Non-monotonic cardiovascular adaptation and stroke output-stroke output coupling reorganization in high-altitude adolescents: a cross-sectional study along altitude gradients

Abstract

Abstract Cardiovascular adaptation to chronic high-altitude exposure during adolescence remains incompletely understood because developmental autonomic regulation may differ from adult acclimatization. We examined whether cardiovascular responses vary non-monotonically across altitude, whether stroke output-stroke output coupling is reorganized, and whether nonlinear cardiac complexity is associated with post-exercise recovery. This cross-sectional study included 190 healthy adolescents aged 11–13 years residing at five altitudes (2330–3600 m). We recorded synchronized electrocardiography and noninvasive impedance cardiography at rest, during standardized exercise, and during early recovery. We analyzed hemodynamic indices, heart-rate variability measures (including the root mean square of successive differences and high-frequency power), and nonlinear indices using altitude-specific models, linear mixed-effects models, moderation analysis of the left ventricular ejection time-stroke index relationship, and principal component analysis. Cardiovascular responses were heterogeneous and non-monotonic across altitude. Cardiac index increased particularly around 3500–3600 m, whereas stroke index, left ventricular ejection time, maximum heart rate, and several autonomic indices showed pronounced reorganization around 3500 m with partial rebound at 3600 m. The left ventricular ejection time-stroke index relationship varied by altitude (interaction P < 0.001), supporting altitude-dependent reorganization of stroke output-stroke output coupling. Resting sample entropy showed limited association with heart-rate recovery at 3600 m (R 2 ≈0.080, P≈0.123). In contrast, an exploratory composite complexity index showed a stronger positive association with recovery at 3600 m, although this subgroup finding requires confirmation. Cardiovascular adaptation in high-altitude adolescents is non-monotonic and stage-dependent. Approximately 3500 m may represent a study-specific functional transition region, while nonlinear complexity may provide complementary, but not definitive, information on recovery capacity.