Menopause and High Altitude: A Scoping Review-UIAA Medical Commission Recommendations.

Mateikaite-Pipiriene, Kaste, Dominique Jean, Peter Paal, Lenka Horakova, Susi Kriemler, Alison J. Rosier, Marija Andjelkovic, Beth A. Beidleman, Mia Derstine, Jacqueline Pichler Hefti, David Hillebrandt, and Linda E. Keyes for the UIAA MedCom writing group on Women's Health in the Mountains. Menopause and high altitude: A scoping review-UIAA Medical Commission Recommendations. High Alt Med Biol. 25:1-8, 2024. Background: Older people are an important fraction of mountain travelers and climbers, many of them postmenopausal women. The aim of this work was to review health issues that older and postmenopausal women may experience at high altitude, including susceptibility to high-altitude illness. Methods: We performed a scoping review for the UIAA Medical Commission series on Women's Health in the mountains. We searched PubMed and Cochrane libraries and performed an additional manual search. The primary search focused on articles assessing lowland women sojourning at high altitude. Results: We screened 7,165 potential articles. The search revealed three relevant articles, and the manual search another seven articles and one abstract. Seven assessed menopausal low-altitude residents during a high-altitude sojourn or performing hypoxic tests. Four assessed high-altitude residents. We summarize the results of these 11 studies. Conclusions: Data are limited on the effects of high altitude on postmenopausal women. The effects of short-term, high-altitude exposure on menopause symptoms are unknown. Menopause has minimal effect on the physiological responses to hypoxia in physically fit women and does not increase the risk of acute mountain sickness. Postmenopausal women have an increased risk of urinary tract infections, which may be exacerbated during mountain travel. More research is needed on the physiology and performance of older women at high altitude.

[Application of quantitative proteomics in the study of acute mountain sickness].

Acute mountain sickness (AMS) is a clinical syndrome of multi-system physiological disorder after acute exposure to low pressure and low oxygen at high altitude. Quantitative proteomics can systematically quantify and describe protein composition and dynamic changes. In recent years, quantitative proteomics has been widely used in the prevention, diagnosis, treatment and pathogenesis of many diseases. This review summarizes the progress of quantitative proteomics techniques and its application in the prevention, diagnosis, treatment of AMS and mechanisms of rapidly acclimatizing to plateau, in order to provide a reference for the pathogenesis, early intervention, clinical treatment and proteomic research of AMS.

Acute Mountain Sickness and High Altitude Cerebral Edema in Women: A Scoping Review-UIAA Medical Commission Recommendations.

Derstine, Mia, Dominique Jean, Beth A. Beidleman, Jacqueline Pichler Hefti, David Hillebrandt, Lenka Horakova, Susi Kriemler, Kasté Mateikaité-Pipiriené, Peter Paal, Alison Rosier, Marija Andjelkovic, and Linda E. Keyes. Acute mountain sickness and high altitude cerebral edema in women: A scoping review-UIAA Medical Commission recommendations. High Alt Med Biol. 24:259-267, 2023. Background: Acute mountain sickness (AMS) and high-altitude cerebral edema (HACE) are illnesses associated with rapid ascent to altitudes over 2,500 m in unacclimatized lowlanders. The aim of this scoping review is to summarize the current knowledge on sex differences in the epidemiology, pathophysiology, symptomatology, and treatment of AMS and HACE, especially in women. Methods and Results: The UIAA Medical Commission convened an international author team to review women's health issues at high altitude and to publish updated recommendations. Pertinent literature from PubMed and Cochrane was identified by keyword search combinations (including AMS, HACE, and high altitude), with additional publications found by hand search. The primary search focus was for articles assessing lowland women sojourning at high altitude. Results: The literature search yielded 7,165 articles, 37 of which were ultimately included. The majority of publications included did not find women at increased risk for AMS or HACE. There was extremely limited sex-specific data on risk factors or treatment. Conclusions: There is a limited amount of data on female-specific findings regarding AMS and HACE, with most publications addressing only prevalence or incidence with regard to sex. As such, general prevention and treatment strategies for AMS and HACE should be used regardless of sex.

An Episode of "Third Person" Phenomenon Involving Somesthetic and Visual Hallucinations in a World-Class Extreme Altitude Climber.

