Even small increases in residential altitude significantly elevated blood hemoglobin (Hb) and ferritin levels in young men living in Switzerland, according to a study published in Blood. Findings from this study, led by Kaspar Staub, MD, from the Zurich Center for Integrative Human Physiology, suggest that modest altitude elevations need to be taken into account when defining hemoglobin thresholds for anemia in populations that reside <1,500 meters above sea level (MASL).
The World Health Organization defines anemia as Hb levels of <12 g/dL in women and <13 g/dL in men, Dr. Staub explained to ASH Clinical News. “However, these levels do not account for many patient characteristics, including ethnicity, age, gender, socioeconomic situation, and residential altitude.” In this study, Dr. Staub and colleagues sought to examine the association between Hb levels and residential altitude in a large cohort of healthy young Swiss men who resided between 200 MASL and 2,000 MASL.
In this study, Dr. Staub and colleagues collected data between 2010 and 2012 from 110,810 men aged 18 to 21 years enrolled in the Swiss Armed Forces. A total of 71,798 men (64.8%) volunteered for blood testing with a hemoglobinometer to determine Hb concentrations.
Participants who volunteered to undergo blood testing lived at an average altitude of 543.5 MASL, with the majority (91.1%) residing between 300 and 900 MASL. Overall, the mean Hb concentration was 15.6 g/dL (range = 6.7-21.7 g/dL).
Just 178 of the participants (0.25%) had anemia, using a Hb threshold of <13.0 g/dL. The researchers observed that, as altitude increased, the prevalence of anemia defined by WHO criteria decreased.
As seen in the FIGURE, serum Hb concentrations mirrored the topography of Switzerland, creating what the researchers termed the country’s “hemoglobinography.” There was a 2.84% increase in the mean Hb concentrations of young men living below 300 MASL and those living above 1,800 MASL, from 15.5 g/dL to 15.9 g/dL. Hb concentrations rose significantly and in a stepwise fashion with each 300 MASL increase in altitude, the authors observed. However, there were no further increases between the altitude levels of 900 MASL to 1,199 MASL and 1,200 MASL to 1,499 MASL.
Serum ferritin levels, a marker for body iron stores, also significantly increased according to altitude in young men with normal Hb concentrations (<17.5 g/dL), normal C-reactive protein (<5.0 mg/L), and normal body mass index (18.5-24.9 kg/m2). The highest mean ferritin levels were observed in men who lived at high altitudes and had high Hb levels. In addition, mean ferritin levels increased with residential altitude within the five Hb quintile levels, suggesting mechanisms exist that increase iron stores based on altitude.
According to Dr. Staub, these data have no direct effect on patients treated in hospitals located at low altitudes, because the increases in Hb levels reported at these low altitudes are typically within the normal range. However, “these findings change when the patients are treated at higher altitudes, as in the Alps or in the Rockies,” he said. “On the other hand, when the threshold for anemia has to be defined for a given population, every increase in altitude has to be taken into consideration, which is especially true for patients living at low- to moderate-altitude areas (up to 2,500 meters), as we demonstrated in this study.”
When asked about the mechanisms behind the association between altitude and hemoglobin, Dr. Staub speculated that the body’s cellular oxygen sensor mechanism can detect subtle altitude changes through hypoxia-inducible factor-2 and prolylhydroxylase-2 activity. Evolution has adapted this sensing mechanism to increase red blood cell production for neuroprotection and neuroregeneration in conditions of relative hypoxia.
“For future research, we and others will focus on the mechanisms that allow such precise [regulation] of oxygenation,” he said. He speculated that the gut may sense oxygenation in an Hb-independent manner and regulate iron absorption.
A potential limitation of the study included the recruitment of a relatively ethnically homogenous group of Swiss volunteers.
Staub K, Haeusler M, Bender N, et al. Hemoglobin concentration of young men at residential altitudes between 200 and 2000m mirrors Switzerland’s topography. Blood. 2020 February 10. [Epub ahead of print]