Health-related quality of life and disease progression in pulmonary arterial hypertension patients: a 3-year study

Discussion

This study demonstrates a positive, independent association between progression-free survival and the SF-36 HRQoL PF subscale score in a 55-patient PAH cohort with no loss to follow-up over a 3-year period. Unexpectedly, PF and both the MCS and PCS scores were stable over the entire study period. Progression-free survival was associated with clinical findings comprising negative relationships with mean pulmonary arterial pressure and cardiac output. A battery of baseline psychological tests further demonstrated differences between the stable and disease-progression patient groups that complement differences in HRQoL. Specifically, depression was negatively associated with the PF subscale.

Risk assessment in PAH currently relies on parameters from clinical, haemodynamic, echographic, cardiopulmonary exercise testing and specific biomarker assessments. HRQoL has never been previously assessed in this regard. Surprisingly, HRQoL did not statistically decline over time. However, baseline values were associated with disease progression. This reinforces the results of a retrospective study by McCabe et al. [17] suggesting that the predictive value of the CAMPHOR Questionnaire is also restricted to baseline values. These results suggest that HRQoL monitoring can provide additional useful and complementary information to the traditional PAH work-up, but does not need to be carried out at overly frequent intervals.

In addition, several psychological variables differed between the progression-free and disease-progression groups at baseline, indicating that the latter individuals have stronger anxiety (trait and state anxiety) and depression and resort more often to emotional coping strategies to deal with daily stressors. However, at the multivariable level, the only psychological variable associated with HRQoL was depression. The reader should note that the study cohort included one-quarter incident patients, and these patterns may be specific to patients in the process of disease discovery.

As specifically concerns coping with stressful life events (WCC) and with the disease (CHIP), baseline values for the total population highlighted strategies that were primarily problem-focused, indicating a tendency to want to control the situation [16]. However, in the disease-progression group, such coping strategies (WCC) were more focused on emotional responses. Additionally, when examining the relationships between baseline psychological variables and the HRQoL PF subscale, a significant negative association with the CHIP Emotion score was demonstrated.

People living with PAH are particularly vulnerable when they are newly diagnosed or when they have to deal with the loss of a fellow patient or with a change in treatment. Emotion-focused coping may be the only realistic option when the source of stress is outside the person's control. Furthermore, emotion-focused coping is usually linked to poor HRQoL and associated with symptoms of depression and anxiety [18], as for our PAH disease-progression group.

Previous studies have remarked upon the presence of (presumably) state anxiety, which can be observed to accumulate or peak during: 1) the waiting-for-a-diagnosis period [19], 2) the moment when a PAH diagnosis is announced, or just prior to 3) key progression-determining exams such as right heart catheterisation [20] or 6MWT (in our clinical experience). An additional key moment is the initiation of prostacyclin treatment as well demonstrated by Shafazand et al. [13], where state anxiety decreases during treatment. An amelioration of mood disorders following PAH diagnosis and treatment has been previously observed [21].

Our results place a new-found importance on trait anxiety, i.e. a nonmodifiable and functional personality trait. Patients with an anxious personality type are likely to have a poorer HRQoL, regardless of incident/prevalent status or therapy type (bi- or tri-therapies) [16]. This observation in PAH is important because in-depth work on their life story will be more beneficial than exposure to fears as in behavioural and cognitive therapies designed to help manage state anxiety.

It is also quite interesting that depression was associated with the HRQoL PF score during multivariable analysis. The association of depression with decreased physical functioning has already been reported [22], and depression has been previously demonstrated as a predictor of reduced HRQoL [23]. Depression is common following the diagnosis of a serious illness. Depression disturbs thought and action and these problematic side-effects may interfere with a PAH patient's already compromised HRQoL. Associated directions of causality (Does physical degradation automatically lead to depression? Are non-depressed patients adapting better to PAH? Does depression lead to a more pessimistic self-assessment of HRQoL PF?) remain to be determined.

The PF subscale is designed to examine a person's perceived limitation in performing any physical activity [8]. It reflects a wide range of physical disability, which can cause significant changes in family life, financial situations and social interactions. All such perceived physical limitations can cause depression or be accentuated thereby; for example, certain patients may give up walking exercises to avoid the anxiety they cause. Fatigue and lack of energy may therefore be due to PAH and/or depression. Depression, like PAH, is difficult to recognise and understand, and in depression as in PAH, the suffering is internal, with few visible external signs. Identifying and treating depression is therefore essential.

The limitations of this study include its observational, single-centre nature and sample size, although the latter is actually quite large compared to most PAH studies and reflects the relative rarity of the disease. In addition, disease-specific quality of life tools, such as the CAMPHOR [24], have not been validated in French. As a result, and due to the lack of a minimally clinical important difference for the CAMPHOR [7] and a demonstrated lack of predictive value for repeated CAMPHOR measures [17], we chose a generic measure (the SF-36). The latter, although known to be highly correlated with the CAMPHOR [25], may not be as sensitive to changes in PAH populations [26]. In this case, the patterns in this paper can be considered as conservative in nature. Many authors in the domain have chosen the SF-36 over disease-specific tools even when the latter exist in their languages because it is better known, rapid, easy and reliable [5, 7]. Additionally, the SF-36 has been demonstrated as responsive to change in PAH drug trials [27]. It is also surprising to find that 6MWT distance >400 m was not retained at the multivariate level (table 4) as it has been demonstrated as quite predictive in previous studies [28]. However, this is probably due to the small sample sizes involved. Utmost care was also taken to convince patients to participate in follow-up activities, and our dataset reports no loss to follow-up, which is a great strength. A further strength is the power-supporting, repeated, 3-monthly measures of HRQoL, which, to our knowledge, have not been previously reported for PAH populations.

Finally, the patients included in this cohort were treated for anxiety and depression, including in-house psychological support every 3 months if needed and at times of acute disease decline, in accordance with current recommendations [4]. Guidelines for the use of psychological tests stress that the administration of psychological assessments via telephone, via postal mail, in the presence of a doctor, or in the absence of a psychologist, without knowledge of the patient's psychological status on a given day, are all sources of bias that commonly appear in the literature [29] and that do not apply to the present study. How this might have affected our results in comparison with previous studies should be taken into account.

In conclusion, the positive independent association between the HRQoL PF subscale and progression-free survival starts at baseline, indicating that HRQoL is important complementary information in the work-up of PAH patients. The frequency of psychological symptoms is relatively high, but only depression is independently associated with HRQoL. Lastly, it is interesting to note that HRQoL, which was stable over time in the present cohort, was associated with depression that is also known to be potentially chronic over time. Identifying and treating depression is a major issue in the management of PAH. The patient's point of view regarding his/her health status is essential in decision-making procedures, and future studies by our team will focus on the words patients use to describe their disease, moods, behaviours and HRQoL. Given its independent association with decline, HRQoL should be further studied to elucidate its prognostic potential.