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Insufficient cardiorespiratory compensation is closely associated with acute hypoxic symptoms and high-altitude (HA) cardiovascular events. To avoid such adverse events, predicting HA cardiorespiratory fitness impairment (HA-CRFi) is clinically important. However, to date, there is insufficient information regarding the prediction of HA-CRFi. In this study, we aimed to formulate a protocol to predict individuals at risk of HA-CRFi. We recruited 246 volunteers who were transported to Lhasa (HA, 3,700 m) from Chengdu (the sea level [SL], &amp;lt;500 m) through an airplane. Physiological parameters at rest and during post-submaximal exercise, as well as cardiorespiratory fitness at HA and SL, were measured. Logistic regression and receiver operating characteristic (ROC) curve analyses were employed to predict HA-CRFi. We analyzed 66 pulmonary vascular function and hypoxia-inducible factor- (HIF-) related polymorphisms associated with HA-CRFi. To increase the prediction accuracy, we used a combination model including physiological parameters and genetic information to predict HA-CRFi. The oxygen saturation (SpO 2 ) of post-submaximal exercise at SL and  EPAS1  rs13419896-A and  EGLN1  rs508618-G variants were associated with HA-CRFi (SpO 2 , area under the curve (AUC) = 0.736, cutoff = 95.5%,  p  &amp;lt; 0.001;  EPAS1 A  and  EGLN1 G , odds ratio [OR] = 12.02, 95% CI = 4.84–29.85,  p  &amp;lt; 0.001). A combination model including the two risk factors—post-submaximal exercise SpO 2  at SL of &amp;lt;95.5% and the presence of  EPAS1  rs13419896-A and  EGLN1  rs508618-G variants—was significantly more effective and accurate in predicting HA-CRFi (OR = 19.62, 95% CI = 6.42–59.94,  p  &amp;lt; 0.001). Our study employed a combination of genetic information and the physiological parameters of post-submaximal exercise at SL to predict HA-CRFi. Based on the optimized prediction model, our findings could identify individuals at a high risk of HA-CRFi in an early stage and reduce cardiovascular events.

frontiers in cardiovascular medicine

Prediction of High-Altitude Cardiorespiratory Fitness Impairment Using a Combination of Physiological Parameters During Exercise at Sea Level and Genetic Information in an Integrated Risk Model