The Clinical Characteristics of Patients With Pulmonary Hypertension Combined With Obstructive Sleep Apnoea

Lu Yan; Zhihui Zhao; Qing Zhao; Qi Jin; Yi Zhang; Xin Li; Anqi Duan; Qin Luo; Zhihong Liu


BMC Pulm Med. 2021;21(378) 

In This Article

Study Methods

This single-centre observational study was conducted at Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences. The study was conducted with the approval of the Ethics Committee of Fuwai Hospital. Written informed consent was obtained from all the participants.

Study Sample

All enrolled patients underwent respiratory polygraphy and presented a stable clinical state. Respiratory polygraphy examinations were performed before or after RHC at intervals not exceeding 7 days. Data were collected from consecutive hospitalized patients diagnosed with PH by RHC between December 2018 and December 2020. Patients whose RHC results showed a mean pulmonary arterial pressure (mPAP) of ≥ 25 mmHg were diagnosed with PH. Based on the respiratory polygraphy results, the participants were divided into two groups: PH patients without OSA and PH patients with OSA. The exclusion criteria were as follows: (1) patients who were not diagnosed with PH; (2) patients aged < 18 years or > 75 years; (3) patients with chronic liver or renal insufficiency, defined as a liver enzyme more than 3 times the normal value and a creatinine clearance rate < 30 ml/min; (4) patients with life-threatening arrhythmia; (5) patients with nightly sleep time less than two hours; (6) patients with BMI ≥ 35 kg/m2; and (7) patients with a previous diagnosis of sleep-disordered breathing (see Figure 1).

Figure 1.

Flow chart of patient inclusion and exclusion. RHC, right heart catheterization; liver and kidney insufficiency, defined as a liver enzyme more than 3 times the normal value and a creatinine clearance rate < 30 ml/min; BMI, body mass index; mPAP, mean pulmonary artery pressure

Patient Assessment

The baseline clinical characteristics of each subject, including age, sex, BMI, smoking history, six-minute walk distance (6MWD), World Health Organization functional class (WHO FC), comorbidities, and medication history, were collected separately. In addition, fasting venous blood was collected on admission to evaluate N-terminal pro-brain natriuretic peptide (NT-proBNP), C-reactive protein (CRP) and high-sensitivity C-reactive protein (hs-CRP) levels. Oxygen partial pressure (PaO2), carbon dioxide partial pressure (PaCO2), and peripheral capillary oxygen saturation (SpO2) were determined by arterial blood gas tests. All patients completed the Epworth Sleepiness Scale (ESS)[14] before undergoing sleep breathing monitoring. Echocardiography and pulmonary function testing were performed on each patient before RHC. All subjects underwent RHC to obtain their baseline haemodynamic parameters, i.e., mean right atrial pressure (mRAP), mPAP, cardiac index (CI), and pulmonary vascular resistance (PVR).

Cardiorespiratory Study

Each enrolled PH patient underwent overnight cardiorespiratory recording using an Embletta system (Medcare Flaga, Reykjavik, Iceland) at the sleep centre of Fuwai Hospital. The device recorded nasal airflow, finger pulse oximetry, thoracoabdominal movements, body position, and snoring. According to the American Academy of Sleep Medicine (AASM) Manual for Scoring Sleep and Related Events, sleep apnoea is defined as a complete cessation of oronasal respiratory airflow during sleep or a decrease of more than 90% from baseline, either one lasting for more than 10 s. Hypopnoea is defined as a decrease in respiratory airflow intensity during sleep of more than 30% from baseline, accompanied by a decrease in oxygen saturation ≥ 3% from baseline. If the apnoea-hypopnoea index (AHI) was ≥ 5/h, sleep apnoea was diagnosed. If the apnoea event was accompanied by the cessation of respiratory movement in the chest and abdomen, it was considered a central apnoea event; otherwise, it was considered an obstructive event. OSA was diagnosed if obstructive AHI totalled ≥ 5/h and the obstructive events accounted for > 50% of the apnoeic events. In our study, there were 35 patients diagnosed with OSA among the 140 PH patients. The incidence of OSA was 76%, 50%, 15.4%, 11.8%, and 8% in patients with PH associated with pulmonary disease or low oxygen, CTEPH, CTD-PAH, others, and CHD-PAH, respectively.

