime sleepiness, unrefreshing sleep, or fatigue, it is referred to as OSA syndrome. The prevalence of OSA varies significantly based on population characteristics, with studies estimating its occurrence in approximately 9%-38% of the general adult population, with higher rates in males, individuals with obesity, and the elderly[1].

The pathophysiology of OSA involves a complex interplay of anatomical and neuromuscular factors that contribute to airway collapsibility. Structural abnormalities, such as increased fat deposition in the upper airway, enlarged tonsils, or craniofacial anomalies, can predispose individuals to airway obstruction during sleep. Additionally, impaired neuromuscular control of the pharyngeal dilator muscles, particularly the genioglossus, further exacerbates airway collapse. Recurrent episodes of apnea and hypopnea result in cyclic hypoxia and reoxygenation, triggering oxidative stress, systemic inflammation, and endothelial dysfunction. These pathophysiological changes contribute to an increased risk of developing cardiometabolic disorders, including hypertension, insulin resistance, type 2 diabetes mellitus (T2DM), and cardiovascular disease.

Apnea is defined as a cessation of airflow lasting at least 10 seconds, accompanied by a ≥ 90% reduction in respiratory signal, as measured using an oronasal thermistor or a positive airway pressure device. If inspiratory effort persists during apnea, it is classified as obstructive apnea; if absent throughout, it is central apnea; and if initially absent but later resumes, it is mixed apnea. Hypopnea, a milder form of respiratory disturbance, is characterized by a ≥ 30% reduction in airflow lasting ≥ 10 seconds, accompanied by either a ≥ 3% decrease in oxygen saturation or an arousal from sleep. The presence of respiratory effort-related arousals, which involve progressive respiratory effort leading to sleep disruption without meeting apnea or hypopnea criteria, further contributes to the pathophysiology of OSA[2].

The International Classification of Sleep Disorders, 3^rd edition, outlines diagnostic criteria for OSA, requiring either symptoms of excessive sleepiness, choking during sleep, or witnessed apneic episodes, along with polysomnographic evidence of at least five obstructive respiratory events per hour. In the absence of overt symptoms, a diagnosis can still be made if polysomnography (PSG) reveals 15 or more events per hour[3]. OSA is classified based on AHI into mild (5-15 events/hour), moderate (15-30 events/hour), and severe (> 30 events/hour), with increasing severity correlating with greater cardiovascular and metabolic risks[4].

One of the major complications of OSA is the development of pulmonary hypertension (PH), primarily through hypoxia-induced pulmonary vasoconstriction. Hypoxia leads to serotonin-dependent vascular remodelling, activation of endothelin-1-mediated vasoconstriction, and inhibition of endothelial nitric oxide synthase, impairing vasodilation and increasing pulmonary vascular resistance. Additionally, OSA contributes to left-sided heart failure, which can lead to passive pulmonary congestion and postcapillary PH. Obesity, a common comorbidity in OSA, exacerbates these effects through metabolic dysregulation and chronic vascular inflammation. Decreased levels of adiponectin, an anti-inflammatory and vasculoprotective hormone, further contribute to vascular dysfunction in both OSA and obesity-related PH[5].

Recognizing this clinical gap, the present study was undertaken with the following aims: (1) To estimate the prevalence and severity of PH in newly diagnosed OSA patients; (2) To explore the correlation between PH severity and disease severity as defined by the AHI; and (3) To evaluate the impact of PH on quality of life (QoL) using the World Health Organisation Quality of Life (WHOQOL) Brief Version (WHOQOL-BREF) questionnaire. Additionally, this study aimed to investigate demographic variations in PH burden, specifically in relation to age and gender. By combining clinical, echocardiographic, polysomnographic, and psychosocial data, this study offers a holistic view of a frequently neglected but clinically significant OSA complication—PH. The present study, conducted at a tertiary care teaching hospital in North India, is among the pioneering efforts from this region. In a nutshell, we aim to study the prevalence of PH in patients with OSA and its correlation with disease severity and QoL.

MATERIALS AND METHODS

Study design and setting

This was a cross-sectional single-centre study conducted at the Department of Respiratory Medicine and Department of Cardiology King George’s Medical University. The research was conducted in 2024 over a 12-month period.

Study population

Participants were recruited from the outpatient and inpatient services of the Department of Respiratory Medicine, King George’s Medical University. Patients suspected of having OSA underwent overnight PSG. Those diagnosed with OSA were subsequently evaluated for PH and included in the study based on the eligibility criteria.

