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)

Conclusion

OSA has a high incidence in patients with PH. OSA may aggravate PH to some extent, and advanced age, male sex and lower daytime PaO2 could predict the presence of OSA. It may be important to identify and treat PH patients with OSA. The clinical significance of PH with OSA requires further investigation.

Limitation

First, because polysomnography is time-consuming and laborious, it is generally not used for preliminary screening. Therefore, portable cardiopulmonary breathing monitoring was used for patient sleep monitoring in this study. Due to the low incidence of PH, too few patients had each disease type for subgroup analysis, and selection bias was inevitable in this prospective study. In addition, we did not follow up the patients, so we could not determine the effect of OSA on the long-term survival of patients with PH. We did not investigate whether PH could be alleviated by the correction of OSA. Large, prospective cohort studies are needed to further explore these issues.

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Acknowledgements
Not applicable.

Funding
National Natural Science Foundation of China (81370326,81641005), Beijing Municipal Science and Technology Project (Z181100001718200). National Precision Medical Research Program of China (2016YFC0905602).

Availability of data and materials
All relevant raw data, will be freely available to any researcher wishing to use them for non-commercial purposes, without breaching participant confidentiality.

Declarations
Ethics approval and consent to participate
This single-center 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. The study was performed with the approval of Fuwai Hospital Ethics Committee (No.2009215). Written Informed Conferences of all participants were obtained.

Consent for publication
The work described has not been submitted elsewhere for publication, in whole or in part, and all the authors listed have approved the manuscript that is enclosed.

Table 1. Baseline characteristics and 6MWD of all patients
Variable	All patients	IPAH	CTD-PAH	CHD-PAH	Pulmonary disease or low oxygen	CTEPH	unknown mechanisms PH
Number of patients	140	40	13	25	25	20	17
Age (years)	39.5 ± 13.55	30.95 ± 8.91	41.69 ± 11.65	36 ± 14.12	46.28 ± 14.81	48.85 ± 10.27	41.94 ± 12.33
Females (N%)	107 (76.4%)	31 (77.5%)	13 (100%)	21 (84%)	18 (72%)	10 (50%)	12 (71%)
BMI (kg·m⁻²)	23.17 ± 3.86	22.58 ± 3.17	23.62 ± 3.56	20.50 ± 2.88	25.4 ± 4.55	24.76 ± 2.79	23 ± 4.41
SBP (mmHg)	113.17 ± 13.94	110.93 ± 13.03	111.15 ± 18.56	111.4 ± 16.60	115.56 ± 12.91	118 ± 11.22	113.41 ± 12.06
DBP (mmHg)	73.4 ± 11.45	71.95 ± 9.06	73 ± 10.82	72.44 ± 10.34	75.76 ± 9.37	80.55 ± 11.10	66.65 ± 16.88
HR (beats/min)	83.42 ± 13.82	80.6 ± 13.45	82.54 ± 14.12	83.36 ± 14.91	87.2 ± 12.61	86.65 ± 15.56	81.47 ± 12.25
6MWD (m)	405.66 ± 105.08	439.95 ± 104.53	431.11 ± 84.96	435.57 ± 75.19	354.72 ± 87.99	350.11 ± 116.21	404.69 ± 120.54
OSA (N%)	35 (25%)	0 (0%)	2 (15.4%)	2 (8%)	19 (76%)	10 (50%)	2 (11.8%)

