Prevalence and Determinants of Depression and Anxiety in Patients With Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension

Abstract

Background: Depression and anxiety screening has not been adequately examined in patients with pulmonary hypertension (PH). We assessed depression and anxiety prevalence and their determinants in pulmonary arterial hypertension (PAH) and chronic thromboembolic PH (CTEPH).

Methods and Results: This cross-sectional study included 234 patients with PH (age 57 [42–68] years; 75% female; PAH/CTEPH/other: 103/126/5). Overall, 24% and 26% of patients had depression (Hospital Anxiety and Depression Scale [HADS]-depression score ≥8) and anxiety (HADS-anxiety score ≥8) respectively. Depression and anxiety prevalence was 18% and 19% in PAH and 27% and 30% in CTEPH, respectively. Among patients with PAH, depression was significantly associated with higher mean right atrial pressure (odds ratio [OR] 1.17; 95% confidence interval [CI] 1.03–1.32; P=0.013), higher pulmonary vascular resistance (OR 1.08; 95% CI 1.01–1.16; P=0.034), lower arterial oxygen saturation (OR 0.89; 95% CI 0.80–0.98; P=0.021), pulmonary artery oxygen saturation (OR 0.93; 95% CI 0.87–0.99; P=0.020), and reduced use of phosphodiesterase-5 inhibitor (OR 0.30; 95% CI 0.11–0.86; P=0.025). In CTEPH, depression was significantly associated with the presence of a psychiatric disorder (OR 4.71; 95% CI 1.24–17.90; P=0.023). Anxiety was not significantly associated with any of the aforementioned parameters in PAH and CTEPH.

Conclusions: Predicting depression and anxiety based on disease severity and hemodynamics was challenging, making individual assessments and approaches crucial.

Pulmonary hypertension (PH) is comprised of a heterogenous group of progressive disease characterized by sustained elevation of pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR), right ventricular dysfunction, and reduced exercise tolerance.¹ Owing to significant advancements in treatment, such as pulmonary vasodilators and balloon pulmonary angioplasty (BPA), clinical trials have demonstrated improvement in survival and functional capacity of patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic PH (CTEPH).^2,3 Therefore, gaining a better understanding of the impact of PH on patients, extending beyond survival and physical function, will help medical providers in improving health outcomes in patients with PH.

Psychological disturbances are common in patients with cardiovascular disease and are associated with increased mortality, reduced quality of life (QoL), and reduced adherence to healthy lifestyles and evidence-based medical therapies.^4,5 Current clinical guidelines recommend screening patients with cardiovascular diseases for depression and anxiety using validated questionaries.^1,6–9 However, in current clinical settings, including PH management, these psychological disturbances are not adequately examined or treated. Moreover, the prevalence and determinants of depression and anxiety have not been fully elucidated for patients with PH, and whether these aspects vary based on PH etiology is also unknown. By elucidating the determinants of depression and anxiety, medical providers can focus on patients with PH and high-risk of psychological disturbances for further improvement in their health outcomes.

Against this background, this study investigated the prevalence of depression and anxiety in PH and specifically identified their determinants by analyzing clinical characteristics, differences in hemodynamics, and medical therapies in PAH and CTEPH.

Methods

Study Design and Patient Recruitment

This cross-sectional study comprised 234 inpatients with PH admitted to Kyorin University Hospital. The inclusion criteria were as follows: admission for PH treatment and examination at Kyorin University Hospital between 2011 and 2014. Patients who underwent the 6-min walk test (6MWT), right heart catheterization (RHC), and depression and anxiety assessment using the Hospital Anxiety and Depression Scale (HADS) questionnaire were included in the present study. PH diagnosis was conducted in accordance with the European Society of Cardiology/European Respiratory Society (ESC/ERS) Guidelines,¹⁰ involving the confirmation of clinical suspicion based on symptoms and physical findings, along with meeting the hemodynamic assessment criteria. A comprehensive series of tests was performed to elucidate the etiology and functional-hemodynamic severity of the condition.

