Análisis de los efectos globales que ocasiona la hipoxia hipobárica crónica sobre el estado físico-emocional de los pobladores que residen en altitudes mayores a los 2,500 msnm

Programa de Doctorat en BiomedicinaANTECEDENTES: A nivel planetario, al menos 200 millones de personas a nivel mundial residen en poblaciones ubicadas a grandes alturas. Vivir o visitar regiones montañosas puede provocar cambios fisiológicos significativos entre quienes visitan estos lugares durante cortos periodos de tiempo o provocar modificaciones adaptativas más crónicas entre quienes residen allí durante varias generaciones. Los seres humanos dependen de la presencia, disponibilidad y utilización de oxígeno para funcionar correctamente y mantener la homeostasis fisiológica alrededor de la respiración. En condiciones de hipoxia, los mecanismos adaptativos a largo plazo o compensatorios a corto plazo generan alteraciones genéticas, anatómicas, fisiológicas y, en algunos casos, patológicas entre los seres humanos. OBJETIVOS: El objetivo de nuestro estudio ha sido doble: desde un punto de vista más general, el de estudiar el impacto epidemiológico que representa el vivir por encima de los 2.500 m sobre el nivel del mar, y, más detalladamente, estudiar las diferencias fisiológicas más evidentes entre dos poblaciones indígenas, genotípicamente idénticas que residen a baja y gran altura. RESULTADOS: a) Diferencias antropométricas Nuestra tesis ha demostrado que las mujeres que residen a bajas alturas tienden a presentar tallas más cortas y mayor peso que sus pares de las grandes alturas, aunque estas diferencias no fueron estadísticamente significativas (p = 0,333). A su vez, los hombres que residen a grandes alturas son más bajos de talla que sus homólogos que viven a bajas alturas, siendo estos resultados estadísticamente significativos (p = 0,019). En relación con la composición corporal, las mujeres de las alturas tienen un porcentaje menor de músculo corporal (-24,8%), mientras que los hombres de la misma región tienen un porcentaje de masa corporal muscular significativamente mayor (+ 13,5%) que sus homólogos de bajas alturas. El porcentaje de grasa corporal fue menor entre las mujeres de las bajas alturas (-15,5%), mientras que entre los hombres no logramos encontrar diferencias estadísticamente significativas. b) Diferencias hematológicas, de perfil lipídico y de riesgo cardiovascular Al comparar estos parámetros, nuestros resultados nos demuestran que la proporción de individuos con sobrepeso y obesidad fue mayor entre los habitantes de las bajas alturas (p <0,05). A la vez, el número de glóbulos rojos (RBC), la concentración de hemoglobina y la fueron significativamente más altos entre los habitantes de las grandes alturas, mientras que la saturación de oxigeno arterial (SpO2%) y el tamaño de los glóbulos rojos resultaron ser menores entre pobladores de las grandes alturas. Por otro lado, el grupo viviendo cerca del nivel del mar, mostró niveles más bajos de colesterol plasmático, lipoproteínas de baja densidad (LDL) y lipoproteínas de alta densidad (HDL). c) Optimismo y autopercepción Los habitantes de las zonas altas presentaron puntuaciones más bajas en todas las dimensiones estudiadas dentro de la encuesta de salud SF-36. Las diferencias estadísticamente significativas se encontraron dentro de la esfera de vitalidad (p = 0,005), Salud Mental (p = 0,002) y funcionamiento social (p = 0,005). En todos los casos, los participantes que vivían a bajas alturas puntuaban más que los que vivían a grandes alturas. Por otro lado, las mujeres de la amazonia, que residen a baja altura, resultaron ser más optimistas que sus homólogas de las grandes alturas. d) Función pulmonar y parámetros ventilatorios Los habitantes de Oyacachi (3,800 m) mostraron tener valores predictivos mayores que los habitantes de Limoncocha (230 m). Por ejemplo, la capacidad vital forzada (CVF) y el volumen espiratorio forzado en un segundo (VEF1) fueron significativamente mayores entre los habitantes de las tierras altas que la de sus pares amazónicos (valor p < 0,001). El índice de Tiffeneau (VEF1/CVF) fue significativamente mayor entre los habitantes de las bajas alturas que entre los que residen a mayor elevación, siendo esto evidente tanto en hombres como en mujeres. CONCLUSIONES: Vivir a grandes alturas se asocia a cambios fisiológicos adaptativos bien conocidos y descritos como son el recuento de eritrocitos, la concentración de hemoglobina o el nivel de