Low-altitude Group Research Articles

Effects of long-term high-altitude exposure on retinal and choroidal microcirculation

To quantify the effect of long-term high-altitude (HA) exposure on retinal and choroidal microcirculation and to relate these changes to high-altitude polycythemia (HAPC), as a proxy for etiopathogenesis of high-altitude related retinopathy (HAR). Fifty-one HAPC patients, 50 healthy HA residents, and 43 low altitude (LA) residents were recruited in this study. Optical coherence tomography angiography (OCTA) and enhanced depth imaging (EDI)-OCT images were analyzed. Retinal microvascular metrics included vessel density (VD), skeleton density (SD), fractal dimension (FD), and foveal avascular zone (FAZ). Choroidal microvascular metrics included subfoveal choroidal thickness (SFCT) and choroidal vascularity index (CVI). All metrics were calculated by ImageJ software and compared among HAPC group, healthy HA group, and LA group. In HAPC group, VD (30.62 ± 3.67%), SD (13.25 ± 1.64%), FD (1.79 ± 0.04), and the CVI (63.01 ± 1.42%) were significant lower and SFCT (403.25 ± 94.3μm) was significant thicker than healthy HA group (all P < 0.001). FAZ area was comparable between two groups (0.42 ± 0.1 vs. 0.4 ± 0.11 mm2, P = 0.411). However, these metrics were not different between healthy HA group and LA group (all P > 0.05) except for FD was lower in HA group (P < 0.001). Pearson's correlation analyses revealed HGB was negatively related with VD (r = - 0.562, P < 0.001) and positively related with SFCT (r = 0.505, P < 0.001) in healthy HA group; however, no associations between HGB and vascular metrics in HAPC group were detected (all P > 0.05). Long-term exposure to HA environment induces retinal and choroidal microcirculation disturbance in HAPC patients. However, these changes were not evident in healthy HA residents because of adaptation.

Effects of Chronic Hypoxic Environment on Cognitive Function and Neuroimaging Measures in a High-Altitude Population.

ObjectiveThis study aimed to investigate the effects of long-term hypoxic environment exposure on cognitive ability and neuroimaging characteristics in a highland population in China.MethodsHealth system workers in Maduo County (4,300 m above sea level) and Minhe County (1,700 m above sea level) were selected as research participants and divided into a high-altitude (HA) group and low-altitude (LA) group, respectively. Cognitive ability was assessed using the Montreal Cognitive Assessment (MoCA), Verbal Fluency Test (VFT), Symbol Digit Modalities Test (SDMT), Trail Making Test A and B (TMT), Digit Span Test (DST), and Rey Auditory Verbal Learning Test (RAVLT). All participants underwent a magnetic resonance imaging (MRI) scan, resting state functional MRI scan, and diffusion tensor imaging to clarify changes in regional gray matter (GM) volume, anisotropy index (FA), local consistency (ReHo), and low-frequency oscillation amplitude (ALFF).ResultsThe HA group had significantly lower MoCA, DST, VFT, RAVLT, and TMT scores compared to the control group. No significant differences were found in SDMT score. Furthermore, compared to the LA group, the HA group had significantly lower GM density of the left olfactory cortex, right medial orbital superior frontal gyrus, bilateral insula, left globus pallidus, and temporal lobe (left superior temporal gyrus temporal pole, bilateral middle temporal gyrus temporal pole, and right middle temporal gyrus). In terms of FA, compared with the LA group, the HA group had lower values for the corpus callosum, corpus callosum knee, bilateral radiative corona, and left internal capsule. The HA group had lower ALFF values of the left cerebellum, left putamen, left orbital inferior frontal gyrus, and left precuneus, but higher ALFF values of the left fusiform gyrus, bilateral inferior temporal gyrus, left orbital superior frontal gyrus and medial superior frontal gyrus, compared to the LA group. There was no significant group difference in ReHo values.ConclusionOur findings suggest that a chronic hypoxic environment can induce extensive cognitive impairment. Decreased GM density in multiple brain regions, damaged nerve fibers, and unbalanced neuronal activity intensity in different brain regions may be the structural and functional basis of cognitive impairment due to hypoxia.

High-altitude is associated with better short-term survival in critically ill COVID-19 patients admitted to the ICU.