This study was approved by the Committee for Clinical Studies and Ethics of Kyorin University School of Medicine, Tokyo, Japan. Verbal informed consent was obtained from the enrolled patients before their inclusion, and a separate questionnaire form was collected from each patient.

RHC

RHC was conducted using a transjugular approach with a 6-F double-lumen, balloon-tipped Swan-Ganz catheter (Harmac Medical Products, Inc., Buffalo, NY, USA), as described previously.^11,12 Briefly, baseline hemodynamic data were recorded, and included pulmonary artery wedge pressure (PAWP), right atrial pressure (RAP), PAP, and cardiac output (CO) determined using the Fick method. Oxygen saturation in arterial blood (SaO₂) was measured in the radial or femoral artery, and pulmonary artery oxygen saturation (SvO₂) was also assessed. PVR in Wood units was calculated using the formula: (mean PAP − PAWP) / CO.

6MWT

The 6MWT was performed following established guidelines.¹³ Each participant completed the test in a quiet hospital corridor on a 20 m marked track; chairs were available to provide support when turning if needed. The total distance walked was recorded as the 6-min walk distance (6MWD; to the nearest meter). To ensure adequate risk management, participants were constantly monitored with an electrocardiogram, and peripheral O₂ saturation was measured using a finger pulse oximeter.

HADS

Anxiety and depression were assessed using the HADS, a widely adopted self-reported questionnaire developed to assess anxiety and depression levels in population studies, primary care, and hospital settings.^14,15 The HADS consists of 14-items scored on a 4-point Likert scale (ranging from 0 [not present] to 3 [maximally present]), and is designed to evaluate depression and anxiety separately via the subscales HADS-depression (HADS-D) and HADS-anxiety (HADS-A); each subscale comprises 7 items, allowing for potential subscores between 0 to 21. Depression and anxiety were defined as HADS-D score ≥8 and HADS-A score ≥8, respectively.^14–17

Statistical Analyses

Continuous variables were presented as mean±standard deviation (SD) for normally distributed variables and as median (interquartile range) for non-normally distributed variables. Categorical variables were expressed as absolute values (%). Patients were categorized into 2 groups based on the presence or absence of depression or anxiety as classified using the HADS score. Analyses were performed separately for patients with PAH (Group 1) and CTEPH (Group 4). Comparisons between normally and non-normally distributed variables were performed using the Student’s t-test and the Mann-Whitney U test, respectively. The chi-square test was used to compare categorical variables. The correlation between HADS-D and HADS-A scores was assessed using Spearman›s rank correlation test. A univariate logistic regression analysis was used to evaluate the determinants of depression and anxiety states considering patient backgrounds, hemodynamics, type of PAH (idiopathic PAH [IPAH]/heritable PAH [HPAH], connective tissue disease [CTD-PAH], and congenital heart disease-associated PAH), comorbidities, and treatment administered. Additionally, we compared the clinical variables, including HADS-D and HADS-A scores, between the PAH and CTEPH groups. Statistical significance was set at P<0.05. All statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS; version 26.0; IBM Corp., Armonk, NY, USA).

Results

Patient Characteristics

The study enrolled 234 consecutive patients with PH who were admitted to Kyorin University Hospital between 2011 and 2014. The patients were predominantly female (75%), with a median age of 57 (42–68) years. According to the clinical classification, 103 patients exhibited PAH, and were further categorized into subgroups as follows: IPAH (n=46); HPAH (n=5); CTD-PAH (n=30); congenital heart disease-associated PAH (n=17); portal hypertension-associated PAH (n=4); and HIV-associated PAH (n=1). Additionally, 126 patients exhibited CTEPH, and 5 had other forms of PH (3 with PH associated with lung diseases/hypoxemia, and 2 with PH of unclear etiology or multifactorial causes).