Inclusion criteria: The study included adult patients above 18 years of age who provided written informed consent. Eligible participants were those presenting with symptoms of OSA without coexisting chronic obstructive pulmonary disease (COPD), as well as patients with PH secondary to OSA and those newly diagnosed with OSA. Individuals with a body mass index (BMI) greater than 30 kg/m², accompanied by symptoms of OSA, or those with a BMI exceeding 35 kg/m², even in the absence of symptoms, were also enrolled. Additionally, patients at risk of developing hypertension, cardiovascular disease, diabetes mellitus, or thyroid disorders were considered eligible for participation in the study.

Exclusion criteria: Patients were excluded if they failed to provide informed consent or were below 18 years of age. Individuals with active tuberculosis, acute heart failure, pulmonary embolism, or congenital heart disease were not considered eligible. Pregnant women and patients already receiving treatment for OSA were excluded. Similarly, individuals with chronic pulmonary conditions other than COPD, neuromuscular disorders, or central sleep apnea were excluded. In addition, patients with a history of drug abuse or alcoholism were excluded from the study.

Sample size calculation

All consecutive patients presenting to the Department of Respiratory Medicine, King George’s Medical University, who met the inclusion criteria, were enrolled in the study. The minimum sample size was calculated to be 113 participants, based on the reported prevalence of PH among OSA patients of 25% as per Yan et al[6] in 2021. The calculation used a precision of 8% with a 95% confidence interval (95%CI). The formula applied was: n = Z²PQ/d², where n is the required sample size, Z is the Z statistic corresponding to a 95%CI (1.96), P is the estimated prevalence of PH in OSA (0.25), Q is 1 - P (0.75), and d is the desired precision (0.08). Substituting these values yielded a sample size of 113 participants.

Data collection tools and procedures

Each patient enrolled in the study underwent a comprehensive clinical evaluation. Baseline demographic information, such as age, gender, BMI, smoking status, and relevant medical history, was recorded. Particular attention was given to symptoms suggestive of OSA, including excessive daytime sleepiness, persistent fatigue, loud snoring, witnessed episodes of breathing pauses during sleep, frequent awakenings, disturbed sleep, and nocturia. Cardiovascular risk profiling was also conducted, assessing blood pressure, heart rate, and a history of hypertension, diabetes, or metabolic syndrome. To support clinical findings, all suspected cases of OSA were subjected to biochemical investigations, which included fasting thyroid function tests, fasting lipid profile, fasting and postprandial blood glucose, glycated hemoglobin (HbA1c), complete blood count, liver and kidney function tests, human immunodeficiency virus, pro brain natriuretic peptide, and troponin T levels. Following this, patients proceeded to PSG for definitive OSA evaluation.

PSG was performed in accordance with the American Academy of Sleep Medicine guidelines. The diagnosis of OSA was based on the AHI, with classification as normal (< 5 events/hour), mild (5-15 events/hour), moderate (> 15 to 30 events/hour), and severe (> 30 events/hour). The AHI was calculated by dividing the total number of apnea and hypopnea episodes by the number of hours slept, ensuring a standardized measurement of disease severity. The scoring of PSG was automated.

Patients with confirmed OSA were further evaluated for PH using Doppler echocardiography. Pulmonary artery systolic pressure was estimated, and PH was graded as mild [mean pulmonary artery pressure (MPAP) 20-40 mmHg], moderate (41-55 mmHg), or severe (> 55 mmHg). In addition, right ventricular systolic pressure (RVSP) was derived using the Bernoulli equation, incorporating peak tricuspid regurgitation velocity and central venous pressure, to provide a more detailed assessment of right heart function. The sonographer was blinded to OSA severity.

QoL was assessed using the WHOQOL-BREF questionnaire, a globally validated tool designed by the World Health Organization. This instrument includes 26 items covering four domains—physical health, psychological health, social relationships, and environmental health—along with two general questions on overall QoL and health satisfaction. Domain scores range from 4 to 20 and are later transformed to a 0-100 scale, with higher scores reflecting better QoL. Standardized WHO scoring guidelines were used for interpretation, allowing reliable comparison across participants. These results were then analyzed to understand how OSA and associated PH influenced patients’ daily functioning, psychological well-being, and social engagement. A pre-validated Hindi version of the tool was used.

