AUTHOR=Yang Jie , Tan Hu , Sun Mengjia , Chen Renzheng , Zhang Jihang , Liu Chuan , Yang Yuanqi , Ding Xiaohan , Yu Shiyong , Gu Wenzhu , Ke Jingbin , Shen Yang , Zhang Chen , Gao Xubin , Li Chun , Huang Lan 

TITLE=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

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=8

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.719776

DOI=10.3389/fcvm.2021.719776

ISSN=2297-055X

ABSTRACT=<p>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], &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<sub>2</sub>) of post-submaximal exercise at SL and <italic>EPAS1</italic> rs13419896-A and <italic>EGLN1</italic> rs508618-G variants were associated with HA-CRFi (SpO<sub>2</sub>, area under the curve (AUC) = 0.736, cutoff = 95.5%, <italic>p</italic> &lt; 0.001; <italic>EPAS1 A</italic> and <italic>EGLN1 G</italic>, odds ratio [OR] = 12.02, 95% CI = 4.84–29.85, <italic>p</italic> &lt; 0.001). A combination model including the two risk factors—post-submaximal exercise SpO<sub>2</sub> at SL of &lt;95.5% and the presence of <italic>EPAS1</italic> rs13419896-A and <italic>EGLN1</italic> rs508618-G variants—was significantly more effective and accurate in predicting HA-CRFi (OR = 19.62, 95% CI = 6.42–59.94, <italic>p</italic> &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.</p>