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High Alt Med Biol ; 18(1): 11-19, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28306414


Pham, Luu V., Christopher Meinzen, Rafael S. Arias, Noah G. Schwartz, Adi Rattner, Catherine H. Miele, Philip L. Smith, Hartmut Schneider, J. Jaime Miranda, Robert H. Gilman, Vsevolod Y. Polotsky, William Checkley, and Alan R. Schwartz. Cross-sectional comparison of sleep-disordered breathing in native Peruvian highlanders and lowlanders. High Alt Med Biol. 18:11-19, 2017. BACKGROUND: Altitude can accentuate sleep disordered breathing (SDB), which has been linked to cardiovascular and metabolic diseases. SDB in highlanders has not been characterized in large controlled studies. The purpose of this study was to compare SDB prevalence and severity in highlanders and lowlanders. METHODS: 170 age-, body-mass-index- (BMI), and sex-matched pairs (age 58.2 ± 12.4 years, BMI 27.2 ± 3.5 kg/m2, and 86 men and 84 women) of the CRONICAS Cohort Study were recruited at a sea-level (Lima) and a high-altitude (Puno, 3825 m) setting in Peru. Participants underwent simultaneous nocturnal polygraphy and actigraphy to characterize breathing patterns, movement arousals, and sleep/wake state. We compared SDB prevalence, type, and severity between highlanders and lowlanders as measured by apnea-hypopnea index (AHI) and pulse oximetry (SPO2) during sleep. RESULTS: Sleep apnea prevalence was greater in highlanders than in lowlanders (77% vs. 54%, p < 0.001). Compared with lowlanders, highlanders had twofold elevations in AHI due to increases in central rather than obstructive apneas. In highlanders compared with lowlanders, SPO2 was lower during wakefulness and decreased further during sleep (p < 0.001). Hypoxemia during wakefulness predicted sleep apnea in highlanders, and it appears to mediate the effects of altitude on sleep apnea prevalence. Surprisingly, hypoxemia was also quite prevalent in lowlanders, and it was also associated with increased odds of sleep apnea. CONCLUSIONS: High altitude and hypoxemia at both high and low altitude were associated with increased SDB prevalence and severity. Our findings suggest that a large proportion of highlanders remain at risk for SDB sequelae.

Altitud , Respiración , Índice de Severidad de la Enfermedad , Síndromes de la Apnea del Sueño/fisiopatología , Anciano , Índice de Masa Corporal , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oximetría , Perú/epidemiología , Perú/etnología , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Síndromes de la Apnea del Sueño/epidemiología , Síndromes de la Apnea del Sueño/etiología
High Alt Med Biol ; 17(3): 208-213, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27454014


Healy, Katherine, Alain B. Labrique, J. Jaime Miranda, Robert H. Gilman, David Danz, Victor G. Davila-Roman, Luis Huicho, Fabiola León-Velarde, and William Checkley. Dark adaptation at high altitude: an unexpected pupillary response to chronic hypoxia in Andean highlanders. High Alt Med Biol. 17:208-213, 2016.-Chronic mountain sickness is a maladaptive response to high altitude (>2500 m above sea level) and is characterized by excessive erythrocytosis and hypoxemia resulting from long-term hypobaric hypoxia. There is no known early predictor of chronic mountain sickness and the diagnosis is based on the presence of excessive erythrocytosis and clinical features. Impaired dark adaptation, or an inability to visually adjust from high- to low-light settings, occurs in response to mild hypoxia and may serve as an early predictor of hypoxemia and chronic mountain sickness. We aimed to evaluate the association between pupillary response assessed by dark adaptometry and daytime hypoxemia in resident Andean highlanders aged ≥35 years living in Puno, Peru. Oxyhemoglobin saturation (SpO2) was recorded using a handheld pulse oximeter. Dark adaptation was quantitatively assessed as the magnitude of pupillary contraction to light stimuli of varying intensities (-2.9 to 0.1 log-cd/m2) using a portable dark adaptometer. Individual- and stimulus-specific multilevel analyses were conducted using mixed-effect models to elicit the relationship between SpO2 and pupillary responsiveness. Among 93 participants, mean age was 54.9 ± 11.0 years, 48% were male, 44% were night blind, and mean SpO2 was 89.3% ± 3.4%. The magnitude of pupillary contraction was greater with lower SpO2 (p < 0.01), and this dose relationship remained significant in multiple variable analyses (p = 0.047). Pupillary responsiveness to light stimuli under dark-adapted conditions was exaggerated with hypoxemia and may serve as an early predictor of chronic mountain sickness. This unexpected association is potentially explained as an excessive and unregulated sympathetic response to hypoxemia at altitude.