Psychotic symptoms can occur at high altitude. However, most reports are in the mountaineering literature and lack a clear medical assessment and interpretation. Here we report an episode of isolated high-altitude psychosis. It consisted of a "third person" phenomenon involving 2 sensory modalities: somesthetic (felt presence) and visual (the light of 2 flashlights) hallucinations. This episode occurred in a highly experienced climber when he was at an altitude of approximately 7500 m while descending at dusk from the summit of Gasherbrum I (8068 m). The symptoms lasted approximately 3 h and had fully resolved on reaching high camp (7150 m). No other physical or mental symptoms were reported. In addition to hypoxia, a number of other risk factors could have contributed to the occurrence of psychosis in this climber. These included sleep deprivation, exhaustion, dehydration, electrolyte disturbance, reduced visibility, feeling of isolation, and perceived danger. The climber has participated in many extreme altitude expeditions, and neither before nor since this episode has the climber experienced psychotic symptoms.

Possibility for Children with Medical Complexities to Reach a 3000-m Peak: A Report of 2 Cases.

With the recent development of neonatal medicine, the number of children with medical complexities (CMCs) is increasing. Outdoor activities are important for their psychosocial development, and the principles of accessibility should be addressed. We report the experience of 2 CMCs' high-altitude mountaineering with the necessary support. The participants were a 3-y-old girl with cerebral palsy, symptomatic epilepsy, and a ventriculoperitoneal shunt (Child A) and a 6-y-old girl who underwent bilateral Glenn operations at 11 mo for hypoplastic left heart syndrome (Child B). The support staff consisted of 4 doctors, 1 nurse, 5 nonmedical staff , 3 members from a mountaineering association, and 2 people from an oxygen company. The climbing schedule was 2 days. On the first day, we took a bus to a hut at an altitude of 2450 m and stayed overnight to acclimatize to the altitude. On the second day, we took the beginner's route, which took 3 h to climb 500 m, and our team made an attempt on the summit. During the attempt, Child B panicked. Although her lung sounds did not raise suspicions of pulmonary edema, we decided to leave the mountain with her because her transcutaneous oxygen saturation decreased. Child A had no apparent health problems and made it to the summit. Although CMCs' alpine climbing requires careful planning and staffing considering the risk of high-altitude sickness, our case suggests the feasibility of such activities with CMCs as part of accessibility.

Prior Ambulatory Mild Coronavirus Disease 2019 Does Not Increase Risk of Acute Mountain Sickness.

Small, Elan, Caleb Phillips, William Bunzel, Lakota Cleaver, Nishant Joshi, Laurel Gardner, Rony Maharjan, and James Marvel. Prior ambulatory mild coronavirus disease 2019 does not increase risk of acute mountain sickness. High Alt Med Biol. 24:201-208, 2023. Background: Given its long-term morbidity, understanding how prior coronavirus disease 2019 (COVID-19) may affect acute mountain sickness (AMS) susceptibility is important for preascent risk stratification. The objective of this study was to examine if prior COVID-19 impacts risk of AMS. Materials and Methods: This was a prospective observational study conducted in Lobuje (4,940 m) and Manang (3,519 m), Nepal, from April to May 2022. AMS was defined by the 2018 Lake Louise Questionnaire criteria. COVID-19 severity was defined using the World Health Organization-developed criteria. Results: In the Lobuje cohort of 2,027, 46.2% of surveyed individuals reported history of COVID-19, with 25.7% AMS point-prevalence. There was no significant relationship between prior ambulatory mild COVID-19 and AMS (p = 0.6) or moderate AMS (p = 1.0). In the Manang cohort of 908, 42.8% reported history of COVID-19, with 14.7% AMS point-prevalence. There was no significant relationship between prior ambulatory mild COVID-19 and AMS (p = 0.3) or moderate AMS (p = 0.4). Average months since COVID-19 was 7.4 (interquartile range [IQR] 3-10) for Lobuje, 6.2 (IQR 3-6) for Manang. Both cohorts rarely exhibited moderate COVID-19 history. Conclusions: Prior ambulatory mild COVID-19 was not associated with increased risk of AMS and should not preclude high-altitude travel.

Prevalence of High-Altitude Polycythemia and Hyperuricemia and Risk Factors for Hyperuricemia in High-Altitude Immigrants.