Multiple studies have attempted to elucidate the relationship between chronic hypoxia and SARS-CoV-2 infection. It seems that high-altitude is associated with lower COVID-19 related mortality and incidence rates; nevertheless, all the data came from observational studies, being this the first one looking into prospectively collected clinical data from severely ill patients residing at two significantly different altitudes. A prospective cohort, a two-center study among COVID-19 confirmed adult patients admitted to a low (sea level) and high-altitude (2,850 m) ICU unit in Ecuador was conducted. Two hundred and thirty confirmed patients were enrolled from March 15th to July 15th, 2020. From 230 patients, 149 were men (64.8%) and 81 women (35.2%). The median age of all the patients was 60 years, and at least 105 (45.7%) of patients had at least one underlying comorbidity, including hypertension (33.5%), diabetes (16.5%), and chronic kidney failure (5.7%). The APACHE II scale (Score that estimates ICU mortality) at 72 hours was especially higher in the low altitude group with a median of 18 points (IQR: 9.5-24.0), compared to 9 points (IQR: 5.0-22.0) obtained in the high-altitude group. There is evidence of a difference in survival in favor of the high-altitude group (p = 0.006), the median survival being 39 days, compared to 21 days in the low altitude group. There has been a substantial improvement in survival amongst people admitted to the high-altitude ICU. Residing at high-altitudes was associated with improved survival, especially among patients with no comorbidities. COVID-19 patients admitted to the high-altitude ICU unit have improved severity-of-disease classification system scores at 72 hours.

Alteration of Behavioral Inhibitory Control in High-Altitude Immigrants.

Behavioral inhibitory control (BIC) acts as a key cognitive ability, which is essential for humans to withhold inappropriate behaviors. Meanwhile, many studies reported that long-term exposure to high altitude (HA) may affect cognitive ability. However, it is not clear whether long-term exposure to HAs may affect the BIC of an individual. To clarify the role of altitude in the behavioral control of adults and the underlying neural mechanism, we explored the BIC neural activity profiles of healthy immigrants from low-altitude (LA) regions to HA regions. Combining a two-choice oddball paradigm and electrophysiological techniques, this study monitored the N2 and P3 event-related components and neural oscillations across LA and HA groups. Results showed longer reaction times (RTs) for the HA group than the LA group. Relative to the LA group, lower N2 and P3 amplitudes were observed for the HA group. Significant positive correlations were also found between P3 amplitude and theta/delta band power across both groups. Importantly, lower theta/delta band powers were only observed for the HA group under the deviant condition. Collectively, these findings suggest that long-term exposure to HAs may attenuate BIC during the response inhibition stage and provide valuable insights into the neurocognitive implications of environmental altitude on BIC.

Features of the Course of Non-alcoholic Fatty Liver Disease in Experimental Animals at High Altitudes

Background: Nearly 25% of adults worldwide are affected by non-alcoholic fatty liver disease (NAFLD). taged changes in the liver from steatosis progress to non-alcoholic steatohepatitis (NASH) and its complicated forms such as fibrosis, cirrhosis, and hepatocellular carcinoma. There are very few data in the literature on the development of NAFLD in conditions of high altitude. There are no data on the state of pro- and anti-inflammatory cytokines in NAFLD in high altitude conditions. Thus, simulating NAFLD on animals in artificial highlands will help find answers to these questions.&#x0D; Aim: to study the features of the course of non-alcoholic fatty liver disease (NAFLD) in experimental animals in artificial high-mountain conditions.&#x0D; Material and methods: The study was carried out on 180 male Wistar rats. 7 groups of experimental animals were formed, which were divided into control and experimental groups. The rats of the control group were on a standard diet. Non-alcoholic fatty liver disease was modeled by keeping animals on a diet (Ackermann et al., 2005) rich in fructose and fat in low and high mountain conditions (in a pressure chamber 6000 m above sea level) for 35 and 70 days. In all groups of animals, the following was determined: the concentration of total bilirubin (TB), the activity of the enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), the level of total cholesterol (TC), low-density lipoprotein cholesterol (LDL), the total protein content in plasma (TP), pro- and anti-inflammatory cytokines.&#x0D; Results: In animals on a diet enriched with fructose and fat, it equally led to the inhibition of the synthetic function of the liver, both in high altitude and in low altitudes. Liver enzyme levels were uncertain. AST levels were high in all major groups, with a similar upward trend at 5 and 10 weeks on the fructose-fortified diet. The greatest shift was observed on the part of ALT in animals under conditions of hypobaric hypoxia, the growth of which was statistically significantly lower than in the low- altitude groups. The opposite picture was observed in pigment metabolism. Indicators of total cholesterol and LDL increased almost twofold in the main high- altitude groups, and were significantly higher than the indicators of low- altitude animals with p &lt;0.001. The activity of pro- and anti-inflammatory cytokines in the main group, when the animals were raised in the pressure chamber, statistically significantly increased after 5 weeks compared to the low-altitude group by more than 2 times and statistically significantly correlated with cytolysis syndromes, hypercholesterolemia and impaired synthetic function against the background of liver hypoergosis.&#x0D; Conclusion: Non-alcoholic fatty liver disease in animals on a special diet enriched with fructose under conditions of hypobaric hypoxia is characterized by deeper violations of pigment metabolism, pro- and anti-inflammatory cytokines and lipid spectrum with simultaneously statistically significant low alanine aminotransferase indices compared to low-altitude groups on an identical diet.