High Alt Med Biol ; 17(2): 93-100, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27281472


Miele, Catherine H., Alan R. Schwartz, Robert H. Gilman, Luu Pham, Robert A. Wise, Victor G. Davila-Roman, Jonathan C. Jun, Vsevolod Y. Polotsky, J. Jaime Miranda, Fabiola Leon-Velarde, and William Checkley. Increased cardiometabolic risk and worsening hypoxemia at high altitude. High Alt Med Biol. 17:93-100, 2016.-Metabolic syndrome, insulin resistance, diabetes, and dyslipidemia are associated with an increased risk of cardiovascular disease. While excessive erythrocytosis is associated with cardiovascular complications, it is unclear how worsening hypoxemia of any degree affects cardiometabolic risk factors in high-altitude populations. We studied the relationship between daytime resting oxyhemoglobin saturation and cardiometabolic risk factors in adult participants living in Puno, Peru (3825 m above sea level). We used multivariable logistic regression models to study the relationship between having a lower oxyhemoglobin saturation and markers of cardiometabolic risk. Nine hundred and fifty-four participants (mean age 55 years, 52% male) had information available on pulse oximetry and markers of cardiometabolic risk. Average oxyhemoglobin saturation was 90% (interquartile range 88%-92%) and 43 (4.5%) had excessive erythrocytosis. Older age, decreased height-adjusted lung function, and higher body mass index (BMI) were associated with having an oxyhemoglobin saturation ≤85%. When adjusting for age, sex, socioeconomic status, having excessive erythrocytosis, and site, we found that each 5% decrease in oxyhemoglobin saturation was associated with a higher adjusted odds of metabolic syndrome (OR = 1.35, 95% CI: 1.07-1.72, p < 0.04), insulin resistance as defined by homeostasis model assessment-insulin resistance (HOMA-IR) >2 mass units (OR = 1.29, 95% CI: 1.00-1.67, p < 0.05), hemoglobin A1c ≥6.5% (OR = 1.66, 95% CI: 1.09-2.51, p < 0.04), and high sensitivity C-reactive protein (hs-CRP) ≥3 mg/L (OR = 1.46, 95% CI: 1.09-1.96, p < 0.01). In high-altitude populations in Puno, Peru, a higher BMI and lower pulmonary function were associated with lower resting daytime oxyhemoglobin saturation. Lower resting oxyhemoglobin saturation, in turn, was associated with higher odds of having multiple unfavorable cardiometabolic factors. Worsening hypoxia of any degree in high-altitude dwellers may be an independent risk factor for cardiovascular disease.

Altitud , Enfermedades Cardiovasculares/etiología , Progresión de la Enfermedad , Hipoxia/complicaciones , Síndrome Metabólico/etiología , Adulto , Biomarcadores/sangre , Índice de Masa Corporal , Proteína C-Reactiva/análisis , Femenino , Humanos , Hipoxia/sangre , Hipoxia/fisiopatología , Resistencia a la Insulina , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oximetría , Oxihemoglobinas/análisis , Perú , Policitemia/sangre , Policitemia/complicaciones , Descanso/fisiología , Factores de Riesgo
High Alt Med Biol ; 16(2): 162-8, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25973777


