Our anthropometric evaluation considered body weight (BW, kg) and height (cm) using a scale balance (SECA model 767) to calculate body mass index (BMI, BMI = kg/m²). Waist circumference (WC, cm) was measured using inextensible metric tape (SECA model 201). Body fat mass was determined by measuring four skinfolds: bicipital, tricipital, subscapular, and suprailiac (Lange skinfold, Cambridge, Maryland) percentage of adipose (Fatty body, %) was calculated using the protocol described by Durnin and Womersley (1974); and, finally, we calculated fat mass (FM, kg) as FM = (BW*FB)/100 and lean body mass (LBM, kg) as LBM = BW − FM. All anthropometrical measurements were made by the same evaluator. Table 1 shows the classifications of cardiovascular risk concerning BMI, WC, body fat (%), and LBM (kg; Bray, 1998; Jensen et al., 2013; Macek et al., 2020). After evaluation of corporal composition, we measured oxygen saturation (SpO2, %) and heart rate (HR, bpm) by pulse oximetry (model 7500FO Nonin) and systolic arterial pressure (SAP) and diastolic arterial pressure (DAP) using a cardiorespiratory monitor (model BM3, Bionet).

We collected blood samples from the brachial vein before entering the shift (between 07:00 and 08:00 am) on day 3 at the indicated altitude. Blood samples were centrifuged immediately after collection (3,000 rpm for 20 min) and the plasma fraction was frozen at −80°C until analysis. To measure high sensitive CRP (hsCRP) levels, an ELISA test was performed in duplicate using a commercial kit for serum and plasma (Human CRP/CRP Quantikine ELISA Kit; catalog number: DCRP00; R&D Systems, Minneapolis, MN 55413). Table 1 shows the CV risk criteria according to the plasma level of hsCRP.

Values presented in tables were expressed as the mean ± SD. Non-parametrical variables obtained in our study, such as percentages (%) were analyzed by proportional tests. Comparison of parametrical variables was analyzed using one-way ANOVA, and differences between different altitudes were evaluated by a Newman-Keuls test. Differences were considered statistically significant when values of p < 0.05. Pearson’s correlation was also performed; the analysis was carried out to establish the association between hsCRP (dependent variable) with anthropometrical and cardiometabolic variables. All statistical analyses were performed with GraphPad Prism Software (version 5.03, GraphPad Software, Inc.).

Populations studied here showed no variation in BW, BMI, body fatty (BF), FM, LBM, and waist perimeter between the levels evaluated (Table 2). However, when analyzing populations based on the established criteria (Table 1), we observed BMI values in the overweight and obese range at sea level, 1,600, and 2,500 m of 80, 75, and 84%, respectively, and BF (%) values of 57.5, 57.5, and 58.5%, respectively. Additionally, we observed WC measurements which corresponded to a high risk of cardiovascular disease (over 94 cm) at sea level, 1,600, and 2,500 m of 43, 48.6, and 52.9%, respectively.

We performed cardiorespiratory evaluations at each altitude and observed a progressive decline in arterial oxygenation with increasing altitude (Table 4). Conversely, cardiovascular variables such as systolic and diastolic blood pressure and HR increased with altitude (Table 4). Additionally, we observed that hs-CRP levels in plasma significantly increased at 2,500 m, compared to sea level and 1,600 m (Figure 1), and we observed a significant increase in the percentage of subjects with values over 3 mg/L (which indicates an increased risk of cardiovascular disease, see Table 1); 33.3% at 2,500 m compared with 9.6 and 8.5% at sea level and 1,600 m, respectively. Supplementary Table shows the correlation between hsCRP vs. anthropometrical and cardiometabolic variables, where we observed a positive and significant correlation with SAP and a negative and significant correlation with VO₂ max (expressed mlO2/min/kg and mlO2/min/kg LBM) at 2,500 m. Additionally, a positive and significant correlation was observed with BF, LBM, and WC and a negative and significant correlation was observed with VO₂ max (mlO2/min/kg).