Hematological Parameters, Lipid Profile, and Cardiovascular Risk Analysis Among Genotype-Controlled Indigenous Kiwcha Men and Women Living at Low and High Altitudes.

Introduction: Human adaptation to high altitude is due to characteristic adjustments at every physiological level. Differences in lipid profile and cardiovascular risk factors in altitude dwellers have been previously explored. Nevertheless, there are no reports available on genotype-controlled matches among different altitude-adapted indigenous populations.Objective: To explore the possible differences in plasma lipid profile and cardiovascular risk among autochthonous Kiwcha people inhabitants of low and high-altitude locations.Methodology: A cross-sectional analysis of plasmatic lipid profiles and cardiovascular risk factors in lowland Kiwchas from Limoncocha (230 m) and high-altitude Kiwchas from Oyacachi (3,800 m).Results: In the low altitude group, 66% were women (n = 78) and 34% (n = 40) were men, whereas in the high altitude group, 59% (n = 56) were women and 41% (n = 41%) were men. We found the proportion of overweight and obese individuals to be higher among low altitude dwellers (p < 0.05). Red blood cells (RBCs), hemoglobin concentration, and SpO2% were higher among high altitude dwellers and the erythrocyte size was found to be smaller at high altitude. The group located at low altitude also showed lower levels of plasma cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL), but most of these differences are not influenced by gender or elevation.Conclusions: Living at an altitude elicits well-known adaptive physiological changes such as erythrocyte count, hemoglobin concentration, hematocrit level, and serum glucose level. We also report clinical differences in the plasma lipid profile, with higher levels of cholesterol, HDL, and LDL in inhabitants of the Andes Mountain vs. their Amazonian basin peers. Despite this, we did not find significant differences in cardiovascular risk.

Clinical and Immunological Characteristics of Patients With Adenovirus Infection at Different Altitude Areas in Tibet, China.

BackgroundThe severities of human adenovirus (HAdV) infection are diverse in different areas of Tibet, China, where a large altitude span emerges. Serious consequences may be caused by medical staff if the clinical stages and immunological conditions of patients in high-altitude areas are misjudged. However, the clinical symptoms, immunological characteristics, and environmental factors of HAdV infection patients at different altitude areas have not been well described.MethodsIn this retrospective, multicenter cohort study, we analyzed the data of patients who were confirmed HAdV infection by PCR tests in the General Hospital of Tibet Military Command or CDC (the Center for Disease Control and Prevention) of Tibet Military Command from January 1, 2019, to December 31, 2020. Demographic, clinical, laboratory, radiological, and epidemiological data were collected from medical records system and compared among different altitude areas. The inflammatory cytokines as well as the subsets of monocytes and regulatory T cells of patients were also obtained and analyzed in this study.ResultsSix hundred eighty-six patients had been identified by laboratory-confirmed HAdV infection, including the low-altitude group (n = 62), medium-altitude group (n = 206), high-altitude group (n = 230), and ultra-high-altitude group (n = 188). Referring to the environmental factors regression analysis, altitude and relative humidity were tightly associated with the number of infected patients (P < 0.01). A higher incidence rate of general pneumonia (45.7%) or severe pneumonia (8.0%) occurred in the ultra-high-altitude group (P < 0.05). The incubation period, serial interval, course of the disease, and PCR-positive duration were prolonged to various extents compared with the low-altitude group (P < 0.05). Different from those in low-altitude areas, the levels of IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, TNF-α, TNF-β, and VEGF in the plasma of the ultra-high-altitude group were increased (P < 0.05), while the proportion of non-classical monocytes and regulatory T cells was decreased (P < 0.05).ConclusionsThe findings of this research indicated that patients with HAdV infection in high-altitude areas had severe clinical symptoms and a prolonged course of disease. During clinical works, much more attention should be paid to observe the changes in their immunological conditions. Quarantine of patients in high-altitude areas should be appropriately extended to block virus shedding.

Stroke-Related Mortality at Different Altitudes: A 17-Year Nationwide Population-Based Analysis From Ecuador.