Table 2. Baseline blood gas, NT-proBNP, haemodynamics, and CPET examination characteristics of all patients
Variable	All patients	IPAH	CTD-PAH	CHD-PAH	Pulmonary disease or low oxygen	CTEPH	unknown mechanisms PH
Number of patients	140	40	13	25	25	20	17
PaO₂ (mmHg)	69.75 ± 14.52	75.40 ± 13.13	73.64 ± 12.28	65.51 ± 18.38	65.03 ± 11.94	61.22 ± 7.97	77.08 ± 13.85
PaCO₂ (mmHg)	35.93 ± 6.89	35.48 ± 3.42	33.64 ± 3.83	36.68 ± 13.19	38.65 ± 13.19	33.73 ± 3.85	36.05 ± 2.70
SaO₂ (%)	92.88 ± 4.53	94.22 ± 4.76	94.3 ± 2.31	90.95 ± 5.70	91.69 ± 4.43	91.49 ± 3.45	95.09 ± 2.03
NT-proBNP (pg/ml)	1260.35 ± 1364.62	1063.88 ± 1410.25	1527.68 ± 1583.17	1688.02 ± 671.05	1621.12 ± 1188.38	1986.57 ± 1926.25	974.92 ± 769.72
Mean PAP (mmHg)	55.73 ± 17.06	57.55 ± 19.93	50.77 ± 13.52	68.12 ± 20.46	52.76 ± 9.32	48.3 ± 8.9	50.12 ± 13.62
PVR (dyn•s•cm-5)	1128.66 ± 490.40	1214.71 ± 556.99	1032.50 ± 406.93	1077.91 ± 514.50	1298.43 ± 492.18	1008.06 ± 310.30	979.89 ± 477.77
CI (L/min/m²)	2.79 ± 1.35	2.75 ± 0.7	2.84 ± 0.48	3.63 ± 2.36	2.47 ± 0.58	1.35 ± 1.46	3.01 ± 0.85
MRAP (mmHg)	6.01 ± 4.47	5.82 ± 4.23	5.23 ± 6.15	6.6 ± 4.13	6.56 ± 4.65	6.53 ± 4.30	4.77 ± 4.24
PeakVO2/kg (mL/min/kg)	12.65 ± 3.93	13.89 ± 4.32	11.44 ± 2.66	13.87 ± 4.08	10.55 ± 2.34	10.27 ± 2.37	14.19 ± 4.23
VE/VCO2	42.99 ± 9.80	42.35 ± 9.71	39.96 ± 8.80	42.47 ± 8.13	44.9 ± 11.27	47.03 ± 11.91	40.24 ± 7.47

Continuous variables are presented as mean ± SD. Categorical variables are given as counts. IPAH, idiopathic pulmonary arterial hypertension; CTD-PAH, pulmonary arterial hypertension associated with connective tissue disease; CHD-PAH, pulmonary arterial hypertension associated with congenital heart disease; CTEPH, chronic thromboembolic pulmonary hypertension; PaO2, arterial oxygen pressure (daytime); PaCO2, arterial carbon dioxide pressure (daytime); SaO2, arterial oxygen saturation (daytime); NT-proBNP, N-terminal pro B type natriuretic peptide; MPAP, mean pulmonary arterial pressure; PVR, pulmonary vascular resistance; CI, cardiac index; MRAP, mean right atrial pressure; PeakVO2/kg, peak kilogram oxygen uptake; VE/VCO2, carbon dioxide ventilation equivalent

Table 3. Comparison of sleep breathing monitoring indicators in patients with and without OSA
Variable	No OSA	OSA	P value
Numbers	105	35	NS
AHI/h*	1.6 ± 1.2	16.2 ± 12.7	< 0.001
AI,/h*	0.3 ± 0.5	3.9 ± 9.6	< 0.001
OAI,/h*	0.3 ± 0.5	3.3 ± 7.6	< 0.001
CAI,/h	0.0 ± 0.0	0.6 ± 0.5	0.822
Mean SaO2, %*	91.90 ± 4.68	88.89 ± 4.86	0.439
Minimum SaO2, %*	83.52 ± 7.13	75.8 ± 11.55	0.002
SaO2 < 90%, min*	74.97 ± 117.64	166.30 ± 148.17	0.001
SaO2 < 80%, min*	9.81 ± 47.68	19.93 ± 62.81	0.085
SaO2 < 70%, min*	2.51 ± 25.03	5.21 ± 16.12	0.327

Data are presented as mean ± SD or median (interquartile range). AHI, apnoea and hypopnea index; AI, apnoea index; OAI, obstructive apnoea index; CAI, central apnoea index; mean SPO2, mean oxygen saturation (night); minimum SPO2 minimal oxygen saturation (night)

