Exaggerated exercise-induced hypoxic pulmonary pressure in HAPE-prone extend to the next generation

Background High-altitude pulmonary edema (HAPE) is a life-threatening condition occurring in otherwise healthy individuals exposed to altitudes >2500 m. One of the main characteristics of HAPE is the presence of an exaggerated hypoxic pulmonary artery pressure (PAP). Despite advances in medicine, HAPE-aetiology remain unclear. Inheritance was pointed out to increase HAPE susceptibility in offspring but this information is sparse. Purpose The aim of this study was to assess if exaggerated hypoxic PAP and vascular dysfunction observed in HAPE-prone is also present in their offspring. Materials and Methods To address this issue, cardiovascular and pulmonary phenotyping were assessed in HAPE-prone subjects and their offspring, and compared them to HAPE-resistant and their offspring. Systolic PAP (sPAP) was estimated by echocardiography during exercise normobaric hypoxia induced with an altitude simulator (AltiTrainer). Post-exercise lung ultrasound assessed comet tails as a marker of subclinical pulmonary interstitial fluid accumulation. Systemic vascular evaluation included flow-mediated dilation (FMD), carotid intima–media thickness (IMT), pulse wave velocity (PWV), and 24-hour ambulatory blood pressure monitoring (ABPM). Statistical analyses were performed using one- and two-way ANOVA. Results Fifty participants were enrolled (≥10 per group). sPAP were similar in all groups at rest, but significantly higher during exercise in HAPE-prone (p<0.001). Most importantly, offspring of HAPE-prone individuals exhibited a significantly greater hypoxia-induced sPAP increase than both HAPE-resistant adults and their offspring (p<0.001). Comet tails were twofold increased in HAPE-prone compared to the other groups (p<0.001) and similar among HAPE-prone and HAPE-resistant offspring. Vascular parameters are summarized in table 1. Conclusion Our findings shows that offspring of HAPE-prone individuals exhibit enhanced pulmonary vascular reactivity to hypoxia compared with HAPE-resistant and their offspring, though less pronounced than in affected parents. These data suggest that key features of the HAPE-prone phenotype may extend to the next generation. Further mechanistic and longitudinal studies are warranted to clarify the genetic and developmental basis of this phenomenon.