Introduction: Worldwide, more than 5.7% of the population reside above 1,500 m of elevation. It has been hypothesized that acute short-term hypoxia exposure could increase the risk of developing a stroke. Studies assessing the effect of altitude on stroke have provided conflicting results, some analyses suggest that long-term chronic exposure could be associated with reduced mortality and lower stroke incidence rates.Methods: An ecological analysis of all stroke hospital admissions, mortality rates, and disability-adjusted life years in Ecuador was performed from 2001 to 2017. The cases and population at risk were categorized in low (<1,500 m), moderate (1,500–2,500 m), high (2,500–3,500 m), and very high altitude (3,500–5,500 m) according to the place of residence. The derived crude and direct standardized age-sex adjusted mortality and hospital admission rates were calculated.Results: A total of 38,201 deaths and 75,893 stroke-related hospital admissions were reported. High altitude populations (HAP) had lower stroke mortality in men [OR: 0.91 (0.88–0.95)] and women [OR: 0.83 (0.79–0.86)]. In addition, HAP had a significant lower risk of getting admitted to the hospital when compared with the low altitude group in men [OR: 0.55 (CI 95% 0.54–0.56)] and women [OR: 0.65 (CI 95% 0.64–0.66)].Conclusion: This is the first epidemiological study that aims to elucidate the association between stroke and altitude using four different elevation ranges. Our findings suggest that living at higher elevations offers a reduction or the risk of dying due to stroke as well as a reduction in the probability of being admitted to the hospital. Nevertheless, this protective factor has a stronger effect between 2,000 and 3,500 m.

Dynamics of Pro- and Anti-inflammatory Cytokines in Experimental Animals with Non-alcoholic Fatty Liver Disease Under Conditions of Hypobaric Hypoxia

AIM: The aim of the study was to study the level of pro- and anti-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α), and interleukin 4 (IL-4), on a model of non-alcoholic fatty liver disease (NAFLD) in experimental animals under conditions of low mountains and hypobaric hypoxia. METHODS: The study was carried out on 180 male Wistar rats, which were divided into control and experimental groups. The rats of the control group were on a standard diet. NAFLD was modeled by keeping animals on a diet (Ackermann et al., 2005) rich in fructose and fat in conditions of low mountains and hypobaric hypoxia (in a pressure chamber 6000 m above sea level) for 35 and 70 days. Total cholesterol (TC) and lipid spectrum, pro- and anti-inflammatory cytokines were determined in all groups of animals. RESULTS: The activity of pro- and anti-inflammatory cytokines in the main group during the rise of animals in the pressure chamber increased statistically significantly on the 35th day in comparison with the low-altitude group by more than 2 times, and on the 70th day of staying at the high-altitude did not have convincing differences from the low-altitude group. The cytokine index (TNF-α/IL-4) of animals in conditions of hypobaric hypoxia on a fructose enriched diet increased by more than 1.5 times after 5 weeks, staying at an altitude for 10 weeks led to a decrease of TNF-α/IL-4 in relation to the low-mountain group, in which the opposite picture was observed - a tendency towards an increase in TNF-α/IL-4. IL-4 and TNF-α _levels were statistically significantly correlated with lipid metabolism disorders. CONCLUSION: NAFLD in animals on a special diet enriched with fructose under conditions of hypobaric hypoxia leads to deeper disturbances in the system of pro- and anti-inflammatory cytokines and the lipid spectrum.

Effects of altitude on circulating endothelial progenitor cells and hypoxia-inducible factor-1α in patients with type 2 diabetes

Objective: To compare the changes in the number of circulating endothelial progenitor cells and hypoxia-inducible factors in patients with type 2 diabetes at different altitudes, and to provide a basis for the research and treatment of type 2 diabetes vascular complications. Methods: Selected Type 2 diabetes patients who were diagnosed in a low altitude area of 386 m (Xianyang City) and a high altitude area of 1 520 m (Lanzhou) (25 persons/29 persons) and healthy persons (20 persons/20 persons) were selected. An automatic biochemical analyzer was used to detect the indexes of blood lipids, blood glucose, and glycosylated hemoglobin of the two groups of people, and the concentration of Hypoxia inducible factor-1α (HIF-1α) was detected by enzyme-linked immunosorbent assay (ELISA). The number of circulating endothelial progenitor cells (EPCs) in peripheral blood was determined by a cytometer. Results: No matter in low or high altitude areas, the number of circulating EPCs in the diabetes group was lower than that in the healthy group (P＜0.01). The levels of body mass index (BMI), waist to hip ratio (WHR), triglyceride (TG), fasting blood glucose (FBG) and glycosylated hemoglobin (HbAlc) were increased (P＜0.05). Compared with the low-altitude group, the expression levels of HIF-1α in diabetic patients at high-altitude and healthy people were increased significantly (P＜0.05), while the number of circulating EPCs was decreased significantly (P＜0.05), and the number of circulating EPCs in healthy people or the patients with type 2 diabetes without vascular complications was higher than that of patients with type 2 diabetes with vascular complications (P＜0.05). Conclusion: With the increase in altitude, the expression level of HIF-1α in type 2 diabetes mellitus(T2DM)patients is increased, and the number of circulating EPCs is decreased, which is closely related to the degree of vascular disease. Therefore, it is possible through transplantation of EPCs for high altitude T2DM patients to achieve the prevention and improvement of diabetic vascular complications.

