The comorbidity burden and disease phenotype in pre-capillary pulmonary hypertension: The contributing role of obstructive sleep apnea

Abstract

Background: Pre-capillary pulmonary hypertension (PH) with risk factors for left ventricular diastolic dysfunction, described as an atypical phenotype of "mixed" pre- and post-capillary PH, has become a research focus. However, the relationship between obstructive sleep apnea (OSA), a known risk factor for cardiometabolic conditions, and comorbidity burden and disease phenotype in PH remains unclear.

Objective: This study aimed to investigate the effect of the presence and severity of OSA on the left ventricular function, comorbidity burden and disease phenotype in pre-capillary PH patients.

Methods and results: We retrospectively examined 450 consecutive pre-capillary PH patients undergoing cardiorespiratory polygraphy and right heart catheterization between May 2020 to November 2021 at Fuwai Hospital. The prevalence of OSA was 34.2%, and the presence and severity of OSA in pre-capillary PH patients was associated with increased left heart mass index (P < 0.001), pulmonary arterial wedge pressure (P = 0.06) and H₂FPEF score (P < 0.001). After adjustment for confounding factors, the severity of OSA measured as apnea-hypopnea index (AHI) was an independent risk factor associated with obesity, systemic hypertension, diabetes mellitus and an atypical phenotype (OR: 1.054, P = 0.004) in pre-capillary PH. A dose-response relationship was also identified between sleep parameters (AHI, oxygen desaturation index, the percentage of sleep time with oxygen saturation<80%) and the number of key comorbidities. Patients with ≥3 comorbidities (atypical phenotype) were older, experienced negative alterations in left ventricular structure and function, and were at a higher risk of OSA.

Conclusion: OSA is relatively prevalent in pre-capillary PH patients, independently associated with the presence of a variety of comorbidities and the atypical phenotype of PH. These findings highlight the importance of OSA as a modifiable target for optimal treatment in PH with comorbidities.

Keywords: Comorbidity; Left heart disease; Phenotype; Pulmonary hypertension; Sleep apnea.