hematocrito. Nuestros resultados también demuestran que existen diferencias clínicas en el perfil lipídico plasmático, teniendo niveles más altos de colesterol, HDL y LDL entre los habitantes de las grandes alturas. Las diferencias antropométricas varían según el sexo y la edad. Nuestros hallazgos sugieren que la población que reside por sobre los 3,800 m es en general más ligera de peso y más baja en talla que la de sus pares de bajas alturas. Los hombres que residen a grandes alturas tienen cuerpos con mayores porcentajes de masa muscular que sus homólogos de las tierras bajas, pero en términos de edad corporal, los pobladores de las alturas resultaron ser mayores que los de las bajas alturas. Los habitantes de las grandes alturas tuvieron mayor capacidad pulmonar que la de sus pares de las bajas alturas. Al analizar los patrones espirométricos obtenidos en estas poblaciones, resultó evidente que las mayores capacidades pulmonares están probablemente relacionadas con pulmones más grandes, lo que mejora la oxigenación sistémica a pesar de la baja disponibilidad de oxígeno.BACKGROUND: On a planetary level, at least 200 million people of the world's population resides at high altitude. Living or visiting mountainous regions can lead to significant physiological changes among those visiting these places for short periods of time or lead to more chronic adaptive modifications among those who reside there for generations. Human beings depend on the presence of oxygen for proper functioning and to maintain their physiological homeostasis. Under hypoxic conditions, adaptive long-term or compensatory short-term mechanism generate genetic, anatomical, physiological and in some cases pathological alterations among humans. OBJECTIVES: In this sense, we have set ourselves the objective of studying the epidemiological impact of living above 2,500 m above sea level as well as studying the most evident physiological differences between two genotype-controlled indigenous populations residing at low and high altitude. RESULTS: a) Anthropometric differences Our study shows that low altitude women tend to be shorter and heavier, but these differences are not statistically significant (p = 0.333), on the other hand, high altitude men are shorter than their counterparts who live at low altitude (p = 0.019). In relation to body composition, women at high altitudes have less body muscle % (-24.8%) while men at high altitudes have significantly more muscle body mass % (+ 13.5%) than their lowland counterpart. Body fat % is lower among low altitude women (-15.5%) and no differences were found among men. Hematological, lipid profile and cardiovascular risk differences 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 were higher among high altitude dwellers and the erythrocyte size was found to be smaller and SpO2% lower 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). b) Optimism and health self-perception High-altitude dwellers presented lower scores in all the studied dimensions of SF-36. Significant differences were found for the Role limitation sphere due to Vitality (p = 0.005), Mental Health (p = 0.002) and social functioning (p = 0.005). In all the cases, participants living at low altitudes scored higher than those living at high altitude. Lowland women were more optimistic than their high-altitude counterparts c) Lung function and spirometry parameters People from Oyacachi (3.800 m) showed a higher predicted value than those from Limoncocha (230 m). The FVC and the FEV1 were significantly greater among highlanders than lowlanders (p value < 0.001). The FEV1/FVC was significantly higher among lowlanders than highlanders for men and women. A restrictive pattern was found in 12.9% of the participants. 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. The anthropometric differences vary according to sex, demonstrating that high altitude population are in general lighter and shorter than their low altitude controls. Men at high altitude have more muscled bodies than their lowland counterpart but their biological age was older than their corresponding chronological age. High altitude dwellers had greater lung capacity than their low-altitude peers, a finding physiologically plausible according to published literature. When analyzing the spirometry patterns obtained in these populations, it was evident that greater lung capacities are probably linked to bigger lungs, improving systemic oxygenation despite low oxygen availability