Song Zhen, Anxin Zhang, Jie Luo, Guanghai Xiong, Haibo Peng, Rang Zhou, Yuanfeng Li, Hongqiang Xu, Zhen Li, Wei Zhao, and Haoxiang Zhang. Prevalence of high-altitude polycythemia and hyperuricemia and risk factors for hyperuricemia in high-altitude immigrants. High Alt Med Biol. 24:132-138, 2023. Background: Few studies have investigated the epidemiology of chronic mountain sickness (CMS) in high-altitude immigrants. This study evaluated the prevalence of polycythemia and hyperuricemia (HUA) and risk factors for HUA in high-altitude immigrants. Methods: A cross-sectional study was conducted with 7,070 immigrants 15-45 years of age living on the Tibetan Plateau between January and December 2021. Information from routine physical examinations was obtained from each participant. Binary logistic regression analysis was performed to determine the correlation of several risk factors for HUA. Results: The prevalence of high-altitude polycythemia (HAPC) and HUA was 25.8% (28.7% in males and 9.4% in females) and 54.2% (59.9% in males and 22.5% in females), respectively. The highest prevalence of HAPC in males and females was observed in participants 26-30 and 21-25 years of age, respectively. The highest prevalence of HUA in both males and females was observed in participants 26-30 years of age. Binary logistic regression analysis showed that age, sex, and hemoglobin (Hb) concentration were risk factors for HUA, among which age was a negative factor and male sex and Hb concentration were positive factors. Conclusions: Immigrants are more susceptible to HAPC and HUA. The high prevalence of CMS of immigrants may be associated with Hb concentration, age, and sex.

Association of Pre-existing Mental Health Conditions with Acute Mountain Sickness at Everest Base Camp.

Hüfner, Katharina, Fabio Caramazza, Evelyn R. Pircher Nöckler, Agnieszka E. Stawinoga, Paolo Fusar-Poli, Sanjeeb S. Bhandari, Buddha Basnyat, Monika Brodmann Maeder, Giacomo Strapazzon, Iztok Tomazin, Ken Zafren, Hermann Brugger, and Barbara Sperner-Unterweger. Association of pre-existing mental health conditions with acute mountain sickness at Everest Base Camp. High Alt Med Biol. 23:338-344, 2022. Background: Mental health disorders are common, but limited data are available regarding the number of people with a past medical history of psychiatric diagnoses going to high altitude (HA). It is also unknown whether mental health conditions are associated with an increased risk of acute mountain sickness (AMS). Methods: We analyzed data from a previous study at Everest Base Camp. Participants self-reported their past medical history and history of substance use and had a brief history taken by a physician. AMS was assessed using the self-reported 2018 Lake Louise AMS Score. Results: Eighty-five participants (66 men and 19 women, age 38 ± 9 years) were included. When questioned by a physician, 28 participants reported prior diagnoses or symptoms compatible with depression (23%), anxiety disorder (6%), post-traumatic stress disorder (1%), and psychosis/psychotic experiences (9%). The prevalence of psychiatric diagnoses in the past medical history was much lower in the self-reported data (2/85) compared to data obtained via physician assessment (28/85). Increased risks of AMS were associated with a past medical history of anxiety disorder (odds ratio [OR] 22.7; confidence interval [95% CI] 2.3-220.6; p < 0.001), depression (OR 3.6; 95% CI 1.2-11.2; p = 0.022), and recreational drug use ever (OR 7.3; 95% CI 1.5-35.5; p = 0.006). Conclusions: Many people who travel to HA have a past medical history of mental health conditions. These individuals have an increased risk of scoring positive for AMS on the Lake Louise Score compared with people without a history of mental health conditions.

Impact of moderate altitude on lung diseases and risk of high altitude illnesses.

A large world population resides at moderate altitudes. In the Valley of Mexico (2240 m above sea level) and for patients with respiratory diseases implies more hypoxemia and clinical deterioration, unless supplementary oxygen is prescribed or patients move to sea level. A group of individuals residing at 2500 or more meters above sea level may develop acute or chronic mountain disease but those conditions may develop at moderate altitudes although less frequently and in predisposed individuals. In the valley of México, at 2200 m above sea level, re-entry pulmonary edema has been reported. The frequency of other altituderelated diseases at moderate altitude, described in skiing resorts, remains to be known in visitors to Mexico City and other cities at similar or higher altitudes. Residents of moderate altitudes inhale deeply the city's air with all pollutants and require more often supplementary oxygen.