Statistical analysis

Data entry and statistical analysis were performed using SPSS version 25 (IBM Corp., Armonk, NY, United States). Continuous variables were expressed as mean ± SD and categorical variables as n (%). Comparisons between groups (e.g., PH vs non-PH; mild, moderate, severe OSA) were done using: Independent samples t-test and One-way ANOVA with Tukey’s post hoc test. Correlation between PH parameters and AHI, WHOQOL-BREF scores was assessed using Pearson’s correlation coefficient (r). A P value < 0.05 was considered statistically significant.

Data quality assurance

Data were collected using a structured proforma including basic demographic details, relevant past history of patient, spirometry, biochemical examinations, 2D echo and PSG tests. Each participant's data was cross-verified with sleep study and echocardiographic reports. A master sheet was prepared to ensure completeness before final analysis

RESULTS

Study population characteristics

A total of 113 patients newly diagnosed with OSA were included in the study. The mean age of participants was 49.3 ± 12.6 years, with a male predominance (male: female = 1.9:1). The mean BMI was 28.4 ± 3.9 kg/m². About 80% of the participants had hypertension, 54% had T2DM and all participants reported snoring.

Based on MPAP, 71.68% of patients exhibited PH, defined as MPAP ≥ 20 mmHg. Out of total 113 participants, 68 had mild PH (20-40 mmHg), 9 had moderate PH (41-55 mmHg), and 4 had severe PH (> 55 mmHg; Table 1).

Table 1 Pulmonary hypertension prevalence and severity.

OSA	Absent	Mild	Moderate	Severe	Grand total
Mild	23	7	0	0	30
Moderate	5	8	1	0	14
Severe	4	53	8	4	69
Grand total	32	68	9	4	113

χ² = 53.447 with 6 degrees of freedom; P = 0.000. OSA: Obstructive sleep apnea.

OSA severity distribution

Based on the AHI: (1) Mild OSA (AHI 5-14): 26.54%; (2) Moderate OSA (AHI 15-29): 12.38%; (3) Severe OSA (AHI ≥ 30): 61.06%; and (4) A higher proportion of patients with severe OSA exhibited PH (P < 0.01).

Age and gender correlations

Tukey’s HSD post hoc test revealed no significant differences in RVSP across the three age groups (≤ 40 years, 41-60 years, and ≥ 61 years). Mean RVSP differences were small (+2.53, +6.09, and +3.56 mmHg; all P > 0.05), with confidence intervals spanning zero. Homogeneous subset analysis also placed all groups—≥ 61 years (34.68 mmHg), 41-60 years (38.24 mmHg), and ≤ 40 years (40.77 mmHg)—into a single subset (P = 0.445), confirming statistical similarity. These findings demonstrate that age had no significant influence on RVSP among OSA patients. Tukey’s HSD post hoc test following one-way ANOVA showed no significant differences in MPAP across age groups (≤ 40 years, 41-60 years, and ≥ 61 years). Mean differences were small (+0.64, +1.97, and +1.33 mmHg), all with P > 0.05, confirming that age was not a determinant of MPAP in OSA patients. For RVSP, the mean difference between males and females was +5.31 mmHg, but the difference was not statistically significant (P = 0.192). For MPAP, males had a slightly higher mean by +3.12 mmHg, yet this difference also lacked statistical significance (P = 0.225; Tables 2 and 3).

Table 2 Stratification of pulmonary hemodynamic parameters on echocardiography by gender.

Parameter	Gender	n	Mean	SD	SE
RVSP (mmHg)	Male	82	39.4	19.449	2.148
	Female	31	34.1	18.474	3.318
MPAP (mmHg)	Male	82	27.766	12.1859	1.3457
	Female	31	24.642	12.0247	2.1597
TAPSE (mm)	Male	82	21.41	3.489	0.385
	Female	31	21.35	3.469	0.623
TR VEL (m/s)	Male	82	2.5938	0.95492	0.10545
	Female	31	2.2439	0.94023	0.16887

RVSP: Right ventricular systolic pressure; MPAP: Mean pulmonary artery pressure; TAPSE: Tricuspid annular plane systolic excursion; TR VEL: Tricuspid regurgitation velocity.

Table 3 Comparison of right ventricular systolic pressure across age groups.

