The burden of comorbidities in pulmonary arterial hypertension

Abstract

Patients with comorbidities are often excluded from clinical trials, limiting the evidence base for pulmonary arterial hypertension (PAH)-specific therapies. This review aims to discuss the effect of comorbidities on the diagnosis and management of PAH. The comorbidities discussed in this review (systemic hypertension, obesity, sleep apnoea, clinical depression, obstructive airway disease, thyroid disease, diabetes, and ischaemic cardiovascular event) were chosen based on their prevalence in patients with idiopathic PAH in the REVEAL registry (Registry to EValuate Early and Long-term PAH disease management). Comorbidities can mask the symptoms of PAH, leading to delays in diagnosis and also difficulty evaluating disease progression and treatment effects. Due to the multifactorial pathophysiology of pulmonary hypertension (PH), the presence of comorbidities can lead to difficulties in distinguishing between Group 1 PH (PAH) and the other group classifications of PH. Many comorbidities contribute to the progression of PAH through increased pulmonary artery pressures and cardiac output, therefore treatment of the comorbidity may also reduce the severity of PAH. Similarly, the development of one comorbidity can be a risk factor for the development of other comorbidities. The management of comorbidities requires consideration of drug interactions, polypharmacy, adherence and evidence-based strategies. A multidisciplinary team should be involved in the management of patients with PAH and comorbidities, with appropriate referral to supportive services when necessary. The treatment goals and expectations of patients must be managed in the context of comorbidities.

Keywords: Comorbidities; Diagnosis; Management; Pulmonary arterial hypertension; Treatment.

Figure 1

The burden of comorbidities observed across pulmonary hypertension groups at the time of diagnosis in authors’ experience.^aComorbidities that are typically associated with pulmonary hypertension Group 5, but may affect all groups. ^bComorbidities that are typically associated with IPAH, but may affect all groups. This schematic is used to illustrate the typical scenarios the authors observe in clinic; it is not drawn to scale and is largely based on authors own experience rather than a robust body of evidence in the literature. The blue triangle and the rectangular ‘Group’ boxes represent the burden of comorbidity and thus, the placement of the pulmonary hypertension group boxes within the triangle, as well as their size, represent the relative prevalence of comorbidities in each group (with the lowest and largest group having the greatest prevalence). Group 5 pulmonary hypertension is shown outside the triangle because published data and the authors’ findings from the clinic are not sufficient to draw conclusions from; there is no consensus on the prevalence of comorbidities in Group 5 pulmonary hypertension at the time of diagnosis. COPD, chronic obstructive pulmonary disease; IPAH, idiopathic pulmonary arterial hypertension; PH, pulmonary hypertension.

Figure 2

Comorbidities that have been reported in patients with idiopathic pulmonary arterial hypertension. Comorbidities are those reported in the REVEAL registry and supplemented by the authors’ clinical experience. COPD, chronic obstructive pulmonary disease.