Long-Term High-Altitude Exposure Does Not Increase the Incidence of Atrial Fibrillation Associated with Organic Heart Diseases.

Wang, Man, Mengxue Liu, Jia Huang, Dan Fan, Shengzhong Liu, Tao Yu, Keli Huang, Xinchuan Wei, and Qian Lei. Long-term high-altitude exposure does not increase the incidence of atrial fibrillation associated with organic heart diseases. High Alt Med Biol. 22:285-292, 2021. Background: Atrial fibrillation (AF) is one of the most common arrhythmias and is associated with several complications following cardiac surgery. However, the differences in the incidence of AF associated with organic heart diseases between highland and lowland populations have not been comprehensively studied. Methods: In this retrospective study, a total of 2,316 highland and lowland patients who underwent cardiac surgery between January 2013 and December 2018 in a single center were enrolled. According to the altitude of residence, patients were divided into high-altitude (>1,500 m) and low-altitude (<1,500 m) groups. A propensity score matching analysis was performed to estimate the association of lifetime high-altitude exposure with AF. Results: Among the enrolled patients, 239 (10.9%) were from a high-altitude plateau, while 1,946 (89.1%) were from a low-altitude area. There were statistical differences in age, gender, European System for Cardiac Operative Risk Evaluation, and other factors, between the two groups (p < 0.05). According to the propensity score, 237 patients in the high-altitude group were successfully matched to 237 patients in the low-altitude group without significant difference in baseline data (p > 0.05). Among the matched patients, 125 patients (26.4%) suffered from AF, with 66 (27.8%) in the high-altitude group and 59 (24.9%) in the low-altitude group. The incidence of AF was statistically similar between the two groups and not significantly influenced by long-term high-altitude exposure (odds ratio 1.07; 95% confidence interval 0.71-1.60, p > 0.05). Conclusion: Long-term high-altitude exposure did not significantly increase the occurrence of AF in patients with organic heart diseases. Clinical Trial No. ChiCTR1900028612.

Repeated remote ischaemic preconditioning can prevent acute mountain sickness after rapid ascent to a high altitude

ABSTRACT Background This study assessed the effectiveness of 4 different repeated remote ischaemic preconditioning (RIPC) protocols varying in duration and frequency for preventing acute mountain sickness (AMS) after rapid ascent to high altitude. Methods In a randomized but not blinded design, participants were assigned to receive either of the four RIPC treatments at low altitude (Group A, once daily for 1 week; Group B, twice daily for 1 week; Group C, once daily for 4 weeks; and Group D, twice daily for 4 weeks) or control (no specific sham treatment). Participants were then flown to a high altitude (3650 m). The primary outcome was the incidence and severity of AMS evaluated by the Lake Louise score (LLS) after arrival; vital signs were collected simultaneously. Results A total of 250 participants (50 per group; mean age 38.56 ± 0.76 years) were included. The overall AMS incidence was 26.4%. A total of 20 AMS cases (40%) occurred in the control group, 15 cases (30%) both in the RIPC A and RIPC B groups (RR 1.3; 95%CI 0.8-2.3; χ2 = 1.099; p = 0.29), and 8 cases (16%) both in the RIPC C and D groups (RR 2.5; 95%CI 1.2 - 5.2; χ2 = 7.143, p < 0.01), with significantly lower LLSs in the RIPC C and D groups (F = 6.51, p < 0.001). The scores of gastrointestinal symptoms (F = 7.42, p < 0.001) and dizziness (F = 9.82, p < 0.001) but not headache (F = 0.60, p > 0.05) were lower in the RIPC groups compared to control. The blood oxygen saturation level (SpO2) decreased less in the RIPC B, C and D groups compared to control after arrival at a high altitude (F = 11.42, p < 0.001). The number of RIPC treatments received was moderately correlated with SpO2 (R = 0.38, p < 0.001), and SpO2 was moderately inversely correlated with the LLS (R = –0.48, p < 0.001). Conclusion This study demonstrated that a four-week RIPC intervention but not a one-week regimen reduced AMS incidence and severity; however, a placebo effect might have contributed to these results.