Age group (year)	n	Mean	SD	SE
≤ 40	22	40.77	21.213	4.523
41-60	66	38.24	19.551	2.407
≥ 61	25	34.68	16.792	3.358
Total	113	37.95	19.252	1.811

Pulmonary hemodynamics and OSA severity

A statistically significant positive correlation was observed between: (1) AHI and RVSP (r = 0.677, P < 0.001); (2) AHI and MPAP (r = 0.695, P < 0.01); and (3) Oxygen desaturation index (ODI) and RVSP (r = 0.543, P < 0.001). These findings suggest a dose-dependent relationship between OSA severity and pulmonary artery pressure elevation (Table 4).

Table 4 Correlation between pulmonary hypertension parameters and obstructive sleep apnea severity indices.

Variable	Correlated parameter	r value1	P value	Direction
RVSP	AHI	0.677	< 0.001	Positive
	ODI	0.543	< 0.001	Positive
	Min SpO2	-0.423	< 0.001	Negative
MPAP	AHI	0.695	< 0.001	Positive
	ODI	0.559	< 0.001	Positive
	Min SpO2	-0.424	< 0.001	Negative
TAPSE	AHI	-0.565	< 0.001	Negative
	ODI	-0.498	< 0.001	Negative
	Min SpO2	0.432	< 0.001	Positive

¹Pearson’s correlation coefficient.

RVSP: Right ventricular systolic pressure; MPAP: Mean pulmonary artery pressure; TAPSE: Tricuspid annular plane systolic excursion; AHI: Apnea-hypopnea index; ODI: Oxygen desaturation index; MinSpO₂: Minimum oxygen saturation.

QoL (WHOQOL-BREF) outcomes

RVSP demonstrated significant negative correlations with three of the four WHOQOL domains. Specifically, higher RVSP values were associated with lower physical health scores (r = -0.407, P < 0.001), indicating that patients with elevated pulmonary pressures tended to report worse physical functioning.

MPAP showed a consistent and stronger negative relationship with the same three domains. There was a statistically significant inverse correlation with physical health (r = -0.471, P < 0.001), psychological status (r = -0.384, P < 0.001), and social relationships (r = -0.431, P < 0.001), indicating that increased pulmonary arterial pressure had a more profound and pervasive effect on perceived QoL. Interestingly, MPAP was also significantly negatively correlated with domain 4: Environment (r = -0.271, P = 0.004), which was not seen with RVSP. This might be due to the fact that MPAP reflects the overall pulmonary vascular load and is a stable marker of disease severity, whereas RVSP measures only systolic pressure and is prone to variability. Since environmental QoL limitations relate more to chronic hemodynamic burden than to peak systolic load, only MPAP showed a significant negative correlation (Table 5).

Table 5 Correlation between pulmonary hemodynamic parameters on echocardiography and World Health Organisation Quality of Life Brief Version domains.

Variable	Domain (WHOQOL-BREF)	r value1	P value	Direction
RVSP	Physical health	-0.407	< 0.001	Negative
	Psychological	-0.325	< 0.001	Negative
	Social relationships	-0.387	< 0.001	Negative
MPAP	Physical health	-0.471	< 0.001	Negative
	Psychological	-0.384	< 0.001	Negative
	Social relationships	-0.431	< 0.001	Negative
	Environment	-0.271	0.004	Negative
TAPSE	Physical health	0.379	< 0.001	Positive
	Psychological	0.298	0.001	Positive
	Social relationships	0.427	< 0.001	Positive

¹Pearson’s correlation coefficient.

RVSP: Right ventricular systolic pressure; MPAP: Mean pulmonary artery pressure; TAPSE: Tricuspid annular plane systolic excursion; WHOQOL-BREF- World Health Organisation Quality of life Brief Version.

DISCUSSION

This cross-sectional study of 113 newly diagnosed OSA patients demonstrated a high prevalence of PH and highlighted its strong association with disease severity rather than demographic factors. The cohort was predominantly middle-aged with a clear male predominance (72.6%). This pattern is consistent with previous studies, including Sharma et al[7] who reported a similar male predominance in Indian OSA populations. The protective effects of estrogen and progesterone in premenopausal women, as discussed in earlier literature, may partly explain the lower prevalence among females.

In our study, lifestyle risk factors such as smoking (14.2%) and alcohol use (3.5%) were relatively uncommon, yet PH and OSA were prevalent, suggesting that metabolic factors and obesity were stronger drivers of disease. Dubey et al[8] similarly reported that smoking was not independently associated with OSA severity after adjusting for BMI and neck circumference. Simou et al[9], however, found in their meta-analysis that heavy alcohol intake increased OSA risk by 25%. The low alcohol prevalence in our cohort, therefore, points to obesity and metabolic comorbidities as more dominant contributors.