Table 1 presents the characteristics of all patients, distinguishing between those with PAH and CTEPH. Patients with PAH were younger than those with CTEPH (44 [34–56] vs. 63 [53–71] years; P<0.001), and their 6MWD was longer than that of those with CTEPH (431±118 vs. 379±110 m; P<0.001). Additionally, hypertension and hyperlipidemia were significantly more prevalent in CTEPH compared with PAH. In the PAH group, 1 (1%) patient was diagnosed with a psychiatric disorder (depression), whereas within the CTEPH group, 10 (8%) patients had a history of psychiatric disorders (3 cases of depression, 5 bipolar disorders, 2 schizophrenia), with a significantly higher prevalence in CTEPH. Although the mean PAP did not differ significantly between the 2 groups, CO in PAH was higher than that in CTEPH (4.4 [3.4–5.8] vs. 3.8 [3.2–4.7] L/min; P=0.007). Notably, the use of home oxygen therapy was less common in PAH than in CTEPH (3 [3%] vs. 41 [33%]; P<0.001). Among patients with CTEPH, 14 (11%) had previous BPA or pulmonary endarterectomy (PEA).

Table 1.

Baseline Characteristics of the Total Cohort and the PAH and CTEPH Groups

	Total (n=234)	PAH (n=103)	CTEPH (n=126)	P value
Demographics
Age (years)	57 [42–68]	44 [34–56]	63 [53–71]	<0.001
Sex, female	176 (75)	76 (74)	98 (78)	0.482
BMI (kg/m2)	21.7 [19.4–24.2]	21.4 [18.8–23.8]	22.0 [20.2–24.7]	0.102
PAH etiology
IPAH/HPAH/CTD-PAH/congenital/other	–	46/5/30/17/5	–	–
Comorbidity
Hypertension	47 (20)	11 (11)	36 (29)	<0.001
Diabetes	22 (10)	9 (9)	13 (10)	0.687
Hyperlipidemia	46 (20)	11 (11)	35 (28)	0.001
Psychiatric disorder	11 (5)	1 (1)	10 (8)	<0.001
Cancer	9 (4)	4 (4)	5 (4)	0.974
Stroke	2 (1)	1 (1)	1 (1)	0.886
Laboratory data
Hemoglobin (g/dL)	12.9 [11.7–14.1]	13.2 [12.0–14.5]	12.8 [11.5–13.9]	0.424
BNP (pg/mL)	46 [21–105]	35 [11–91]	53 [28–131]	0.128
Exercise endurance
6MWD (m)	400±118	431±118	379±110	<0.001
Hemodynamic data
mRAP (mmHg)	5 [3–7]	5 [3–7]	5 [3–9]	0.111
mPAP (mmHg)	37 [27–45]	38 [28–45]	36 [25–44]	0.052
SaO2 (%)	95 [91–97]	96 [93–97]	94 [91–96]	0.003
SvO2 (%)	69±8	73±8	67±7	<0.001
CO (L/min)	4.1 [3.2–5.0]	4.4 [3.4–5.8]	3.8 [3.2–4.7]	0.007
PVR (Wood unit)	6.7 [3.9–10.1]	6.5 [4.1–9.3]	6.8 [3.8–10.3]	0.603
Therapeutic intervention
HOT	45 (19)	3 (3)	41 (33)	<0.001
Past history of BPA/PEA	14 (6)	–	14 (11)	–
ERA	140 (60)	70 (68)	69 (55)	0.042
Intravenous prostacyclin	35 (15)	35 (34)	–	–
Oral prostacyclin	94 (40)	34 (33)	60 (48)	0.025
PDE5i	159 (68)	76 (74)	81 (64)	0.123

Unless indicated otherwise, data are presented as n (%), mean±standard deviation, or median [interquartile range]. 6MWD, 6-min walk distance; BMI, body mass index; BNP, B-type natriuretic peptide; BPA, balloon pulmonary angioplasty; CO, cardiac output; CTD-PAH, connective tissue disease associated pulmonary arterial hypertension; CTEPH, chronic thromboembolic pulmonary hypertension; ERA, endothelin receptor antagonist; HOT, home oxygen therapy; HPAH, heritable pulmonary arterial hypertension; IPAH, idiopathic pulmonary arterial hypertension; mPAP, mean pulmonary arterial pressure; mRAP, mean right atrial pressure; PAH, pulmonary arterial hypertension; PDE5i, phosphodiesterase type 5 inhibitor; PEA, pulmonary endarterectomy; PVR, pulmonary vascular resistance; SaO₂, arterial oxygen saturation; SvO₂, mixed venous oxygen saturation.