Radial growth of Larix sibirica was more sensitive to climate at low than high altitudes in the Altai Mountains, China

Considering climate change, there is no consensus on the impact of global warming on forest growth. Therefore, it is crucial to investigate the effects of climate change on tree radial growth. However, in arid eastern central Asia, the large-spatial scale radial growth-climate relationship remains poorly understood. In this study, we collected radial growth data from 13 Siberian larch (Larix sibirica) plots along an altitudinal gradient (1100–2200 m a.s.l.) in the Altai Mountains, China. Principal component analysis (PCA), bootstrapped correlation, and linear regression were conducted to detect and quantify the effects of climatic factors on radial growth and to reveal the spatial variation in the radial growth-climate relationship. Results showed that chronologies were clustered into low- and high-altitude groups. In the low-altitude group, the self-calibrating Palmer Drought Severity Index (scPDSI) in current April showed a strong positive impact on radial growth, while the previous September mean temperature and diurnal temperature range in previous July both significantly negatively affected radial growth. These three climate variables explained 63% of radial growth variance. Among them, the scPDSI, with a relative importance of 63%, was the primary limiting factor. In the high-altitude group, the current January maximum temperature and previous July precipitation were significantly negatively correlated with radial growth, while the June minimum temperature was significantly positively correlated with radial growth. These three climatic factors together contributed to 38% variance in radial growth. Furthermore, the plot-specific relationship between climate variables and radial growth varied significantly with different altitudes. As the climate becomes wetting and warming in the Altai Mountains, our result suggests that the radial growth might benefit in an altitude between 1800 and 1900 m a.s.l., where temperature and precipitation were both positively correlated with radial growth. These findings will provide a basis for sustainable forest management under global climate change.

Effects of long-term high-altitude exposure on fibrinolytic system

ABSTRACT Objective High altitude (HA), with the main feature of hypobaric hypoxia, is an independent risk factor for thrombosis. However, little is known on the alterations of fibrinolytic system in adaptation to HA. In this study, we investigated changes of fibrinolytic system parameters between individuals permanently living at HA and low altitude (LA) regions, and provided data for further studies on HA-induced thrombotic disease. Material and methods A total of 226 eligible participants, including 103 LA participants, 100 healthy HA subjects and 23 high altitude polycythemia (HAPC) patients, were recruited in this study. Six fibrinolytic parameters, i.e. fibrinogen (Fbg), D-dimer (DDi), antithrombin III (AT-III), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) and plasminogen (PLG) were analyzed respectively. PAI-1 and tPA were performed by using bio-immuno-assays and an automated coagulation analyzer was used to conduct Fbg, DDi, AT-III and PLG tests. Results Plasma levels of Fbg, DDi, PAI-1 and PLG were significantly higher in healthy HA group than in LA group (all p < 0.05), whereas tPA was significantly lower in healthy HA group. No significant difference in AT-III was observed between healthy HA and LA groups (p > 0.05). All these fibrinolytic parameters showed no significant distinctions between healthy HA subjects and HAPC patients (all p > 0.05). HGB showed no relationship with fibrinolytic parameters in HA cohort. Conclusion This study demonstrates that HA environment has a significant effect on fibrinolytic system and provides a foundation for further studies on HA hypobaric hypoxia-induced thrombotic disease.

Effect of High-Altitude Environment on Driving Safety: A Study on Drivers’ Mental Workload, Situation Awareness, and Driving Behaviour

This study aims to analyze the effect of high-altitude environment on drivers’ mental workload (MW), situation awareness (SA), and driving behaviour (DB), and to explore the relationship among those driving performances. Based on a survey, the data of 356 lowlanders engaging in driving activities at Tibetan Plateau (high-altitude group) and 341 lowlanders engaging in driving activities at low altitudes (low-altitude group) were compared and analyzed. The results suggest that the differences between the two groups are noteworthy. Mental workload of high-altitude group is significantly higher than that of low-altitude group, and their situation awareness is lower significantly. The possibility of risky driving behaviours for high-altitude group, especially aggressive violations, is higher. For the high-altitude group, the increase of mental workload can lead to an increase on aggressive violations, and the situation understanding plays a full mediating effect between mental workload and aggressive violations. Measures aiming at the improvement of situation awareness and the reduction of mental workload can effectively reduce the driving risk from high-altitude environment for lowlanders.

Effect of altitude on mortality of end-stage renal disease patients on hemodialysis in Peru.