Table 4. Comparison of routine clinical examination values in patients with and without OSA
Variable	No OSA	OSA	P value
Numbers	105	35	NS
Age (years)*	37.06 ± 12.46	46.74 ± 14.25	0.001
Females (N%)*	87 (82.9%)	20 (57.1%)	< 0.001
BMI (kg·m⁻²)	22.32 ± 3.38	25.71 ± 4.13	0.154
SBP (mmHg)	111.28 ± 13.22	118.86 ± 14.71	0.004
DBP (mmHg)	72.26 ± 9.92	76.83 ± 14.79	0.006
NYHA (%)			0.327
1	8 (7.6%)	0 (0%)
2	46 (43.8%)	8 (22.9%)
3	47 (44.8%)	26 (74.3%)
4	4 (3.8%)	1 (2.9%)
Drug therapy	26/68/11	10/19/6	0.852
Targeting medication (none/single/combination)
Positive inotropes	79	21	0.206
Diuretics	94	20	0.335
Supplemental oxygen therapy	21	17	0.117
FEV1	78.67 ± 14.87	74.28 ± 13.60	0.783
FVC	86.13 ± 16.75	84.35 ± 14.28	0.671
FEV1/FVC	94.33 ± 7.82	92.66 ± 8.43	0.562
TLC	83.91 ± 9.65	79.37 ± 8.52	0.942
DLCO	72.75 ± 11.68	70.42 ± 14.72	0.923
PaO₂ (mmHg)*	71.77 ± 15.21	63.69 ± 10.21	0.014
PaCO₂ (mmHg)	35.76 ± 4.74	36.51 ± 11.17	0.843
SaO₂ (%)	93.24 ± 4.71	91.79 ± 3.77	0.199
Epworth score	3.34 ± 3.12	4.67 ± 2.97	0.740
LA (mm)	30.99 ± 6.27	33.2 ± 6.30	0.4433
LV (mm)	37.36 ± 6.79	41.11 ± 7.36	0.609
LVEF (%)	63.02 ± 5.65	61.97 ± 6.54	0.337
RV (mm)	32.27 ± 6.82	33.8 ± 7.71	0.306
sPAP (mmHg)	88.88 ± 22.90	85.52 ± 17.66	0.321
6MWD (m)	418.66 ± 96.40	368.56 ± 120.62	0.337
NT-proBNP (pg/ml)	1126.31 ± 1298.81	1662.47 ± 1493.71	0.553
mPAP (mmHg)*	56.45 ± 18.19	53.57 ± 13.08	0.010
PVR (dyn•s•cm⁻⁵)	1110.86 ± 517.33	1181.54 ± 402.09	0.071
CI (L/min/m²)	3.04 ± 1.34	2.04 ± 1.11	0.730
MRAP (mmHg)	5.97 ± 4.67	6.11 ± 3.89	0.465
Peak VO₂/kg (ml/kg/min)	13.16 ± 3.95	11.08 ± 3.46	0.272
VE/VCO₂	42.27 ± 9.21	45.19 ± 11.29	0.380
VE/VCO2 slope	43.33 ± 15.41	48.48 ± 15.19	0.860

Data are presented as mean ± SD or median (interquartile range). BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; NYHA, New York Heart Association; FEV1, forced expiratory volume at first second; FVC, forced vital capacity; TLC, total lung capacity; DLCO, diffusion capacity for carbon monoxide of the lung; PaO2, arterial oxygen pressure (daytime); PaCO2, arterial carbon dioxide pressure (daytime); SaO2, arterial oxygen saturation (daytime); LA, anteroposterior diameter of left atrium; LV, anteroposterior diameter of left ventricle; LVEF, left ventricular ejection fraction; RV, right ventricular end-diastolic diameter; sPAP, pulmonary artery systolic pressure; 6MWD, six-minute walking distance; NT-proBNP, N-terminal pro B type natriuretic peptide; MPAP, mean pulmonary arterial pressure; PVR, pulmonary vascular resistance; CI, cardiac index; MRAP, mean right atrial pressure; PeakVO2/kg, peak kilogram oxygen uptake; VE/VCO2, carbon dioxide ventilation equivalent; VE/VCO2 slope: the slope of carbon dioxide ventilation equivalent