Distribution of Psychological Disturbances

Among the 234 patients in the PH cohort, the median HADS-D and HADS-A scores were 5 (2–7) and 5 (3–8) points, respectively. A significant correlation was observed between HADS-D and HADS-A scores (rs=0.581; P<0.001). In addition, the prevalence of depression was 24%, while anxiety was 26% (Figure 1).

Figure 1.

Frequency distribution of the Hospital Anxiety and Depression Scale (HADS) scores for the total cohort. (A) HADS-depression score; and (B) HADS-anxiety score.

The prevalence of depression was 18% (19 patients) in PAH and 27% (34 patients) in CTEPH (P=0.128). Comparing the 2 groups, patients with PAH displayed significantly lower HADS-D scores than those with CTEPH (4 [2–7] vs. 6 [4–9] points; P=0.004; Figure 2A,B). The prevalence of anxiety was 19% (20 patients) in PAH and 30% (38 patients) in CTEPH (P=0.063), with no significant differences in HADS-A scores between the 2 groups (5 [2–7] vs. 6 [3–8] points; P=0.129; Figure 2C,D).

Figure 2.

Frequency distribution of the Hospital Anxiety and Depression Scale (HADS) scores for the pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) groups. (A) HADS-depression (HADS-D) scores for PAH; (B) HADS-D scores for CTEPH; (C) HADS-anxiety (HADS-A) scores for PAH; and (D) HADS-A scores for CTEPH.

Relationship Between Psychological Disturbances and Clinical Characteristics

We investigated the association between patient clinical characteristics and their experience of depression or anxiety within each subgroup.

Among the patients with PAH cohort, those with depression exhibited a higher mean RAP (6 [5–9] vs. 5 [3–6] mmHg; P=0.014) and lower SaO₂ (94 [91–96] vs. 96 [93–98] %; P=0.017). In terms of treatment, these patients displayed lower use of phosphodiesterase-5 inhibitors (PDE5i; 10 [53%] vs. 66 [79%]; P=0.020) than did patients without depression. In the CTEPH cohort, patients with depression were more likely to have a psychiatric disorder (6 [18%] vs. 4 [4%]; P=0.023) compared with patients without depression. In both the PAH and CTEPH groups, no significant differences in clinical characteristics were observed between patients with and without anxiety (Supplementary Tables 1,2).

Table 2 presents the determinants of depression and anxiety in patients with PAH and CTEPH based on the univariate logistic regression analysis. Regarding patients with PAH, depression was significantly associated with higher mean RAP (odds ratio [OR] 1.17; 95% confidence interval [CI] 1.03–1.32; P=0.013), higher PVR (OR 1.08; 95% CI 1.01–1.16; P=0.034), lower SaO₂ (OR 0.89; 95% CI 0.80–0.98; P=0.021), SvO₂ (OR 0.93; 95% CI 0.87–0.99; P=0.020), and reduced use of PDE5i (OR 0.30; 95% CI 0.11–0.86; P=0.025), but was not associated with patient background, comorbidities, or type of PAH. Conversely, no factors exhibited a significant association with anxiety in these patients. In CTEPH, depression was significantly associated with the presence of a psychiatric disorder (OR 4.71; 95% CI 1.24–17.90; P=0.023), but was not associated with patient background, comorbidities, or treatment. In the sensitivity analysis of patients with CTEPH without psychiatric disorders (n=116), no significant parameters were associated with depression and anxiety.

