Dissociation between Polycythemia and Symptoms of Chronic Mountain Sickness in Dwellers of the Highest City in the World

Background: While millions of people are living permanently at high altitude (>2500m) worldwide, the mechanisms underlying their tolerance to chronic hypoxia and those responsible for the occurrence of chronic mountain sickness (CMS) remain to be elucidated. Excessive erythrocytosis (EE) is thought to be the main mechanism responsible for CMS symptoms and is included in the definition of CMS but the precise interplay between EE and CMS has been poorly described. Methods: The present study benefits from an exceptional dataset coming from 1594 dwellers of La Rinconada, the highest city in the world (5100-5300m). Based on individual clinical characteristics, subjects were categorized according to i) the presence of EE, ii) CMS symptoms severity and iii) CMS diagnosis based on current guidelines. Findings: The prevalence of EE (44%) and CMS diagnosis (26%) was high compared to other highlander populations. Individuals with EE reported few symptoms while symptomatic individuals had lower hematocrit compared to asymptomatic counterparts. Multivariable analysis revealed that age and sex are the main factors associated with EE while age, hematocrit and number of years living at La Rinconada are factors associated with CMS symptoms. Interpretation: High hematocrit values may be required to reside in La Rinconada with limited symptoms. These results might question the classical definition of CMS in such high altitude population. Funding Statement: This work was supported by the ‘‘Fonds de dotation AGIR pour les maladies chroniques’’ and by the French National Research Agency (ANR-12-TECS-0010) in the framework of the ‘‘Investissements d’avenir’’ program (ANR-15-IDEX-02). Declaration of Interests: All authors have no conflict of interest related to the present work to disclose. Ethics Approval Statement: The study was approved by the ethics committees of Inter-region Rhone-Alpes-Auvergne (IRB-5891) and Universidad Nacional Mayor de San Marcos (CIEI-2019-002).