Hematological parameters, lipid profile and cardiovascular risk analysis among genotype-controlled indigenous Kichwa 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, while at high altitude, 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 (RBC), Hemoglobin concentration and SpO2% were higher among high altitude dwellers and erythrocyte's size was found to be smaller at high altitude .The group located at low altitude showed also lower levels of plasma cholesterol, LDL and HDL but most of these differences are not influenced by gender or elevation. Conclusions: Living at altitude elicits well-known adaptive physiological changes such as erythrocyte count, hemoglobin concentration, hematocrit, and serum glucose. We report also clinical differences in the plasma lipid profile, with higher levels of cholesterol and high density and low-density lipoproteins in Andes Mountain inhabitants versus their Amazonian basin peers. Despite we found altered underlying physiological pathways between the populations, this does not allow in a different cardiovascular risk

Chronic high altitude exposure and the epidemiology of ischemic stroke: A systematic review

Introduction About 5.7% of the world population resides above 1,500 m. It has been hypothesized that acute exposure to high-altitude locations can increase stroke risk, while chronic hypoxia can reduce stroke-related mortality. Objective This review aims to provide an overview of the available evidence on the association between long-term high altitude exposure and ischemic stroke. Design A systematic review was performed from January 1st, 1960, to December 1st, 2021, to assess the possible link between high altitude exposure and ischemic stroke. The AMED, EMBASE, Cochrane Library, PubMed, MEDLINE, the European PubMed Central and the Latin-American bibliographic database Scielo were accessed using the University of Southampton library tool Delphis. In this review we included population and individual based observational studies, including cross sectional and longitudinal studies except for those merely descriptive individual-based case reports. Studies were limited to humans living or visiting high altitude locations for at least 28 days as a cut-off point for chronic exposure. Results We reviewed a total of 1,890 abstracts retrieved during the first step of the literature review process. The authors acquired in full text as potentially relevant 204 studies. Only 17 documents met the inclusion criteria and were finally included. Ten studies clearly suggest that living at high altitudes may be associated with an increased risk of stroke, however, five studies suggest that altitude may act as a protective factor for the development of stroke, while two studies report ambiguous results. Conclusions This review suggest that the most robust studies are more likely to find that prolonged living at higher altitudes reduces the risk of developing stroke or dying from it. Increased irrigation due to angiogenesis and increased vascular perfusion might be the reason behind improved survival profiles among those living within this altitude range. In contrast, residing above 3,500 m, seems to be associated with an apparent increased risk of developing stroke, probably linked to the presence of polycythaemia and other associated factors such as increased blood viscosity

Análisis de datos de exceso de mortalidad por infecciones y muertes por COVID-19 en Ecuador

The global COVID-19 pandemic has shocked the world. Since the virus gave rise to health problems and often ended in deaths, the count of the contagion and the deceased has been an open issue. Such statistics are vital for every nation and even every city or district and suburb as these numbers decide the level of intervention and the subsequent reduction of its given spread. Worldwide data show a mortality rate of around two percent prior to successful vaccination campaigns. However, Ecuador's statistical data indicate an abnormal amount of excess mortality, which is officially denied in each of the studied countries. These numbers have been projected on a monthly basis and exceed up to 300% of the official COVID-19 deaths. In particular, the average mortality rate in Ecuador, prior to and close to the pandemic, has been about 6083.4±234.6, while in the worst month during the sanitary crisis, deaths piled up to 21,000 people, and only 1180 were recognized as deceased by COVID-19. The reasons are widespread but based on an insufficient financed health sector, political incompetence, lack of leadership, and a long-lasting economic crisis. Therefore, premature endings of confinements or lockdowns have contributed to an accelerated contagion and seem to even counteract the vaccination phase, in middle 2021, shortly before excess mortality ceased completely.La pandemia mundial de COVID-19 ha conmocionado al mundo. Dado que el virus dio lugar a problemas de salud y, a menudo, terminó en muertes, el recuento del contagio y de fallecimientos ha sido un tema abierto. Estas estadísticas son vitales para cada nación e incluso para cada ciudad o distrito y suburbio, ya que estos números deciden el nivel de intervención y la consiguiente reducción de su extensión dada. Los datos mundiales indican una tasa de mortalidad de alrededor del dos por ciento antes de campañas de vacunación exitosas. Sin embargo, los datos estadísticos de Ecuador indican una cantidad anormal de exceso de mortalidad, que oficialmente se niega en cada uno de los países estudiados. Estas cifras se han proyectado mensualmente y superan hasta el 300 % de las muertes oficiales por COVID-19. En particular, en Ecuador la tasa de mortalidad promedio antes y cerca de la pandemia ha sido de alrededor de 6 083,4 ± 234,6, mientras que en el peor mes de la crisis sanitaria, las muertes ascendieron a 21 mil personas, pero solo se reconocieron 1 180 como personas fallecidas por COVID-19 o con este. Las razones son generalizadas, pero se basan en un sector de salud insuficientemente financiado, incompetencia política, falta de liderazgo y una crisis económica de larga duración. Por lo tanto, las terminaciones prematuras de los confinamientos o encierros han contribuido a un contagio acelerado y parecen incluso contrarrestar la fase de vacunación, a mediados de 2021, poco antes de que el exceso de mortalidad cesara por completo

Hispanic Ethnicity and the Risk of Cardiovascular Disease in the United States: The Behavioral Risk Factor Surveillance System 2013