Table 2.

Univariate Logistic Regression Analysis for Determinants of Depression and Anxiety

	PAH: Depression		PAH: Anxiety		CTEPH: Depression		CTEPH: Anxiety
	OR (95% CI)	P value	OR (95% CI)	P value	OR (95% CI)	P value	OR (95% CI)	P value
Age	1.00 (0.97–1.04)	0.800	1.01 (0.98–1.04)	0.575	0.97 (0.96–1.01)	0.873	1.01 (0.98–1.04)	0.485
Sex, female	0.71 (0.21–2.35)	0.572	1.70 (0.60–4.84)	0.323	1.71 (0.70–4.21)	0.241	1.39 (0.57–3.38)	0.469
BMI	0.96 (0.84–1.09)	0.544	1.12 (1.00–1.25)	0.052	1.05 (0.95–1.16)	0.338	0.93 (0.84–1.04)	0.189
Psychiatric disorder	–	–	–	–	4.71 (1.24–17.90)	0.023	1.61 (0.43–6.06)	0.483
Hypertension	0.98 (0.19–4.96)	0.981	1.65 (0.40–6.90)	0.489	0.87 (0.36–2.10)	0.751	0.85 (0.36–2.00)	0.713
Diabetes	2.44 (0.55–10.80)	0.544	0.49 (0.06–4.20)	0.517	1.23 (0.35–4.29)	0.746	1.03 (0.30–3.59)	0.960
Hyperlipidemia	1.78 (0.43–7.46)	0.430	0.91 (0.18–4.60)	0.913	1.12 (0.47–2.66)	0.803	1.30 (0.57–3.00)	0.532
IPAH/HPAH	0.40 (0.14–1.15)	0.090	1.02 (0.39–2.72)	0.961	–	–	–	–
CTD-PAH	1.55 (0.54–4.41)	0.415	0.55 (0.17–1.80)	0.322	–	–	–	–
Congenital heart disease-PAH	1.46 (0.42–5.09)	0.556	1.97 (0.60–6.44)	0.260	–	–	–	–
6MWD	0.99 (0.99–1.00)	0.155	1.00 (0.99–1.00)	0.411	0.99 (0.99–1.00)	0.674	0.99 (0.99–1.01)	0.121
mRAP	1.17 (1.03–1.32)	0.013	1.12 (1.00–1.26)	0.054	1.08 (0.97–1.20)	0.154	0.98 (0.87–1.09)	0.659
mPAP	1.02 (0.99–1.06)	0.180	0.98 (0.95–1.02)	0.286	1.02 (0.98–1.05)	0.339	1.03 (0.99–1.06)	0.114
SaO2	0.89 (0.80–0.98)	0.021	0.97 (0.87–1.07)	0.488	0.95 (0.85–1.05)	0.324	1.01 (0.91–1.12)	0.839
SvO2	0.93 (0.87–0.99)	0.020	0.96 (0.90–1.02)	0.182	0.97 (0.92–1.03)	0.296	0.99 (0.95–1.05)	0.904
CO	0.73 (0.52–1.04)	0.079	0.76 (0.55–1.07)	0.112	0.94 (0.69–1.28)	0.707	0.85 (0.63–1.17)	0.318
PVR	1.08 (1.01–1.16)	0.034	0.96 (0.87–1.06)	0.410	1.02 (0.94–1.11)	0.658	1.07 (0.99–1.16)	0.108
HOT	–	–	–	–	0.44 (0.17–1.12)	0.087	1.11 (0.50–2.50)	0.793
PEA/BPA	–	–	–	–	0.71 (0.19–2.73)	0.621	1.33 (0.41–4.27)	0.632
ERA	0.44 (0.16–1.23)	0.118	0.38 (0.14–1.04)	0.060	0.90 (0.41–1.99)	0.803	0.65 (0.30–1.40)	0.275
Intravenous prostacyclin	0.64 (0.21–1.96)	0.437	0.42 (0.13–1.37)	0.150	–	–	–	–
Oral prostacyclin	0.32 (0.09–1.19)	0.089	1.46 (0.53–4.00)	0.460	2.20 (0.98–4.91)	0.056	1.55 (0.72–3.34)	0.260
PDE5i	0.30 (0.11–0.86)	0.025	0.45 (0.16–1.25)	0.124	1.47 (0.63–3.45)	0.371	1.55 (0.68–3.52)	0.299

CI, confidence interval OR, odds ratio. Other abbreviations as in Table 1.