Brain structure and neurocognitive function in two professional mountaineers during 35 days of severe normobaric hypoxia.

BACKGROUND AND PURPOSE: Animal studies suggest that exposure to severe ambient hypoxia for several days may have beneficial long-term effects on neurodegenerative diseases. Because, the acute risks of exposing human beings to prolonged severe hypoxia on brain structure and function are uncertain, we conducted a pilot study in healthy persons. METHODS: We included two professional mountaineers (participants A and B) in a 35-day study comprising an acclimatization period and 14 consecutive days with oxygen concentrations between 8% and 8.8%. They underwent cerebral magnetic resonance imaging at seven time points and a cognitive test battery covering a spectrum of cognitive domains at 27 time points. We analysed blood neuron specific enolase and neurofilament light chain levels before, during, and after hypoxia. RESULTS: In hypoxia, white matter volumes increased (maximum: A, 4.3% ± 0.9%; B, 4.5% ± 1.9%) whilst gray matter volumes (A, -1.5% ± 0.8%; B, -2.5% ± 0.9%) and cerebrospinal fluid volumes (A, -2.7% ± 2.4%; B, -5.9% ± 8.2%) decreased. Furthermore, the number (A, 11-17; B, 26-126) and volumes (A, 140%; B, 285%) of white matter hyperintensities increased in hypoxia but had returned to baseline after a 3.5-month recovery phase. Diffusion weighted imaging of the white matter indicated cytotoxic edema formation. We did not observe changes in cognitive performance or biochemical brain injury markers. DISCUSSION: In highly selected healthy individuals, severe sustained normobaric hypoxia over 2 weeks elicited reversible changes in brain morphology without clinically relevant changes in cognitive function or brain injury markers. The finding may pave the way for future translational studies assessing the therapeutic potential of hypoxia in neurodegenerative diseases.

[Adaptation to altitude in respiratory diseases]. / Adaptation à l'altitude dans les maladies respiratoires.

The frequency of high-altitude sojourns (for work, leisure, air travel or during car/train journeys) justifies the question of their tolerance, especially in people with pre-existing respiratory disease. Reduced barometric pressure and abrupt variations in temperature and inhaled air density may be responsible for modifications affecting the respiratory system and, in fine, oxygenation. These modifications may compromise altitude tolerance, further worsen respiratory dysfunction and render physical exercise more difficult. In obstructive lung disease, altitude is associated with gas exchange impairment, increased ventilation at rest and during exercise and heightened pulmonary artery pressure through hypoxic vasoconstriction, all of which may worsen dyspnea and increase the risk of altitude intolerance (acute mountain sickness, AMS). The most severe patients require rigorous evaluation, and hypoxic testing can be proposed. People with mild to moderate intermittent asthma can plan high altitude sojourns, provided that they remain under control at night and during exercise, and follow an adequate action plan in case of exacerbation. Respiratory disease patients with pulmonary artery hypertension (PAH) and chemoreflex control abnormalities need to be identified as at risk of altitude intolerance.

Global REACH 2018: volume regulation in high-altitude Andeans with and without chronic mountain sickness.

The high-altitude maladaptation syndrome known as chronic mountain sickness (CMS) is characterized by polycythemia and is associated with proteinuria despite unaltered glomerular filtration rate. However, it remains unclear if indigenous highlanders with CMS have altered volume regulatory hormones. We assessed NH2-terminal pro-B-type natriuretic peptide (NT pro-BNP), plasma aldosterone concentration, plasma renin activity, kidney function (urinary microalbumin, glomerular filtration rate), blood volume, and estimated pulmonary artery systolic pressure (ePASP) in Andean males without (n = 14; age = 39 ± 11 yr) and with (n = 10; age = 40 ± 12 yr) CMS at 4,330 m (Cerro de Pasco, Peru). Plasma renin activity (non-CMS: 15.8 ± 7.9 ng/mL vs. CMS: 8.7 ± 5.4 ng/mL; P = 0.025) and plasma aldosterone concentration (non-CMS: 77.5 ± 35.5 pg/mL vs. CMS: 54.2 ± 28.9 pg/mL; P = 0.018) were lower in highlanders with CMS compared with non-CMS, whereas NT pro-BNP was not different between groups (non-CMS: 1394.9 ± 214.3 pg/mL vs. CMS: 1451.1 ± 327.8 pg/mL; P = 0.15). Highlanders had similar total blood volume (non-CMS: 90 ± 15 mL·kg-1 vs. CMS: 103 ± 18 mL·kg-1; P = 0.071), but Andeans with CMS had greater total red blood cell volume (non-CMS: 46 ± 10 mL·kg-1 vs. CMS: 66 ± 14 mL·kg-1; P < 0.01) and smaller plasma volume (non-CMS: 43 ± 7 mL·kg-1 vs. CMS: 35 ± 5 mL·kg-1; P = 0.03) compared with non-CMS. There were no differences in ePASP between groups (non-CMS: 32 ± 9 mmHg vs. CMS: 31 ± 8 mmHg; P = 0.6). A negative correlation was found between plasma renin activity and glomerular filtration rate in both groups (group: r = -0.66; P < 0.01; non-CMS: r = -0.60; P = 0.022; CMS: r = -0.63; P = 0.049). A smaller plasma volume in Andeans with CMS may indicate an additional CMS maladaptation to high altitude, causing potentially greater polycythemia and clinical symptoms.

