Previous studies have indicated low-Hb adaptation to high altitude in Tibetans [1,2,3,4,5, 10, 18,19,20,21,22]. In the present study, we present physiological data of hemodynamic parameters (focusing primarily on SpO2) and individual variation and sex differences in isolated Tibetan highlanders living in Tsarang village.
The present study found no significant difference in SpO2 between men and women (Table 1). Beall et al. [23] reported lower SpO2 in male than female Tibetans living at an altitude of 3800–4200 m (mean SpO2: 90.2% at 3800 m, 89.2% at 3850 m, 88.7% at 4065 m, 88.9% at 4200 m) and sex differences in SpO2 tended to be greater at higher altitudes. SpO2 was relatively higher (92.4% at 3570 m) in the present study, and a similar study reported no sex differences in Tibetans at 3658 m [24]. Accordingly, sex differences in SpO2 might not be apparent in the Tibetan population at altitudes below 3700 m.
Higher Hb and blood pressure in men compared with women have been reported in a sea-level environment [25,26,27]. Similarly, Hb and SBP were both significantly higher in men than in women in the present study (Table 1), consistent with the result for Hb reported in a previous study of Tibetan and Andean highlanders [3]. These results suggest that the same sex differences in Hb and SBP are present in both highlanders and lowlanders.
The present results found no significant correlation between SpO2 and heart rate in men, but that SpO2 negatively correlated to heart rate in women (Fig. 1, Table 2). In women, multiple regression analysis showed that lower SpO2 was significantly correlated with higher heart rate after adjusting for covariates (Table 3). Heart rate decreases after long-term high-altitude exposure [28]; however, the present results indicate that lower SpO2 potentially evoked a higher heart rate for greater oxygen delivery even in Tibetan highlanders, and especially in women. This sex difference may indicate that in the case of higher Hb in men than women and higher blood flow for oxygen delivery in Tibetans [29, 30], lower SpO2 is not necessary to evoke a higher heart rate in men. Thus, although the association between SpO2 and heart rate is similar between Tibetan men and women, further studies that add men’s data and blood flow measurements are required to assess this complex association.
In men, multiple regression analysis revealed that lower SpO2 was marginally correlated with lower Hb after adjusting for covariates (Table 3). In contrast, in women, lower SpO2 was significantly correlated with higher Hb after adjusting for covariates (Table 3). This negative correlation in women is reasonable because higher Hb enables higher oxygen delivery, even if SpO2 is lower. However, as there was a weak positive correlation between SpO2 and Hb in men, the inverse result is difficult to explain. As men had higher Hb than women, this positive correlation might indicate better hemodynamic adaptation to high altitude or increasing pulmonary arterial pressure in men. Contrary to the present results, Beall et al. [3] reported a negative correlation between SpO2 and Hb in Tibetan men but not in Tibetan women at 3800–4065 m. This inconsistency in sex differences might be due to inconsistency in the studied high-altitude environments and population differences between TAR (Tibet autonomous region) and Tibetans living in Tsarang. In addition, Beall et al. [23] also suggested the effect of age and sex interactions on SpO2 in Tibetans in TAR, and they also recently reported aging changes of SpO2 in Tibetan women in Tsarang [31]. Similarly, our results also showed an aging effect of SpO2, in men and overall (Table 3). Taken together, the present results and those of previous studies suggest sex differences in hemodynamics and SpO2 in Tibetan highlanders of Tsarang. Further studies are necessary to clarify the biological mechanism of this complex association in greater detail.
We have previously reported sex and individual differences in hemodynamics and SpO2 in young Andean highlanders in Bolivia (altitude, 3700–4000 m) in a study of a similar duration, using the same protocol [14]. SpO2 was higher in the present study (mean [95 % CI], 92.4% [92.0–92.8%]) compared with the Andean highlanders (91% [90.0–91.0%]). Although previous studies have reported lower SpO2 in Tibetans than in Andeans at similar altitudes [1, 3], Tsarang is located at 3570 m and the environment is moderately hypoxic compared with Bolivia (3700–4000 m), which might be the reason why Tibetan in Tsarang could maintain higher SpO2.
Typically, among lowlanders, men have higher skin temperature and peripheral blood flow than women, in a thermoneutral environment [32, 33]. Another study found higher finger temperature in Andean men than in Andean women [14]. Interestingly, there was no significant sex difference in finger temperature in the present study, and it was slightly higher in Tibetans than in Andeans in our previous studies [14]. Previous studies have reported that Tibetan highlanders had high nitric oxide (NO) concentration and blood flow for oxygen delivery [29, 30], which suggests that Tibetan highlanders in Tsarang also have higher blood flow as a high-altitude adaptation, similar to other Tibetans. In addition, the mean (95% CI) Hb of Tibetans in the present study was 13.6 g/dl (13.1–14.0 g/dl), which is clearly lower than that of Andeans and almost equal to that of Japanese lowlanders measured using the same device [34]. This finding might indicate that Tibetans living in Tsarang have a low-Hb adaptation to high altitude; however, as some of the present individuals had higher Hb (≥17.0 g/dl) (Fig. 2), it is necessary to assess the mechanism for individual differences in more detail. In the total regression analysis, 22.3% of the variation in SpO2 was explained in men and 36.5% in women, but the remaining variation was unclear. Recent studies have reported that the physiological status of highlanders is affected by EPAS1 and EGLN1 genes [7, 8, 11, 18, 35,36,37]. The effect of these genetic variations and other underlying factors on individual variations requires further investigation.
The present study has several limitations. First, the results do not necessarily show a causal relationship because of the cross-sectional design of the study. Second, the sample size was limited and also information on other determinants (e.g., ventilation, nutritional status, or menstrual cycle) contributing to SpO2 was not obtained. Third, because Hb concentrations were estimated values, they are difficult to compare with values reported in other studies.