Discussion

This study revealed that 24% of patients with PH experienced depression, whereas 26% were anxious. Furthermore, the HADS-D score was lower in patients with PAH compared with those with CTEPH. Among the patients with PAH, significant associations were observed between certain hemodynamic parameters, PH treatment medications, and depression. Among the patients with CTEPH, a significant association was observed between the presence of a psychiatric disorder and depression. No significant determinants of anxiety were observed in either PAH or CTEPH.

Depression and Anxiety Prevalence

Among patients with cardiovascular diseases, psychological disturbances, such as depression and anxiety, are common, warranting the need for screening, especially in cases of coronary artery disease, heart failure (HF), and other cardiovascular disease risk.^4,7–9 The prevalence of depression and anxiety is also reported to be high in patients with PH.^18–33 According to a systematic review and meta-analysis by Mai et al., the prevalence of depression and anxiety in patients with PH is 28% and 37%, respectively.¹⁸ However, this finding is based on the heterogeneous variability in diagnostic methods. In the present study, we used HADS, a commonly used and validated tool. Therefore, using the same questionnaire and cut-off value for diagnosis of depression and anxiety enables a direct comparison of the prevalence of these psychological disturbances in PH and other settings. For instance, among 1,294 patients hospitalized for various cardiovascular diseases (coronary artery disease n=401; HF n=90; arrythmias n=521; valvular heart diseases n=145), 19% experienced depression and 17% experienced anxiety,¹⁷ which was lower than that in our PH cohort (24% depression and 26% anxiety). In prior studies involving hospitalized patients with HF, 52% experienced depression, while 31% experienced anxiety.³⁴ These findings, using the same HADS cut-off values, suggest that depression and anxiety were common in PH, as in other cardiovascular diseases.

The literature on depression and anxiety concerning the etiology of PH remains limited. In a meta-analysis, CTEPH is a significant risk factor for depression, although this finding was affected by variability in diagnostic methods, as discussed previously.¹⁸ Pfeuffer et al. observed a higher prevalence of depression among patients with CTEPH compared with patients with PAH.¹⁹ In our study, despite no observable significant difference in prevalence, the HADS-D scores for patients with CTEPH was higher than those for patients with PAH. Although the ESC/ERS guidelines for PH mainly emphasize the screening of depression in limited settings (delivery in PAH),¹ the screening and management of depression and anxiety needs to be performed for both patients with PAH and CTEPH.

Determinants of Depression and Anxiety

In a meta-analysis involving 24 studies of PH, depression and anxiety significantly correlated with demographics (i.e., age, ethnicity, sex), and functional status. Hemodynamics parameters, such as PVR and cardiac index, were significantly associated with anxiety, but not depression.¹⁸ Despite the significant differences in patient backgrounds and treatment approaches between PAH and CTEPH, in this meta-analysis, the determinants of depression and anxiety was evaluated in the overall PH cohort, which is consistent with previous studies.^{19,22,25,27,32} Notably, the number of patients enrolled in our study cohort (n=234) was higher than that of the 24 studies included in this meta-analysis.¹⁸ Furthermore, in most of the studies, including both PAH and CTEPH,¹⁸ the number of patients with CTEPH was less than 30, which made it difficult to evaluate the determinants of depression and anxiety in PAH and CTEPH separately. In our study, depression in PAH was weakly associated with a higher mean RAP, lower SaO₂ and SvO₂, higher PVR, and reduced usage of PDE5i. Conversely, the determinants of anxiety in PAH and CTEPH remained unidentified.