BackgroundIn Latin America, the prevalence of end-stage kidney disease (ESKD) has risen tremendously during the last decade. Previous studies have suggested that receiving dialysis at high altitude confers mortality benefits; however, this effect has not been demonstrated at >2000 m above sea level (masl) or in developing countries.MethodsThis historical cohort study analyzed medical records from six Peruvian hemodialysis (HD) centers located at altitudes ranging from 44 to 3827 masl. Adult ESKD patients who started maintenance HD between 2000 and 2010 were included. Patients were classified into two strata based on the elevation above sea level of their city of residence: low altitude (<2000 masl) and high altitude (≥2000 masl). Death from any cause was collected from national registries and Cox proportional hazards models were built.ResultsA total of 720 patients were enrolled and 163 (22.6%) resided at high altitude. The low-altitude group was significantly younger, more likely to have diabetes or glomerulonephritis as the cause of ESKD and higher hemoglobin. The all-cause mortality rate was 84.3 per 1000 person-years. In the unadjusted Cox model, no mortality difference was found between the high- and low-altitude groups {hazard ratio [HR] 1.20 [95% confidence interval (CI) 0.89–1.62]}. After multivariable adjustment, receiving HD at high altitude was not significantly associated with higher mortality, but those with diabetes as the cause of ESKD had significantly higher mortality [HR 2.50 (95% CI 1.36–4.59)].ConclusionsIn Peru, patients receiving HD at high altitudes do not have mortality benefits.

Impact of Altitude-based Hemoglobin Modification on Pediatric Iron Deficiency Anemia Screening

To determine if additional children attending primary care clinics in moderate-altitude areas would screen positive for anemia if the hemoglobin cutoff were modified for altitude. This cross-sectional study evaluated children aged 11-19months of age who had a screening hemoglobin conducted between January 2011 and December 2017 at 4 moderate-altitude (1726-2212m) and 8 low-altitude (1-20m) US military clinics. The primary outcome was anemia prevalence (hemoglobin <11g/dL) in moderate-altitude and low-altitude groups, before and after applying the current World Health Organization model for altitude-based hemoglobin modification. Groups were compared with prevalence ORs adjusted for age, sex, weight-for-length percentile, and parental military rank, and the false-negative proportion was calculated for children with anemia at moderate altitude. Before altitude modification, anemia prevalence was 4.4% in the moderate-altitude group (n=1488) and 16.8% in the low-altitude group (n=7090) (prevalence OR, 0.23; 95% CI, 0.17-0.29). After applying the World Health Organization model, anemia prevalence in the moderate-altitude group increased to 14.7% (prevalence OR, 0.82; 95% CI, 0.70-0.97). Nonapplication of the model at moderate altitude resulted in a false-negative proportion of 0.70 (95% CI, 0.63-0.76). Nonuse of the World Health Organization altitude-based modification model for hemoglobin may result in a large percentage of US children with anemia at moderate altitude screening falsely negative for anemia. Although ancestry disparities in altitude acclimatization may limit universal application of the current World Health Organization model, the existing standard of care may leave children at moderate altitude at risk for complications from iron deficiency anemia.

High-Altitude Is Associated with Better Short-Term Survival in Critically Ill COVID-19 Patients Admitted to the ICU

Background: The novel human coronavirus, SARS-CoV-2, has affected at least 218 countries worldwide. Some geographical and environmental factors are positively associated with a better or worse prognosis concerning COVID-19 disease and with lower or higher SARS-CoV-2 transmission. High altitude exposure has been associated with lower SARS-CoV-2 attack rates; nevertheless, the role of chronic high-altitude exposure on the clinical outcome of critically ill COVID-19 patients has not been studied.Objective: To compare the clinical course and outcomes of critically ill patients with COVID-19 hospitalized in two intensive care units (ICU) located at low and high altitude.Exposure and Outcome: To explore the effect of two different elevations (10 m vs 2,850 m above sea level) on COVID-19 clinical outcome and survival.Methods: A prospective cohort, two-center study in confirmed COVID-19 adult patients admitted to a low altitude (Sea level) and high altitude (2,850 m) ICU units in Ecuador was conducted. Two hundred and thirty confirmed COVID-19 patients were enrolled from March 15th to July 15th, 2020. Sociodemographic, clinical, laboratory and imaging parameters including supportive therapies, pharmacological treatments and medical complications were reported and compared between the low and high-altitude groups.Results: The median age of all the patients was 60 years, 64.8% were men and 35.2% were women. A total of 105 (45.7%) patients had at least one underlying comorbidity, the most frequent being chronic diseases, such as hypertension (33.5%), diabetes (16.5%), and chronic kidney failure (5.7%). The APACHE II scale at 72 hours was especially higher in the low-altitude group with a median of 18 points (IQR: 9.5-24.0), compared to 9 points (IQR: 5.0-22.0) obtained in the group of high altitude. There is evidence of a difference in survival in favor of the high-altitude group (p = 0.006), the median survival being 39 days, compared to 21 days in the low altitude group. Conclusion: There has been a substantial improvement in survival amongst people admitted to the high-altitude critical care unit. Low altitude living was associated with improved survival, especially among patients with no comorbidities. COVID-19 patients admitted to the high-altitude ICU unit have improved severity-of-disease classification system scores at 72 hours and reported better respiratory and ventilatory profiles than the low altitude group.Funding Statement: This work did not receive a formal grant: however, it received financial support associated with the publication fee from the University of the Americas in Quito, Ecuador.Declaration of Interests: The authors have no conflict of interest to declare.Ethics Approval Statement: This work was approved by the hospital's internal bioethical review committee (ID: IESS-HG-SQ-CIE-2020-2656-M).

