Sea Level Subjects Research Articles

Higher prevalence of unrecognized kidney disease at high altitude.

High altitude renal syndrome has been described in populations with excessive erythrocytosis. We evaluated whether high altitude (HA) dwellers might be at increased risk for kidney disease. We performed a cross-sectional study to investigate differences in prevalence of kidney function and metabolic syndrome in healthy subjects living at HA vs. sea level (SL) without any known history of hypertension, diabetes or chronic kidney disease. We examined 293 subjects, aged 40 to 60 years: 125 SL (154m) and 168 HA (3640m) dwellers. HA dwellers had higher serum creatinine, lower estimated glomerular function rate (eGFR) (69.5 ± 15.2 vs. 102.1 ± 17.8ml/min/1.73m2, p < 0.0001), more proteinuria and higher hemoglobin concentrations compared to SL subjects. HA subjects had a lower prevalence of metabolic syndrome. Hemoglobin concentrations correlated inversely with eGFR in female (p = 0.001) and male (p = 0.03) HA dwellers. Using logistic regression analysis to compare subjects with eGFR < 90 vs. > 90ml/min/1.73m2, a lower eGFR was associated with female gender (odds ratio adjusted: 5.65 [95% confidence interval: 2.43-13.13]; p = 0.001), high altitude (14.78 [6.46-33.79]; p = 0.001), hemoglobin (1.68 [1.16-2.43]; p = 0.001) and uric acid (1.93 [1.36-2.72]; p = 0.001). Dwellers at high altitude who are considered healthy have worse kidney function, a higher prevalence of proteinuria and a lower prevalence of metabolic syndrome compared to people living at SL.

Hematological and Physiological Adaptations Following 46 Weeks of Moderate Altitude Residence

Although acclimatization to moderate altitude (MA) is thought to be unnecessary or to require minimal adaptation, retrospective data from the U.S. Air Force Academy (USAFA), a military college located at 2210 m, suggested otherwise. To further examine the utility of USAFA as a model for MA acclimatization, a longitudinal experimental design was prospectively utilized to determine the magnitude and time course of selected hematological and performance parameters following 46 weeks at this unique MA setting. Incoming USAFA male freshmen (n=55) were divided into experimental groups based on prior residence at sea level (SL) or MA. Hematological and performance parameters were repeatedly assessed during their entire first year at MA. Hematological data consisted of a complete blood count (CBC) with reticulocyte parameters, as well as determination of serum levels of ferritin, erythropoietin, and soluble transferrin receptor (sTfR). Performance testing included aerobic (1.5-mile run) and physical (push-ups, sit-ups, pull-ups, and standing long jump) fitness tests, maximal aerobic capacity, and running economy. Significant (p<0.05; main effect) hematological differences between SL and MA subjects were observed for the majority of the study. MA subjects had a significantly higher hemoglobin concentration ([Hb], +5.5%), hematocrit (+2.8%), and serum ferritin (+59.0%) and significantly lower sTfR (-11.4%) values than their SL peers. Although both serum ferritin and sTfR demonstrated a significant altitude group x time interaction, [Hb] and hematocrit did not. A significant main effect of altitude without interaction was also observed for performance parameters, with SL subjects having a significantly lower Vo2peak (-5.9%), slower 1.5- mile run time (+5.4%), poorer running economy (+6.6%), and lower composite physical fitness test score (-13.9%) than MA subjects. These results suggest that complete acclimatization to 2210 m by former SL residents may require lengthy physiological adaptations, as both hematological and physical performance differences persisted between groups. Further research at this uniquely well controlled MA setting is warranted.