Cardiopulmonary Exercise Test

All consecutively enrolled patients with newly diagnosed IPAH underwent cardiopulmonary exercise testing (CPET) (Cosmed S.R.L., Rome, Italy). The operational criteria for the cardiopulmonary exercise test were as follows: 3 min of rest, then 3 min of idling, followed by increments of 5–20 W (depending on the patient's exercise capacity) until the patient reached a symptom-limited maximal exercise state. Peak oxygen uptake (peak VO2) was defined as the maximal oxygen uptake over a 30-s period at maximal exertion during the continuous incremental power test. Minute ventilation/carbon dioxide output at the anaerobic threshold (VE/VCO2) was defined as the ratio of required ventilation (VE) per 1 L of CO2 expelled at the anaerobic threshold.

Statistical Analysis

The continuous variables are presented as means ± standard deviations or percentages, and the categorical variables are presented as counts or percentages. For the continuous variables, the means of two independent samples conforming to a normal distribution were compared by the two-independent-samples t-test, and categorical variables were compared by the chi square test. A P-value < 0.05 was considered significant. A logistic regression analysis was also used to explore the factors associated with prolonged OSA in PH patients. All data were analysed by SPSS 22.0 software.

Basic Characteristics of Patients Included in This Study

A total of 164 patients were newly diagnosed with PH and presented a stable clinical status. At the time of this study, they were in stable condition and had been on the same therapy for at least 1 month. Among them, 150 patients underwent overnight cardiorespiratory monitoring before or after RHC. Finally, a total of 140 patients with complete sleep data were enrolled. The baseline clinical characteristics of all PH patients with and without OSA were compared, as shown in Table 1; the average age of the 140 patients was 39.5 ± 13.55 years, and 76.4% (107/140) were female. The average BMI was 23.17 ± 3.86 kg/m2. The average heart rate was 83.42 ± 13.82/min, the average systolic pressure was 113.17 ± 13.94 mmHg, and the average diastolic pressure was 73.4 ± 11.45 mmHg. The mPAP in the static state was 55.73 ± 17.06 mmHg and the average NT-proBNP was 1260.35 ± 1364.62 pg/ml. There were 35 patients diagnosed with OSA among the 140 PH patients. The incidence of OSA was 76%, 50%, 15.4%, 11.8%, and 8% in patients with PH associated with pulmonary disease or low oxygen, CTEPH, CTD-PAH, others, and CHD-PAH, respectively (see Table 1 and Table 2).

The Comparison of Sleep Breathing Monitoring Indicators in Patients With and Without OSA

The AHI boundary value was 5, and 35 (25%) patients had OSA out of the 140 patients with high pulmonary pressure. The AHI in patients with OSA was 16.18 ± 12.65 versus 1.62 ± 1.21 in those without (P < 0.001), and the average oxygen saturation was 88.89 ± 4.86 versus 91.90 ± 4.68 (P = 0.439). The nocturnal minimum oxygen saturation was 75.8 ± 11.55 versus 83.52 ± 7.13 (P = 0.002) (See Table 3).

The Comparison of Routine Clinical Examination Values in Patients With and Without OSA

PH patients with OSA were older (46.74 ± 14.25 years vs. 37.06 ± 12.46, P = 0.001) and had a higher proportion of males (57.1% vs. 82.9%, P = 0.001) than PH patients without OSA. SBP and DBP were higher in patients with OSA (118.86 ± 14.71 mmHg vs. 111.28 ± 13.22 mmHg, P = 0.004 and 76.83 ± 14.79 mmHg vs. 72.26 ± 9.92 mmHg, P = 0.006, respectively). PaO2 was lower (63.69 ± 10.21 mmHg vs. 71.77 ± 15.21 mmHg, P = 0.014) in patients with OSA than patients without OSA. mPAP was also lower (53.57 ± 13.08 mmHg vs. 56.45 ± 18.19 mmHg, P = 0.01) in patients with OSA. The laboratory and haemodynamic characteristics did not differ between the two groups. Echocardiographic and cardiopulmonary exercise test parameters also did not differ between the two groups (see Table 4).

Logistic Regression Analysis Corrected for BMI to Indicate OSA

Through multivariate logistic regression analysis corrected for BMI, we found that age (OR 1.039, 95% CI 1.005–1.975, P = 0.025), sex/female sex (OR 0.288, 95% CI 0.112–0.738, P = 0.01), SBP (OR 1.03, 95% CI 0.998–1.064, P = 0.068), and PaO2 (OR 0.965, 95% CI 0.931–1, P = 0.049) were associated with OSA in PH patients. Higher age, male sex, and lower daytime PaO2 had the strongest ability to indicate OSA in PH patients (see Table 5).