Resting and maximum values of cardiorespiratory and metabolic parameters at sea level, 1,600, and 2,500 m are shown in Table 5. We observed a significant difference between resting and maximum exercise in VO₂, SpO2, HR, VE, and RER (p < 0.05). Additionally, when we compared cardiorespiratory and metabolic responses obtained at rest at sea level and high altitude, we observed a significant decline in oxygen saturation at 1,600 and 2,500 m (p < 0.05) and a significant increase in HR at 2,500 m (p < 0.05). No difference was observed in VO₂, VE, and RER (p > 0.05). However, when we compared cardiorespiratory and metabolic responses obtained at maximum exercise, we observed a progressive decline in maximum oxygen consumption (expressed mlO2/min/kg) at 2,500 m (p < 0.05). We observed a similar pattern when comparing maximum oxygen consumption and LBM. These low VO₂ max levels were obtained at the same intensity (Watts), RER, VE, and HR at sea level, 1,600, and 2,500 m. However, a gradual decrease in oxygen saturation was observed during maximum exercise at 1,600 and 2,500 m (p < 0.05).

Our study shows that the average anthropometric values (BMI, BF, MF, WC) in the miners were higher than the national average according to the 2010 National Health Survey (Ministry of Health Chile, n.d.). Similar results were described in a Chilean miner population with CIHH exposure (Pedreros et al., 2018) who presented higher obesity and overweight rates. Additionally, increased blood pressure, cholesterol, and glucose levels were observed in workers of the mining industry exposed to intermittent high-altitude hypoxia at 3,700–4,000 m in the Kyrgyz Republic (Esenamanova et al., 2014). However, in a prospective study performed in Chilean miners without previous exposure to high altitude (3,800–4,600 m), it was shown that BW and body composition did not change significantly after 31-month (Richalet et al., 2002). The anthropometric information we collected in the present study is contradictory to that indicated in the literature. In the literature, it has been described that exposure to altitude under an acute exposure model leads to weight loss, due to a negative energy balance mainly caused by an increased basal metabolic rate and suppression of appetite (Lippl et al., 2010). Some studies have even shown that staying in a hypobaric hypoxic environment could even be used as a treatment for obesity due to the reasons noted above (Lippl et al., 2010; Palmer and Clegg, 2014; Karl et al., 2018). However, regarding our result, we do not observe that this positive effect translates into a reduction in overweight and obesity in our population. We believe that our results are due to lifestyles where energy intake exceeds expenditure (Vearrier and Greenberg, 2011), which could be partially explained by cultural aspects, such as the mining organizational structure, workers union pressure, and mining worker food-culture. A study published on miners with cardiovascular risk factors showed that the daily energy intake that a worker consumes could reach 6,378 Kcal/day, and was largely made up of energy-dense foods rich in simple sugars, sodium, cholesterol, saturated fatty acids, and with a low fiber content (Padilla, 1999). However, another study classified miner’s physical activities as low in administrative workers (estimation of 2.2–2.4 Kcal/day), moderate in truck operators (estimation of 2.4–2.6 Kcal/day), and active in mechanical workers (estimated 2.8–3.0 Kcal/day; Caichac et al., 2013). In our study, we considered the population represented by truck operators to have a physical activity rate as light or sedentary.

High altitude is associated with increased sympathetic tone and may result in elevated blood pressure (Richalet et al., 1992; Naeije, 2010). In a previous study, the authors measured arterial blood pressure for 24 h in miners at sea level and high altitude (3,800 m) and found that the mean arterial pressure at high altitude was higher than at sea level, supporting the notion that high altitude leads to increased sympathetic tone (Richalet et al., 2002). Additionally, the authors found a reduction in mean arterial pressure after 31 months of exposure to CIHH. A similar response was described in the miner’s population exposed to CIHH at 4,000 m (Kyrgyzstan; Vinnikov et al., 2016). In contrast, in another miner population exposed to CIHH at 3,700–4,000 m, high overweight and obesity rates are prevalent and associated with increased blood pressure (Esenamanova et al., 2014). However, in our study, we did not observe any changes and /or presence of subjects with elevated arterial pressure in the population exposed to sea level compared to 1,600 or 2,500 m.

