Abstract
<jats:p>Background: Permanent residents at extreme altitudes face severe chronic hypoxia, driving excessive erythrocytosis (EE) and chronic mountain sickness (CMS). However, the clinical spectrum of EE remains poorly characterized, and standardized diagnostic criteria (e.g., the Qinghai CMS score) may lack phenotypic accuracy at extreme elevations. This study aims to characterize the specific clinical features associated with an expanded red blood cell mass in extreme-altitude inhabitants. Methods: A cross-sectional study was conducted in La Rinconada, Peru (&gt;5,100 m), the highest permanent human settlement. The cohort comprised 117 adult residents (73 men, 44 women). We evaluated the association between hemoglobin (Hb) concentrations and systemic symptomatology using standardized clinical assessments and validated instruments, including the Harvard Step Test (HST), Headache Impact Test (HIT-6), Mini Tinnitus Questionnaire, Douleur Neuropathique 4 (DN4), mMRC dyspnea scale, PSQI, and Montreal Cognitive Assessment (MoCA). Results: Clinical profiling revealed a non-linear, symptom-specific relationship between Hb levels and clinical manifestations. Elevated Hb correlated with decreased cardiovascular fitness (HST, p&lt;0.001) and increased dizziness. Paradoxically, individuals with relatively lower Hb levels experienced higher intensities of oppressive chest pain (p&lt;0.001) and more disabling headaches (HIT-6, p=0.005). Furthermore, higher Hb was significantly associated with preserved cognitive function (MoCA, p&lt;0.05). Crucially, Hb levels showed no significant association with classic CMS symptoms such as dyspnea, cyanosis, paresthesias, or sleep disturbances. Conclusions: At extreme altitudes, EE exhibits a dual pathophysiological nature—acting as a vital compensatory mechanism for neurocognitive preservation while simultaneously driving hemodynamic compromise. The stark dissociation between absolute red blood cell mass and classic CMS symptomatology challenges current diagnostic paradigms, highlighting the urgent clinical need to recalibrate CMS diagnostic criteria for extreme-altitude populations.</jats:p>