The relationship between hemoglobin and <math xmlns="http://www.w3.org/1998/Math/MathML"> <mrow> <mover accent="true"> <mi mathvariant="bold">V</mi> <mo>˙</mo> </mover> <mo>⁢</mo> <msub> <mi mathvariant="bold">O</mi> <mn mathvariant="bold">2</mn> </msub> <mo>⁢</mo> <mi mathvariant="bold">m</mi> <mo>⁢</mo> <mi mathvariant="bold">a</mi> <mo>⁢</mo> <mi mathvariant="bold">x</mi> </mrow> </math>: A systematic review and meta-analysis.

Abstract

There is widespread agreement about the key role of hemoglobin for oxygen transport. Both observational and interventional studies have examined the relationship between hemoglobin levels and maximal oxygen uptake (<math xmlns="http://www.w3.org/1998/Math/MathML"> <mrow> <mover accent="true"> <mi mathvariant="normal">V</mi> <mo>˙</mo> </mover> <mo>⁢</mo> <msub> <mi mathvariant="normal">O</mi> <mn>2</mn> </msub> <mo>⁢</mo> <mi mathvariant="normal">m</mi> <mo>⁢</mo> <mi mathvariant="normal">a</mi> <mo>⁢</mo> <mi mathvariant="normal">x</mi> </mrow> </math>) in humans. However, there exists considerable variability in the scientific literature regarding the potential relationship between hemoglobin and <math xmlns="http://www.w3.org/1998/Math/MathML"> <mrow> <mover accent="true"> <mi mathvariant="normal">V</mi> <mo>˙</mo> </mover> <mo>⁢</mo> <msub> <mi mathvariant="normal">O</mi> <mn>2</mn> </msub> <mo>⁢</mo> <mi mathvariant="normal">m</mi> <mo>⁢</mo> <mi mathvariant="normal">a</mi> <mo>⁢</mo> <mi mathvariant="normal">x</mi> </mrow> </math>. Thus, we aimed to provide a comprehensive analysis of the diverse literature and examine the relationship between hemoglobin levels (hemoglobin concentration and mass) and <math xmlns="http://www.w3.org/1998/Math/MathML"> <mrow> <mover accent="true"> <mi mathvariant="normal">V</mi> <mo>˙</mo> </mover> <mo>⁢</mo> <msub> <mi mathvariant="normal">O</mi> <mn>2</mn> </msub> <mo>⁢</mo> <mi mathvariant="normal">m</mi> <mo>⁢</mo> <mi mathvariant="normal">a</mi> <mo>⁢</mo> <mi mathvariant="normal">x</mi> </mrow> </math> (absolute and relative <math xmlns="http://www.w3.org/1998/Math/MathML"> <mrow> <mover accent="true"> <mi mathvariant="normal">V</mi> <mo>˙</mo> </mover> <mo>⁢</mo> <msub> <mi mathvariant="normal">O</mi> <mn>2</mn> </msub> <mo>⁢</mo> <mi mathvariant="normal">m</mi> <mo>⁢</mo> <mi mathvariant="normal">a</mi> <mo>⁢</mo> <mi mathvariant="normal">x</mi> </mrow> </math>) among both observational and interventional studies. A systematic search was performed on December 6th, 2021. The study procedures and reporting of findings followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Article selection and data abstraction were performed in duplicate by two independent reviewers. Primary outcomes were hemoglobin levels and <math xmlns="http://www.w3.org/1998/Math/MathML"> <mrow> <mover accent="true"> <mi mathvariant="normal">V</mi> <mo>˙</mo> </mover> <mo>⁢</mo> <msub> <mi mathvariant="normal">O</mi> <mn>2</mn> </msub> <mo>⁢</mo> <mi mathvariant="normal">m</mi> <mo>⁢</mo> <mi mathvariant="normal">a</mi> <mo>⁢</mo> <mi mathvariant="normal">x</mi> </mrow> </math> values (absolute and relative). For observational studies, meta-regression models were performed to examine the relationship between hemoglobin levels and <math xmlns="http://www.w3.org/1998/Math/MathML"> <mrow> <mover accent="true"> <mi mathvariant="normal">V</mi> <mo>˙</mo> </mover> <mo>⁢</mo> <msub> <mi mathvariant="normal">O</mi> <mn>2</mn> </msub> <mo>⁢</mo> <mi