Longitudinal observation of intraocular pressure variations with acute altitude changes.

BACKGROUNDHigher intraocular pressure (IOP) is a major risk factor for developing glaucoma, and the leading cause of irreversible blindness worldwide. High altitude (HA) may be involved in IOP, but the reported results were conflicting. Ascent to HA directly by plane from low altitude regions is an acute, effortless exposure. However, the effects of such exposure to different altitudes on IOP have rarely been reported.AIMTo investigate changes in IOP after rapid effortless exposure to HA in stages and compare it with systemic parameters.METHODSFifty-eight healthy subjects (116 eyes) were divided into three groups: 17 low-altitude (LA) residents [44 m above sea level (ASL)], 22 HA residents (2261 m ASL) and 19 very HA (VHA) residents (3750 m ASL). The LA group flew to HA first. Three days later, they flew with the HA group to VHA where both groups stayed for 2 d. Then, the LA group flew back to HA and stayed for 1 d before flying back to 44 m. IOP, oxygen saturation (SpO2) and pulse rate were measured. The linear mixed model was used to compare repeated measurements.RESULTSIOP in the LA group significantly decreased from 18.41 ± 2.40 mmHg at 44 m to 13.60 ± 3.68 mmHg at 2261 m ASL (P < 0.001), and then to 11.85 ± 2.48 mmHg at 3750 m ASL (P = 0.036 compared to IOP at 2261 m ASL) and partially recovered to 13.47 ± 2.57 mmHg upon return to 44 m. IOP in the LA group at HA and VHA was comparable to that in the local residents (12.2 ± 2.4 mmHg for HA,11.5 ± 1.8 mmHg for VHA). IOP was positively associated with SpO2.CONCLUSIONIOP in the LA group gradually reduced as altitude elevated in stages and became comparable to IOP in local residents. Hypoxia may be associated with IOP, which deserves further study.

Clinical characteristics of acute pulmonary embolism at different altitudes in plateau areas

Objective: To analyze the clinical characteristics of pulmonary embolism patients from different altitudes in plateau areas. Methods: A retrospective cross-sectional study was used to analyze the patients with acute pulmonary embolism diagnosed definitely by pulmonary angiography or pulmonary artery CT angiography admitted to Tibet Autonomous Region People's Hospital from August 2014 to December 2018. The subjects were divided into 3 groups according to the altitude of long-term residence before onset, i.e. low-altitude group (group 1, 2 700 m ≤ altitude ≤3 700 m, n=44), medium-altitude group (group 2, 3 700 m<altitude ≤4 000 m, n=30) and high altitude group (group 3, 4 000 m<altitude ≤4 800 m, n=32). The clinical data, auxiliary examination and risk stratification of pulmonary embolism patients at different altitudes were compared and analyzed. Results: The incidence of chest pain, dyspnea and lower limb fracture in the three groups were statistically significant (P<0.05). The incidence of chest pain in group 2 (70%) was higher than that in group 1(40.9%), and dyspnea in group 3 (93.8%) was higher than that in group 2(66.7%), while lower limb fracture in group 3 (43.8%) was higher than that in group 1(15.9%). The differences in arterial oxygen partial pressure, hemoglobin and D-dimer among the three groups were statistically significant (P<0.05). The arterial oxygen partial pressure [52(43.5-63.5)mmHg] in group 3 was lower than that in group 1 [60 (53.25-73) mmHg]. The hemoglobin (163.1±43.3 g/L) and D-dimer [5.6(3.7-12.6)mg/L] in group 3 were higher than those in group 1 [143.5±38.9 g/L and 3.8(2.0-7.5)mg/L respectively]. The risk stratification of the three groups of patients was moderate or low, and there was no statistical difference among the three groups. In patients with the same low-risk grade, the D-dimer in group 3 was higher than that in group 1 [5.8(4.2-14.8)mg/L and 3.6(2.3-5.8)mg/L respectively, P<0.05]. In patients with the same moderate risk level, the arterial oxygen partial pressure in group 3 was lower than that in group 1 [47.0(36.0-58.0)mmHg and 59.5(52.3-68.5)mmHg, respectively, P<0.05]. Conclusion: There was no difference in the risk stratification of pulmonary embolism from different altitudes in plateau areas, but patients who lived at higher altitudes for a long time showed more significant hypoxemia and increased hemoglobin and D-dimer levels.