Protection function of 18ß-glycyrrhetinic acid on rats with high-altitude pulmonary hypertension based on 1H NMR metabonomics technology.

18ß-Glycyrrhetinic acid (GA) is the triterpenoid aglycone component of glycyrrhizic acid, a natural product of traditional Chinese medicine, and has been proven to possess a variety of pharmacological effects. The protection function and the mechanism of GA on rats with high-altitude pulmonary hypertension (HAPH) are studied using proton nuclear magnetic resonance (1H NMR) metabonomics technology and biochemical analysis. An HAPH model is established, and 60 male rats are randomly divided into the following groups: Control(normal saline, 0.4 mL/100 g), model (normal saline, 0.4 mL/100 g), Nifedipine (nifedipine, 2.7 mg/kg), and high-, medium-, and low-dose GA groups (100, 50, and 25 mg/kg GA designated as GA.H, GA.M, and GA.L, respectively). Serum biochemical indicators of rats in each group are measured, and pathological changes in the pulmonary artery are observed. 1H NMR metabonomics technology is used for serum analysis. Results show that GA can significantly reduce pulmonary arterial pressure and malondialdehyde levels and increase the glutathione peroxidase and superoxide dismutase activities in HAPH rats. Pathological results show that GA can alleviate pulmonary artery injuries of HAPH rats. Metabolomics analytical findings show that GA can alleviate the metabolic disorder of HAPH rats through anti-oxidation and anti-inflammatory effects, improve their bodies' ability to resist hypoxia, and restore various metabolic pathways (energy metabolism, amino acid metabolism, and lipid metabolism). GA has potential therapeutic effects on HAPH rats, but its target needs to be further studied.

Effects of chronic intermittent hypobaric hypoxia on prostate-specific antigen (PSA) in Chilean miners.

OBJECTIVE: The aim was to determine the effects of chronic intermittent hypobaric hypoxia (CIHH) on prostate-specific antigen (PSA) levels in Chilean miners who work at different altitudes. METHODS: A cross-sectional study was conducted between April and July 2019. Miners from five mines (N=338) at different altitudes were evaluated. We recorded sociodemographic, working and altitude information. Haemoglobin oxygen saturation (SaO2) and haemoglobin (Hb) were measured in situ, while PSA and testosterone were analysed at a low level. Linear mixed-effect models were used to evaluate the association between PSA level and two CIHH exposures: composite CIHH (with four descriptors) and ChileStd-CIHH (CIHH Chilean standard; based on the Chilean technical guide for occupational exposure to CIHH). All models were adjusted by age, body mass index and day of the work the samples were taken. RESULTS: Highest and lowest PSA levels were found in mines ≥3000 m above sea level (mine 3: median=0.75, IQR=-0.45; mine 4: median=0.46, IQR=-0.35). In the multilevel models, the wider altitude difference between mining operation and camp showed lower PSA levels (model D: ßPSA=-0.93 ng/mL, ßlogPSA=-0.07, p<0001), adjusted for other CIHH descriptors, SaO2, Hb and testosterone. The descriptors of composite CIHH explained better PSA variations than ChileStd-CIHH (model D: marginal R2=0.090 vs model A: marginal R2=0.016). CONCLUSIONS: Occupational health regulations and high altitude medicine should consider these results as initial evidence on the inclusion of new descriptors for CIHH and the possible effect of this exposure on PSA levels in this male-dominated occupational sector.