BACKGROUND: Although the leading cause of death among Hispanics living in the United States (US) is cardiovascular disease (CVD), the association between Hispanic ethnicity and CVD has been scarcely explored. OBJECTIVE: To examine whether being Hispanic is associated with an increased risk of CVD compared with the non-Hispanic US adult population in 2013. METHODS: Secondary data analysis of a cross-sectional 2013 Behavioral Risk Factor Surveillance System survey in 2013 (n=486,905). The main exposure variable was Hispanic ethnicity (Mexican, Puerto Rican, Cuban or Spanish origin) and the main outcome variable was self-reported CVD (myocardial infarction/coronary artery disease/angina). The main covariates were sex, age, education, income, healthcare access, exercise, body mass index, current smoking, heavy drinking, diabetes, hypertension and hyperlipidemia. Unadjusted and adjusted logistic regressions were used to assess the effect between ethnicity and self-reported CVD. Odds ratios (OR) and 99% confidence intervals (CI) were calculated. RESULTS: In total, 12% of the study participants were Hispanic (n=57,257). Approximately 24% of Hispanics were 25-34 y/o while (21%) of non-Hispanic were \u3e65 y/o. After adjustment, Hispanics were 30% less likely to report CVD compared with non-Hispanics (OR=0.7; 99%; CI=0.6-0.8). Compared with men, women had a 40% decreased risk of having CVD (OR=0.60; 99% CI=0.5-0.6). Advanced age, lower educational attainment, income \u3c$15,000/year, lack of exercise, smoking, non-heavy drinking, diabetes, hypertension and hyperlipidemia increased statistically significantly the likelihood of reporting CVD. CONCLUSION: The findings suggest that, in general, Hispanics residing in the US are significantly less likely to self-declare if they had a CVD compared with non-Hispanic Americans. These data suggest that although Hispanics are generally poorer and have less access to education and health services, their self-perceived health is better than in non-Hispanic residents of the US

Stroke related mortality at different altitudes: A 17-year nationwide population-based analysis from Ecuador

Worldwide, more than 5.7% of the population reside above 1,500m 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. An ecological analysis of all stroke hospital admissions, mortality rates and disability-adjusted life years in Ecuador was performed from 2001-2017. The cases and population at risk were categorized in low (<1,500m), moderate (1,500m -2,500m), high (2,500m -3,500m) and very high altitude (3,500-5,500m) according to the place of residence. The derived crude and direct standardized age-sex adjusted mortality and hospital admission rates were calculated. 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 [CI95% 0.54 - 0.56]) and women (OR: 0.65 [CI95% [0.64 - 0.66]). 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 2,000m to 3,500 m

Genotyped indigenous Kiwcha adults at high altitude are lighter and shorter than their low altitude counterparts

Background Anthropometric measures have been classically used to understand the impact of environmental factors on the living conditions of individuals and populations. Most reference studies on development and growth in which anthropometric measures were used were carried out in populations that are located at sea level, but there are few studies carried out in high altitude populations. Objective The objective of this study was to evaluate the anthropometric and body composition in autochthonous Kiwcha permanently living at low and high altitudes. Methodology A cross-sectional study of anthropometric and body composition between genetically matched lowland Kiwcha from Limoncocha (n = 117), 230 m in the Amazonian basin, and high-altitude Kiwcha from Oyacachi (n = 95), 3800 m in Andean highlands. Student's t-test was used to analyze the differences between continuous variables, and the chi-square test was performed to check the association or independence of categorical variables. Fisher's exact test or Spearman's test was used when the variable had evident asymmetries with histograms prior to the selection of the test. Results This study shows that high altitude men are shorter than their counterparts who live at low altitude, with p = 0.019. About body muscle percentage, women at high altitudes have less body muscle percentage (− 24.8%). In comparison, men at high altitudes have significantly more muscle body mass percentage (+ 13.5%) than their lowland counterparts. Body fat percentage was lower among low altitude women (− 15.5%), and no differences were found among men. Conclusions This is the first study to be performed in two genotyped controlled matching populations located at different altitudes to our best knowledge. The anthropometric differences vary according to sex, demonstrating that high altitude populations are, in general, lighter and shorter than their low altitude controls. Men at high altitude have more muscled bodies compared to their lowland counterparts, but their body age was older than their actual age

Exceptional Prices of Medical and Other Supplies during the COVID-19 Pandemic in Ecuador.