Pulmonary Pressure and Cardiac Function in Chronic Mountain Sickness Patients

Chronic mountain sickness (CMS) is characterized by a loss of adaptation to hypoxia in high-altitude (HA) dwellers. Chronic hypoxemia, excessive erythrocytosis and frequently pulmonary hypertension (PH), which may lead to cardiac failure, develop in patients. We sought to assess the determinants of cardiac function in CMS patients with hypoxia-induced PH. Fifteen healthy men living at sea level (SL) were compared to 15 healthy men living at HA and 55 patients with CMS from Cerro de Pasco, Peru (altitude, 4,300 m). Pulmonary pressures and cardiac function were estimated by echocardiography. None of the subjects had overt cardiac failure symptoms. CMS patients exhibited elevated mean pulmonary pressures as assessed by high-tricuspid pressure gradients (CMS patients, 34 +/- 10 mm Hg; HA subjects, 25 +/- 4 mm Hg [p = 0.002]; and SL subjects, 19 +/- 3 mm Hg [p < 0.001]). They also showed right ventricular (RV) dilation (mean end-diastolic RV area: CMS patients, 17 +/- 2 cm(2); HA subjects, 13 +/- 2 cm(2); SL subjects, 12 +/- 2 cm(2); p < 0.001) but did not display impaired systolic ventricular function. However, the RV Tei index was increased in CMS and HA subjects (CMS patients, 0.56 +/- 0.15; HA subjects, 0.52 +/- 0.12; SL subjects, 0.21 +/- 0.12; p < 0.001). Despite obvious pulmonary arterial hypertension and right heart dilation, CMS patients did not show any symptom or echocardiographic parameter of heart failure. ClinicalTrials.gov. Identifier: NCT00424970.

Physical Fitness and Hematological Changes During Acclimatization to Moderate Altitude: A Retrospective Study

While high altitude adaptations have been studied extensively, limited research has examined moderate altitude (MA: 1500 to 3000 m) adaptations and their time course, despite the fact that millions of people sojourn to or reside at MA. We retrospectively examined long-term MA acclimatization by analyzing recurring physical fitness test results and hematological data among 2147 college-age male cadets previously residing at either sea level (SL) or MA and currently attending the U.S. Air Force Academy (USAFA), a unique, regimented, and well-controlled military university located at 2210 m. Significant (p < 0.01) differences were found in aerobic and anaerobic fitness test scores between former SL and MA subjects, with MA subjects scoring 27 points (8%) higher during a 1.5-mile aerobic fitness run and 18 points (6%) higher than SL subjects in the anaerobic fitness test for 2 yr. These differences may be partly explained by the hematological differences observed. Hemoglobin concentration ([Hb]) was significantly (p < 0.001) higher (6.3%; approximately 1 g/dL) in MA subjects prior to arrival at USAFA and acutely, but the difference between altitude conditions was gone at the next retrospective blood draw (+17 months). After 2.5 yr at USAFA, former SL residents had significantly (p < 0.001) higher [Hb] by +10%, or 1.5 g/dL versus prearrival values. This study suggests that significant hematological acclimatization occurs with MA exposure and requires greater than 7 months to reach stability. The altitude-induced erythropoiesis may explain in part the improvements in aerobic performance, but altitude-related anaerobic differences still remain after hematological acclimatization.

ANTIOXIDANT SUPPLEMENTATION DOES NOT REDUCE INCIDENCE OR SEVERITY OF ACUTE MOUNTAIN SICKNESS AT 4300 M

The pathophysiology of acute mountain sickness (AMS) may be related to oxidative stress raising the possibility that antioxidants represent an alternate therapy for AMS. PURPOSE To test the hypothesis that antioxidant supplementation would decrease the incidence and severity of AMS during two weeks of elevated energy expenditure and caloric deficit at 4300 m. METHODS Eighteen trained males (25 ± 1 yr, mean ± SE) completed the Environmental Symptoms Questionnaire III (ESQ) and Lake Louise Questionnaire (LLQ) at sea level (SL) and daily during two weeks at high altitude (HA) (4300 m). During both SL and HA testing subjects were provided with a low antioxidant diet that maintained caloric balance at SL. However, while at HA energy expenditure was increased to achieve a caloric deficit of ∼1500 kcal·d−1. Following SL testing subjects were divided into two groups matched for ventilatory chemosensitivity, VO2peak, body mass, body composition, and age. In double blind fashion the two groups were assigned to either the placebo (PL) or antioxidant (AO) group and began supplementation three weeks prior to going to HA. RESULTS There were no significant differences in AMS incidence or severity between PL and AO on any day. The incidence of AMS as measured by the ESQ AMS- Cerebral factor score (AMS-C) peaked on day 1 of HA with 13 of 18 subjects reaching the criterion score. The AMS-C score was significantly elevated above SL on days 1–4 of HA (SL 0.156 ± 0.051 vs. HA1–4 0.964 ± 0.321, P < 0.05). These results were confirmed with the analysis of the ESQ AMS-Respiratory factor score and LLQ data. CONCLUSIONS Antioxidant supplementation does not reduce the incidence or severity of AMS during two weeks of elevated energy expenditure and caloric deficit at 4300 m. Supported by the Departments of Veterans Affairs and Defense