Vyas, Kaetan J., David Danz, Robert H. Gilman, Robert A. Wise, Fabiola León-Velarde, J. Jaime Miranda, and William Checkley. Noninvasive assessment of excessive erythrocytosis as a screening method for chronic mountain sickness at high altitude. High Alt Med Biol 16:162-168, 2015.--Globally, over 140 million people are at risk of developing chronic mountain sickness, a common maladaptation to life at high altitude (>2500 meters above sea level). The diagnosis is contingent upon the identification of excessive erythrocytosis (EE). Current best practices to identify EE require a venous blood draw, which is cumbersome for large-scale surveillance. We evaluated two point-of-care biomarkers to screen for EE: noninvasive spot-check tests of total hemoglobin and oxyhemoglobin saturation (Pronto-7, Masimo Corporation). We conducted paired evaluations of total serum hemoglobin from a venous blood draw and noninvasive, spot-check testing of total hemoglobin and oxyhemoglobin saturation with the Pronto-7 in 382 adults aged ≥35 years living in Puno, Peru (3825 meters above sea level). We used the Bland-Altman method to measure agreement between the noninvasive hemoglobin assessment and the gold standard lab hemoglobin analyzer. Mean age was 58.8 years and 47% were male. The Pronto-7 test was unsuccessful in 21 (5%) participants. Limits of agreement between total hemoglobin measured via venous blood draw and the noninvasive, spot-check test ranged from -2.8 g/dL (95% CI -3.0 to -2.5) to 2.5 g/dL (95% CI 2.2 to 2.7), with a bias of -0.2 g/dL (95% CI -0.3 to -0.02) for the difference between total hemoglobin and noninvasive hemoglobin concentrations. Overall, the noninvasive spot-check test of total hemoglobin had a better area under the receiver operating characteristic curve compared to oxyhemoglobin saturation for the identification of EE as measured by a gold standard laboratory hemoglobin analyzer (0.96 vs. 0.82; p<0.001). Best cut-off values to screen for EE with the Pronto 7 were ≥19.9 g/dL in males and ≥17.5 g/dL in females. At these cut-points, sensitivity and specificity were both 92% and 89% for males and females, respectively. A noninvasive, spot-check test of total hemoglobin had low bias and high discrimination for the detection of EE in high altitude Peru, and may be a useful point-of-care tool for large-scale surveillance in high-altitude settings.

Mal de Altura/diagnóstico , Altitud , Pruebas Hematológicas/instrumentación , Sistemas de Atención de Punto/estadística & datos numéricos , Policitemia/sangre , Adulto , Anciano , Mal de Altura/sangre , Enfermedad Crónica , Femenino , Pruebas Hematológicas/estadística & datos numéricos , Hemoglobinas/análisis , Humanos , Masculino , Persona de Mediana Edad , Perú , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
High Alt Med Biol ; 16(1): 26-33, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25760230


Painschab, Matthew S., Gary E. Malpartida, Victor G. Davila-Roman, Robert H. Gilman, Todd M. Kolb, Fabiola Leon-Velarde, J. Jaime Miranda, and William Checkley. Association between serum concentrations of hypoxia inducible factor responsive proteins and excessive erythrocytosis in high altitude Peru. High Alt Med Biol 16:26-33, 2015.-Long-term residence at high altitude is associated with the development of chronic mountain sickness (CMS), which is characterized by excessive erythrocytosis (EE). EE occurs under chronic hypoxia, and a strongly selected mutation in hypoxia-inducible factor 2α (HIF2A) has been found in native Tibetans that correlates with having a normal hemoglobin at high altitude. We sought to evaluate differences in plasma levels of four HIF-responsive proteins in 20 participants with EE (hemoglobin >21 g/dL in men and >19 in women) and in 20 healthy, age- and sex-matched participants without EE living at high altitude in Puno, Peru. We performed ELISA to measure plasma levels of the four HIF-responsive proteins: vascular endothelial growth factor (VEGF), soluble VEGF receptor 1 (sVEGF-R1), endothelin-1, and erythropoietin. As a secondary aim, we evaluated the association between HIF-responsive proteins and echocardiography-estimated pulmonary artery systolic pressure (PASP) in a subset of 26 participants. sVEGF-R1 was higher in participants with vs. without EE (mean 107 pg/mL vs. 90 pg/mL; p=0.007). Although plasma concentrations of endothelin-1, VEGF, and erythropoietin were higher in participants with vs. without EE, they did not achieve statistical significance (all p>0.25). Both sVEGF-R1 (p=0.04) and erythropoietin (p=0.04) were positively associated with PASP after adjustment for age, sex, and BMI. HIF-responsive proteins may play a pathophysiological role in altitude-related, chronic diseases but our results did not show consistent changes in all measured HIF-responsive proteins. Larger studies are needed to evaluate for additional genetic and environmental risk factors.

Mal de Altura/sangre , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/sangre , Hipoxia/sangre , Policitemia/sangre , Adulto , Anciano , Altitud , Biomarcadores/sangre , Presión Sanguínea , Estudios de Casos y Controles , Endotelina-1/sangre , Eritropoyetina/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Perú , Arteria Pulmonar/fisiología , Receptor 1 de Factores de Crecimiento Endotelial Vascular/sangre , Factores de Crecimiento Endotelial Vascular/sangre