Shortages of essential supplies used to prevent, diagnose, and treat COVID-19 have been a global concern, and price speculation and hikes may have negatively influenced access. This study identifies variability in prices of products acquired through government-driven contracts in Ecuador during the early pandemic response, when the highest mortality rates were registered in a single day. Data were obtained from the National Public Procurement Service (SERCOP) database between March 1 and July 31, 2020. A statistical descriptive analysis was conducted to extract relevant measures for commonly purchased products, medical devices, pharmaceutical drugs, and other goods. Among the most frequently purchased products, the greatest amounts were spent on face masks (US$4.5 million), acetaminophen (US$2.2 million), and reverse transcriptase quantitative polymerase chain reaction assay kits (US$1.8 million). Prices varied greatly, depending on each individual contract and on the number of units purchased; some were exceptionally higher than their market value. Compared with 2019, the mean price of medical examination gloves increased up to 1,307%, acetaminophen 500 mg pills, up to 796%, and oxygen flasks, 30.8%. In a context of budgetary constraints that actually required an effective use of available funds, speculative price hikes may have limited patient access to health care and the protection of the general population and health care workers. COVID-19 vaccine allocations to privileged individuals have also been widely reported. Price caps and other forms of regulation, as well as greater scrutiny and transparency of government-driven purchases, and investment in local production, are warranted in Ecuador for improved infectious disease prevention

A comparative analysis of lung function and spirometry parameters in genotype-controlled natives living at low and high altitude

Background: The reference values for lung function are associated to anatomical and lung morphology parameters, but anthropometry it is not the only influencing factor: altitude and genetics are two important agents affecting respiratory physiology. Altitude and its influence on respiratory function has been studied independently of genetics, considering early and long-term acclimatization. Objective: The objective of this study is to evaluate lung function through a spirometry study in autochthonous Kichwas permanently living at low and high-altitude. Methodology: A cross-sectional study of spirometry differences between genetically matched lowland Kichwas from Limoncocha (230 m) at Amazonian basin and high-altitude Kichwas from Oyacachi (3,180 m) in Andean highlands. Chi-square method was used to analyze association or independence of categorical variables, while Student's t test was applied to comparison of means within quantitative variables. ANOVA, or in the case that the variables didn't meet the criteria of normality, Kruskal Wallis test were used to compare more than two groups. Results: People from Oyacachi (high altitude) showed a higher predicted values than those from Limonocha (low altitude). The FVC and the FEV1 were significantly greater among highlanders than lowlanders (p value < 0.001). The FEV1/FVC was significantly higher among lowlanders than highlanders for men and women. A restrictive pattern was found in 12.9% of the participants. Conclusion: Residents of Oyacachi had greater lung capacity than their peers from Limoncocha, a finding physiologically plausible according to published literature. When analyzing the spirometric patterns obtained in these populations, it was evident that no person had an obstructive pattern, while on the other hand, the restrictive pattern appeared in Limoncocha and Oyacachi populations in 12.9% although it is clear that there is a predominance of this in the individuals belonging to Limoncocha

Long COVID at different altitudes: A Countrywide Epidemiological Analysis

Background: Several reports from around the world have reported that some patients who have recovered from COVID-19 have experienced a range of persistent or new clinical symptoms after a SARS-CoV-2 infection. These symptoms can last from weeks to months, impacting everyday functioning to a significant number of patients. Methods: A cross-sectional analysis based on an online, self-reporting questionnaire was conducted in Ecuador from April to July 2022. Participants were invited by social media, radio, and TV to voluntarily participate in our study. A total of 2103 surveys were included in this study. We compared socio-demographic variables and long-term persisting symptoms at low (2500 m). Results: Overall, 1100 (52.3%) responders claimed to have Long-COVID symptoms after SARS-CoV-2 infection. Most of these were reported by women (64.0%); the most affected group was young adults between 21 to 40 years (68.5%), and most long-haulers were mestizos (91.6%). We found that high altitude residents were more likely to report persisting symptoms (71.7%) versus those living at lower altitudes (29.3%). The most common symptoms were fatigue or tiredness (8.4%), hair loss (5.1%) and difficulty concentrating (5.0%). The highest proportion of symptoms was observed in the group that received less than 2 doses. Conclusions: This is the first study describing post-COVID symptoms' persistence in low and high-altitude residents. Our findings demonstrate that women, especially those aging between 21-40, are more likely to describe Long-COVID. We also found that living at a high altitude was associated with higher reports of mood changes, tachycardia, decreased libido, insomnia, and palpitations compared to lowlanders. Finally, we found a greater risk to report Long-COVID symptoms among women, those with previous comorbidities and those who had a severer acute SARS-CoV-2 infection