[Chronic exposure to altitude. Clinical characteristics and diagnosis]. / Exposición crónica a la altura. Características clínicas y diagnóstico

Chronic exposure to altitude has been associated with hypobaric hypoxia in its inhabitants. Two entities have been associated with it, high altitude pulmonary hypertension and chronic mountain sickness. Its physiological and pulmonary circulation characteristics are described, as well as its clinical profile and diagnosis.

La exposición crónica a la altitud se ha asociado a hipoxia hipobárica en quienes la experimentan. Dos entidades se han asociado a la hipoxia hipobárica: la hipertensión pulmonar de la alta altitud y el mal de montaña crónico. Se describen sus características fisiológicas y de la circulación pulmonar, así como su perfil clínico y el diagnóstico.

Protective Effects from the Ischemic/Hypoxic Stress Induced by Labor in the High-Altitude Tibetan Placenta.

Labor and vaginal delivery cause acute ischemic/hypoxic insult to the placenta. Previous studies demonstrate that placentas from high altitude non-natives showed blunted responses to ischemic/hypoxic insult caused by labor and vaginal birth, and there were some differences in the ATP/ADP production ratio. We hypothesized that adapted highlanders would not have a stress response to the acute hypoxia/ischemia of labor. Tibetan laboring (n = 10) and non-laboring (n = 5) and European descendants laboring (n = 10) and non-laboring (n = 5) high-altitude placentas were analyzed using genome-wide expression array analysis. There was no evidence for ischemic/hypoxic stress in high-altitude Tibetan laboring as compared with non-laboring placentas, while there were differences in gene expression between laboring and non-laboring placentas from high-altitude European descendants. Our results provide evidence for adaptation to acute hypoxic ischemic insult caused by labor and vaginal birth in placentas in a high-altitude native Tibetan population.

High-altitude Illnesses and Air Travel: Pediatric Considerations.

Healthy children may present acute mountain sickness (AMS) within a few hours after arrival at high altitudes. In few cases, serious complications may occur, including high-altitude pulmonary edema and rarely high-altitude cerebral edema. Those with preexisting conditions especially involving hypoxia and pulmonary hypertension shall not risk travelling to high altitudes. Newborn from low altitude mothers may have prolonged time to complete postnatal adaptation. The number of children and adolescents traveling on commercial aircrafts is growing, and this poses a need for their treating physicians to be aware of the potential risks of hypoxia while air traveling.

Low Stroke Volume Index in Healthy Young Men Is Associated with the Incidence of Acute Mountain Sickness after an Ascent by Airplane: A Case-Control Study.

BACKGROUND: The aims of this study were to explore the characteristics of left ventricular (LV) functional changes in subjects with or without acute mountain sickness (AMS) and their associations with AMS incidence. METHODS: A total of 589 healthy men were enrolled and took a trip from Chengdu (500 m, above sea level (asl)) to Lhasa (3700 m, asl) by airplane. Basic characteristics, physiological data, and echocardiographic parameters were collected both at Chengdu and Lhasa, respectively. AMS was identified by the Lake Louise Questionnaire Score. RESULTS: The oxygen saturation (SpO2), end-systolic volume index, end-diastolic volume index (EDVi), stroke volume index (SVi), E-wave velocity, and E/A ratio were decreased, whereas the heart rate (HR), ejection fraction, cardiac index (CI), and A-wave velocity were increased at the third day after arrival, as evaluated by an oximeter and echocardiography. However, AMS patients showed higher HR and lower EDVi, SVi, CI, E-wave velocity, and E/A ratio than AMS-free subjects. Among them, SVi, which is mainly correlated with the changes of EDVi and altered LV filling pattern, was the most valuable factor associated with AMS incidence following receiver-operator characteristic curves and linear and Poisson regression. Compared with subjects in the highest SVi tertile, subjects in the middle SVi tertile showed higher multivariable Incidence Rate Ratios (IRR) for AMS with higher incidences of mild headache and gastrointestinal symptoms, whereas subjects in the lowest SVi tertile showed even higher multivariable IRR with higher incidences of all the symptoms. CONCLUSIONS: This relatively large-scale case-control study revealed that the reduction of SVi correlated with the altered LV filling pattern was associated with the incidence and clinical severity of AMS.