The Impact of Cardiovascular and Lung Comorbidities in Patients with Pulmonary Arterial Hypertension: A Systematic Review and Meta-analysis

Abstract

BackgroundContemporary patients with pulmonary arterial hypertension (PAH) are older and exhibit cardiovascular and/or lung comorbidities. Such patients have typically been excluded from major PAH drug trials. This systematic review compares baseline characteristics, hemodynamic parameters, and mortality rate between PAH patients with significant number of comorbidities compared to those with fewer or no comorbidities. ΜethodsA systematic literature search in PubMed and Cochrane databases was conducted searching for studies comparing PAH patients with more than two cardiovascular comorbidities and/or at least a lung comorbidity against those with fewer comorbidities. ResultsSeven observational studies were included. PAH patients with comorbidities were older, with an almost equal female-to-male ratio, shorter 6-minute walk distance, higher NT-proBNP levels, and lower lung diffusion for carbon monoxide. In terms of hemodynamics, they had higher mean right atrial pressure and pulmonary artery wedge pressure, lower mean pulmonary arterial pressure, pulmonary vascular resistance and mixed venous oxygen saturation. Pooled analysis of six studies demonstrated a higher mortality risk for PAH patients with comorbidities compared to those without (HR 1.86, 95% CI 1.20 to 2.89, p<0.001, I²=92%), with the subgroup of PAH patients with lung comorbidities having an even higher mortality risk (test for subgroup differences: p<0.001). Combination drug therapy for PAH was less frequently used in patients with comorbidities. ConclusionsCardiovascular and lung comorbidities impact the clinical characteristics and outcomes of PAH patients, highlighting the need for optimal phenotyping and tailored management for this high-risk population.