We observed a significant increase in hsCRP plasma concentration at 1,600 and 2,500 m in miners exposed to CIHH. It was previously shown that non-specific inflammation could be induced by hypoxia and contribute to high altitude-associated diseases. Three studies have found increased levels of IL-6 and CRP at high altitude compared to baseline levels during both passive or active ascent of Capanna Regina Margherita (4,559 m). IL-6 peaked on the second day and declined to baseline during the following 3 days. Additionally, CRP levels increased on day 3 and remained elevated before descending (Hartmann et al., 2000; Bailey et al., 2004). A study performed on subjects without previous prolonged exposure to high altitude showed that these people presented increased plasma hsCRP levels when they stayed at 4,000 m for 3 months (Hu et al., 2016). In these studies, the authors proposed that hypoxia at high altitudes could be considered a new inflammatory stimulus below the range expected for inflammatory diseases, such as acute mountain sickness or HAPE. Early studies describe a high increase in IL-6 and CRP levels with HAPE in subjects at 4,559 m (Kleger et al., 1996). However, no miner exposed to CIHH at 4,500 m suffered from severe forms of mountain sickness (HAPE or HACE; Richalet et al., 2002) and an incidence of HAPE 0.49% and no coronary events were observed during the construction of the Qinghai-Tibet railroad (Wu et al., 2007). Also, in our study, we did not observe HAPE at 1,600 and 2,500 m. The higher hsCRP values in miners could also be explained by the high prevalence of overweight and obesity levels previously described: since obesity (excess adipose tissue) is characterized by a state of permanent mild inflammation with increased circulating levels of inflammatory markers such as hsCRP, IL-6, TNF∝, and others (more detail see Kayser and Verges, 2013). However, the high prevalence of overweight and obesity described in the present study is not related to altitude, suggesting that the observed increase is the result of altitude exposure. A study performed in Puno-Perú (3,825 m) show elevated values of hsCRP (>3 mg/L) in individuals with lower values of oxygen saturation (Miele et al., 2016). Also, lower resting daytime oxygen saturation may serve as a marker of increased cardiovascular risk at high altitudes (Grundy et al., 2004).

Many studies have reported the fall in VO₂ max at high altitudes (see West, 2006). A study performed by Cerretelli (1980) reports that this fall is consistent with acute or chronic exposure and Kayser (2005) reported a VO₂ maximum decrease by 1% for every additional 100 m elevation over 1,500 m. Therefore, VO₂ max could decrease by 1–2% at 1,600 m and a reduction of 10% in the VO₂ max at 2,500. However, our results showed a reduction of 11.6% of VO₂ max at 1,600 m and 25.9% at 2,500 m, a difference of nearly 10% at 1,600 m and 15.9% at 2,500 m. We previously described a 29% reduction in VO₂ max in miners exposed CIHH at 3,800 m. This reduction was similar to that described by other authors associated with a decreased intensity (Sutton et al., 1988). However, in our previous studies, this fall in VO₂ max does not correlate with a fall in intensity and was interpreted as an increase in work efficiency at 3,800 m (Moraga et al., 2018, 2019) due to a major effort in the respiratory muscle work (see discussion, Moraga et al., 2019). In contrast, we reported a reduction of 25.9% in the VO₂ max at 2,500 m where the intensity of exercise, VE, and HR was lower than that described at 3,800 m (Moraga et al., 2019). A possible explanation for the lower aerobic capacity in our study population could be a worse physical condition, since over 70% of subjects were sedentary, overweight, and aged. This worse physical condition could be corroborated by values of maximal effort (extenuating) at the lower value of 200 Watts at 1,600 and 2,500 m and lower HR values. Similarly, a decreased aerobic capacity in miners was previously reported at an intensity of 175 W, representing a decreased maximal intensity of ~15% after 31 months of CIHH exposure in subjects evaluated at sea level (Richalet et al., 2002). Reduced HR was also explained by the downregulation of β-adrenergic receptors, upregulation of muscarinic receptors (Richalet et al., 1992), and a detraining effect of exposure to hypoxia and/or being excessively sedentary (Richalet et al., 2002). We considered that the lower VO₂ max values we observed in the present study could be due to a significant FM. However, when we calculated VO₂ max/LBM (kg), values of VO₂ max were enhanced but the percentage of change in VO₂ max at an altitude of 1,600 and 2,500 m compared to sea level was maintained (Table 4). This evidence suggests that the fall in VO₂ max is due to a lower aerobic capacity as a result of sedentarism, rather than an increase in the fatty mass in our population.

We found that work capacity, HR, and VE with a decreased VO₂ max is maintained at moderate altitude, suggesting that work efficiency is maintained. Higher prevalence of overweight-obesity, BF% and WC, and sedentarism in all miner populations are evidence of cardiometabolic risk that is not related to altitude. However, increased hsCRP levels were associated with altitudes of 1,600 and 2,500 m.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.