Association between physiological responses after exercise at low altitude and acute mountain sickness upon ascent is sex-dependent.

BACKGROUND: Acute mountain sickness (AMS) is the mildest form of acute altitude illnesses, and consists of non-specific symptoms when unacclimatized persons ascend to elevation of ≥2500 m. Risk factors of AMS include: the altitude, individual susceptibility, ascending rate and degree of pre-acclimatization. In the current study, we examined whether physiological response at low altitude could predict the development of AMS. METHODS: A total of 111 healthy adult healthy volunteers participated in this trial; and 99 (67 men and 32 women) completed the entire study protocol. Subjects were asked to complete a 9-min exercise program using a mechanically braked bicycle ergometer at low altitude (500 m). Heart rate, blood pressure (BP) and pulse oxygen saturation (SpO2) were recorded prior to and during the last minute of exercise. The ascent from 500 m to 4100 m was completed in 2 days. AMS was defined as ≥3 points in a 4-item Lake Louise Score, with at least one point from headache wat 6-8 h after the ascent. RESULTS: Among the 99 assessable subjects, 47 (23 men and 24 women) developed AMS at 4100 m. In comparison to the subjects without AMS, those who developed AMS had lower proportion of men (48.9% vs. 84.6%, P < 0.001), height (168.4 ± 5.9 vs. 171.3 ± 6.1 cm, P = 0.019), weight (62.0 ± 10.0 vs. 66.7 ± 8.6 kg, P = 0.014) and proportion of smokers (23.4% vs. 51.9%, P = 0.004). Multivariate regression analysis revealed the following independent risks for AMS: female sex (odds ratio (OR) =6.32, P < 0.001), SpO2 change upon exercise at low altitude (OR = 0.63, P = 0.002) and systolic BP change after the ascent (OR = 0.96, P = 0.029). Women had larger reduction in SpO2 after the ascent, higher AMS percentage and absolute AMS score. Larger reduction of SpO2 after exercise was associated with both AMS incidence (P = 0.001) and AMS score (P < 0.001) in men but not in women. CONCLUSIONS: Larger SpO2 reduction after exercise at low altitude was an independent risk for AMS upon ascent. Such an association was more robust in men than in women. TRIAL REGISTRATION: Chinese Clinical Trial Registration, ChiCTR1900025728 . Registered 6 September 2019.

EPAS1 and VEGFA gene variants are related to the symptoms of acute mountain sickness in Chinese Han population: a cross-sectional study.

BACKGROUND: More people ascend to high altitude (HA) for various activities, and some individuals are susceptible to HA illness after rapidly ascending from plains. Acute mountain sickness (AMS) is a general complaint that affects activities of daily living at HA. Although genomic association analyses suggest that single nucleotide polymorphisms (SNPs) are involved in the genesis of AMS, no major gene variants associated with AMS-related symptoms have been identified. METHODS: In this cross-sectional study, 604 young, healthy Chinese Han men were recruited in June and July of 2012 in Chengdu, and rapidly taken to above 3700 m by plane. Basic demographic parameters were collected at sea level, and heart rate, pulse oxygen saturation (SpO2), systolic and diastolic blood pressure and AMS-related symptoms were determined within 18-24 h after arriving in Lhasa. AMS patients were identified according to the latest Lake Louise scoring system (LLSS). Potential associations between variant genotypes and AMS/AMS-related symptoms were identified by logistic regression after adjusting for potential confounders (age, body mass index and smoking status). RESULTS: In total, 320 subjects (53.0%) were diagnosed with AMS, with no cases of high-altitude pulmonary edema or high-altitude cerebral edema. SpO2 was significantly lower in the AMS group than that in the non-AMS group (P = 0.003). Four SNPs in hypoxia-inducible factor-related genes were found to be associated with AMS before multiple hypothesis testing correction. The rs6756667 (EPAS1) was associated with mild gastrointestinal symptoms (P = 0.013), while rs3025039 (VEGFA) was related to mild headache (P = 0.0007). The combination of rs6756667 GG and rs3025039 CT/TT further increased the risk of developing AMS (OR = 2.70, P < 0.001). CONCLUSIONS: Under the latest LLSS, we find that EPAS1 and VEGFA gene variants are related to AMS susceptibility through different AMS-related symptoms in the Chinese Han population; this tool might be useful for screening susceptible populations and predicting clinical symptoms leading to AMS before an individual reaches HA. TRIAL REGISTRATION: Chinese Clinical Trial Registration, ChiCTR-RCS-12002232 . Registered 31 May 2012.