Comorbid conditions were highly prevalent, with hypertension affecting 80.5% and T2DM affecting 53.1% of patients. This aligns with the pathophysiological interplay between OSA, sympathetic activation, and metabolic dysregulation. Peppard et al[10] demonstrated a dose-dependent increase in hypertension risk with increasing OSA severity, while Reutrakul et al[11] reported significant associations between OSA and higher HbA1c levels. Our findings reinforce this bidirectional relationship, as poor glycemic control and dyslipidemia were prominent in the study population.

PH was detected in 71.7% of patients, with mild PH being the most common presentation. Echocardiographic evidence of right atrial and right ventricular enlargement was seen in 31.9% of patients, indicating early structural cardiac remodeling. Vitarelli et al[12] reported similar findings of right ventricular dilation in untreated OSA patients, with severity correlating with nocturnal desaturation.

When analyzed by age, RVSP and MPAP did not show significant differences, with P values of 0.550 and 0.848, respectively. Although younger patients had slightly higher RVSP, age was not a determinant of PH. Sanner et al[13] also observed that mild PH could develop in OSA patients irrespective of age, with severity and hypoxemia being more important drivers. Similarly, Kessler et al[14] reported that PH in OSA was more closely related to daytime hypoxemia and coexisting COPD than chronological age, consistent with our findings.

Gender-based comparisons showed that males had slightly higher RVSP and MPAP than females, though differences were not statistically significant. Nonetheless, the trend reflects earlier reports by Lin et al[15] who found that men exhibited greater pulmonary artery pressures and right ventricular wall thickness than women despite comparable AHI values. This suggests a possible gender predisposition to cardiovascular consequences of OSA, though our study did not demonstrate significant differences.

RVSP and MPAP correlated strongly with AHI (r = 0.677 and 0.695, respectively), ODI, and minimum SpO₂, emphasizing a dose-dependent effect of nocturnal respiratory disturbances on pulmonary vasculature. Tricuspid annular plane systolic excursion showed negative correlations with AHI (r = -0.565) and ODI (r = -0.498), reflecting declining right ventricular function with increasing OSA severity. These findings were strongly supported by those of Sanner et al[13], who demonstrated that patients with moderate-to-severe OSA exhibited elevated pulmonary artery pressures even in the absence of overt lung disease. Their work confirmed that OSA severity—particularly nocturnal hypoxemia—was an independent predictor of mild PH, aligning well with the correlations observed in the current study.

QoL outcomes provided further evidence of the systemic burden of OSA with PH. Both RVSP and MPAP were inversely associated with physical, psychological, and social domains of the WHOQOL-BREF. Notably, MPAP also showed a weak but significant negative correlation with the environmental domain, suggesting a broader impact of elevated pulmonary pressures. Minai et al[16] similarly reported that patients with OSA and concurrent PH experienced significantly worse health-related QoL scores compared to those with OSA alone.

Limitations of the study

This study has certain limitations that should be acknowledged. Being cross-sectional in design, it cannot establish a causal relationship between OSA severity and PH. Pulmonary pressures were assessed using echocardiography rather than right heart catheterization, which remains the gold standard. Finally, QoL was evaluated using the WHOQOL-BREF, a generic tool, instead of an OSA-specific instrument, which may have limited sensitivity in capturing disease-specific impairments.

Future directions

Future research should adopt longitudinal designs to clarify causal links between OSA and PH. Use of right heart catheterization and OSA-specific QoL tools would provide more precise insights. Larger, multicenter studies and interventional trials assessing therapies such as CPAP and weight reduction are needed to confirm whether improving OSA control can reduce pulmonary pressures and enhance patient well-being.

CONCLUSION

This study highlighted that PH is highly prevalent among patients with OSA and is strongly linked to disease severity rather than age or sex. Echocardiographic evidence of elevated pulmonary pressures and right heart changes correlated closely with AHI, oxygen desaturation, and reduced right ventricular function. Importantly, these hemodynamic alterations were associated with poorer QoL scores, particularly in physical, psychological, and social domains. The findings emphasize the need for early recognition, comprehensive evaluation, and timely management of OSA to mitigate cardiopulmonary complications and improve patient well-being.