Several small-sample size cohorts of homogenous etiology of PH (mainly PAH), have evaluated the determinants of depression or anxiety.^23,26,28 In a study by Zhang et al., in patients with PAH, depression and anxiety were found to be associated with deterioration in physical function evaluated based on 6MWD, functional classification, and mean PAP,²³ which is not consistent with our study. One possible reason for this discrepancy could be the use of different depression screening tools; Zhang et al. used the Self Rating Depression Scale, which differs from ours. Additionally, Zhang et al.’s study population displayed higher mean PAP and greater disease severity compared with our study group (mean PAP 44±13 vs. 38 [28–45] mmHg). In terms of CTEPH, previous studies revealed inconsistent results regarding the association of psychological disturbances with non-pharmacological interventions. Takita et al. suggested that patients who do not undergo BPA are at risk of developing depression and anxiety.²⁰ Conversely, Vanini et al. demonstrated that PEA decreased HADS-D and HADS-A scores.²⁹ However, our study did not show a significant impact on HADS-D scores based on the implementation of PEA or BPA. Dering et al. also reported that the prevalence of mental disorders in CTEPH was not related to interventional or surgical treatment or disease severity.²¹ While BPA improves patients’ health-related QoL,³⁵ its impact on psychological disturbances remains unknown. As the proportion of patients who underwent PEA/BPA in our CTEPH group was low (11%), future research involving a randomized control study or large multicenter cohort is needed to ascertain the effects of interventions on mental well-being.

Approaches for Future Interventions

As reported by Löwe et al., only 24.1% of individuals with mental disorders among patients with PAH have received pharmacological or psychological/psychotherapeutic treatment.³² While cognitive-behavioral therapy is predominantly recommended as psychological intervention for patients with depressive states in the general population, the efficacy of psychological and pharmacological interventions for patients with PH is not fully elucidated. Previous studies have indicated a significant reduction in levels of anxiety and depression when incorporating slow breathing concurrently with psychological interventions, along with a decrease in interleukin-6 levels associated with the pathophysiology of PH.^36–38

Mindfulness-based stress reduction, proves effective in alleviating depressive and anxiety symptoms among patients with breast cancer,³⁹ and holds promise for positively impacting the mental well-being of patients with PH. Progressive muscle relaxation (PMR) is also considered effective as an intervention for PH. In a prior study by Li et al., PMR resulted in reduced HADS-D and HADS-A scores, suggesting a contribution to the improvement of depression and anxiety in patients with PH.³⁰ The ESC/ERS guidelines emphasize the need for appropriate screening to identify patients who would benefit from psychological/psychiatric support, pharmacological treatment, and social assistance.¹ Future research should focus on identifying patients who would gain maximum benefit from these interventions.

Study Limitations

This study has several limitations. This was a single-center study, and the number of patients enrolled was small; therefore, the statistical power of this study may have been insufficient. Additionally, we included only Asian patients, and the generalizability of our findings to other races is limited. Furthermore, our study adopted a cross-sectional observational design, which limited our ability to establish causal relationships. The absence of information regarding illness duration, social background, family dynamics, employment status, and income leaves the relationship between these factors and a patient’s mental state unknown.

Conclusions

The prevalence of depression and anxiety in PH was notably high, similar to that in other cardiovascular diseases. Predicting depression and anxiety states based on disease severity and hemodynamics in PH is challenging, and individual assessment and approaches are crucial.

Sources of Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Disclosures

The authors declare that there are no conflicts of interest.

IRB Information

This study was approved by the Committee for Clinical Studies and Ethics of the Kyorin University School of Medicine, Tokyo, Japan (1595-02).

Data Availability

The deidentified participant data will not be shared.

Supplementary Files

Please find supplementary file(s);

https://doi.org/10.1253/circrep.CR-24-0113

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