mathvariant="normal">m</mi> <mo>⁢</mo> <mi mathvariant="normal">a</mi> <mo>⁢</mo> <mi mathvariant="normal">x</mi> </mrow> </math> values. For interventional studies, meta-analysis models were performed to determine the change in <math xmlns="http://www.w3.org/1998/Math/MathML"> <mrow> <mover accent="true"> <mi mathvariant="normal">V</mi> <mo>˙</mo> </mover> <mo>⁢</mo> <msub> <mi mathvariant="normal">O</mi> <mn>2</mn> </msub> <mo>⁢</mo> <mi mathvariant="normal">m</mi> <mo>⁢</mo> <mi mathvariant="normal">a</mi> <mo>⁢</mo> <mi mathvariant="normal">x</mi> </mrow> </math> values (standard paired difference) associated with interventions designed to modify hemoglobin levels or <math xmlns="http://www.w3.org/1998/Math/MathML"> <mrow> <mover accent="true"> <mi mathvariant="normal">V</mi> <mo>˙</mo> </mover> <mo>⁢</mo> <msub> <mi mathvariant="normal">O</mi> <mn>2</mn> </msub> <mo>⁢</mo> <mi mathvariant="normal">m</mi> <mo>⁢</mo> <mi mathvariant="normal">a</mi> <mo>⁢</mo> <mi mathvariant="normal">x</mi> </mrow> </math>. Meta-regression models were then performed to determine the relationship between a change in hemoglobin levels and the change in <math xmlns="http://www.w3.org/1998/Math/MathML"> <mrow> <mover accent="true"> <mi mathvariant="normal">V</mi> <mo>˙</mo> </mover> <mo>⁢</mo> <msub> <mi mathvariant="normal">O</mi> <mn>2</mn> </msub> <mo>⁢</mo> <mi mathvariant="normal">m</mi> <mo>⁢</mo> <mi mathvariant="normal">a</mi> <mo>⁢</mo> <mi mathvariant="normal">x</mi> </mrow> </math> values. Data from 384 studies (226 observational studies and 158 interventional studies) were examined. For observational data, there was a positive association between absolute <math xmlns="http://www.w3.org/1998/Math/MathML"> <mrow> <mover accent="true"> <mi mathvariant="normal">V</mi> <mo>˙</mo> </mover> <mo>⁢</mo> <msub> <mi mathvariant="normal">O</mi> <mn>2</mn> </msub> <mo>⁢</mo> <mi mathvariant="normal">m</mi> <mo>⁢</mo> <mi mathvariant="normal">a</mi> <mo>⁢</mo> <mi mathvariant="normal">x</mi> </mrow> </math> and hemoglobin levels (hemoglobin concentration, hemoglobin mass, and hematocrit (P<0.001 for all)). Prespecified subgroup analyses demonstrated no apparent sex-related differences among these relationships. For interventional data, there was a positive association between the change of absolute <math xmlns="http://www.w3.org/1998/Math/MathML"> <mrow> <mover accent="true"> <mi mathvariant="normal">V</mi> <mo>˙</mo> </mover> <mo>⁢</mo> <msub> <mi mathvariant="normal">O</mi> <mn>2</mn> </msub> <mo>⁢</mo> <mi mathvariant="normal">m</mi> <mo>⁢</mo> <mi mathvariant="normal">a</mi> <mo>⁢</mo> <mi mathvariant="normal">x</mi> </mrow> </math> (standard paired difference) and the change in hemoglobin levels (hemoglobin concentration (P<0.0001) and hemoglobin mass (P = 0.006)). These findings suggest that <math xmlns="http://www.w3.org/1998/Math/MathML"> <mrow> <mover accent="true"> <mi mathvariant="normal">V</mi> <mo>˙</mo> </mover> <mo>⁢</mo> <msub> <mi mathvariant="normal">O</mi> <mn>2</mn> </msub> <mo>⁢</mo> <mi mathvariant="normal">m</mi> <mo>⁢</mo> <mi mathvariant="normal">a</mi> <mo>⁢</mo> <mi mathvariant="normal">x</mi> </mrow> </math> values are closely associated with hemoglobin levels among both observational and interventional studies. Although our findings suggest a lack of sex differences in these relationships, there were limited studies incorporating females or stratifying results by biological sex.