Reference equations for peak oxygen uptake for treadmill cardiopulmonary exercise tests based on the NHANES lean body mass equations, a FRIEND registry study

Everton J Santana^{1

2

3}, Daniel Seung Kim^{1

2

4

5}, Jeffrey W Christle^{1

4}, Nicholas Cauwenberghs³, Bettia E Celestin^{2

6}, Jason V Tso^{1

4}, Matthew T Wheeler^{1

2

4}, Euan A Ashley^{1

2

4

5}, James E Peterman⁷, Christopher Gardner⁸, Ross Arena⁹, Matthew Harber¹⁰, Leonard A Kaminsky⁸, Tatiana Kuznetsova³, Jonathan N Myers¹¹, Francois Haddad^{1

2

4}

Affiliations

¹ Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.
² Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA.
³ Research Unit Hypertension and Cardiovascular Epidemiology, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
⁴ Wu Tsai Human Performance Alliance, Stanford University, Stanford, CA, USA.
⁵ Center for Digital Health, Stanford University, Stanford, CA, USA.
⁶ Division of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
⁷ Fisher Institute of Health and Well-Being, College of Health, Ball State University, Muncie, Indiana.
⁸ Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, USA.
⁹ Department of Physical Therapy, College of Applied Science, University of Illinois Chicago, Chicago.
¹⁰ Clinical Exercise Physiology Laboratory, College of Health, Ball State University, Muncie, Indiana.
¹¹ Division of Cardiology, Veterans Affairs Palo Alto Healthcare System and Stanford University, Palo Alto, CA, USA.

PMID: 39920345
DOI: 10.1093/eurjpc/zwaf045

Reference equations for peak oxygen uptake for treadmill cardiopulmonary exercise tests based on the NHANES lean body mass equations, a FRIEND registry study

Everton J Santana et al. Eur J Prev Cardiol. 2025.

. 2025 Feb 7:zwaf045.

doi: 10.1093/eurjpc/zwaf045. Online ahead of print.

Authors

Affiliations

¹ Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.
² Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA.
³ Research Unit Hypertension and Cardiovascular Epidemiology, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
⁴ Wu Tsai Human Performance Alliance, Stanford University, Stanford, CA, USA.
⁵ Center for Digital Health, Stanford University, Stanford, CA, USA.
⁶ Division of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
⁷ Fisher Institute of Health and Well-Being, College of Health, Ball State University, Muncie, Indiana.
⁸ Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, USA.
⁹ Department of Physical Therapy, College of Applied Science, University of Illinois Chicago, Chicago.
¹⁰ Clinical Exercise Physiology Laboratory, College of Health, Ball State University, Muncie, Indiana.
¹¹ Division of Cardiology, Veterans Affairs Palo Alto Healthcare System and Stanford University, Palo Alto, CA, USA.

PMID: 39920345
DOI: 10.1093/eurjpc/zwaf045

Abstract

Aims: Cardiorespiratory fitness (CRF), measured by peak oxygen uptake (VO2peak), is a strong predictor of mortality. Despite its widespread clinical use, current reference equations for VO2peak show distorted calibration in obese individuals. Using data from the Fitness Registry and the Importance of Exercise National Database (FRIEND), we sought to develop novel reference equations for VO2peak better calibrated for overweight/obese individuals - in both males and females, by considering body composition metrics.

Methods: Graded treadmill tests from 6,836 apparently healthy individuals were considered in data analysis. We used the National Health and Nutrition Examination Survey equations to estimate lean body mass (eLBM) and body fat percentage (eBF). Multivariable regression was used to determine sex-specific equations for predicting VO2peak considering age terms, eLBM and eBF.

Results: The resultant equations were expressed as VO2peak (male) = 2633.4 + 48.7✕eLBM (kg) - 63.6✕eBF (%) - 0.23✕Age2 (R2=0.44) and VO2peak (female) = 1174.9 + 49.4✕eLBM (kg) - 21.7✕eBF (%) - 0.158✕Age2 (R2=0.53). These equations were well-calibrated in subgroups based on sex, age and body mass index (BMI), in contrast to the Wasserman equation. In addition, residuals for the percent-predicted VO2peak (ppVO2) were stable over the predicted VO2peak range, with low CRF defined as < 70% ppVO2 and average CRF defined between 85-115%.

Conclusions: The derived VO2peak reference equations provided physiologically explainable and were well-calibrated across the spectrum of age, sex and BMI. These equations will yield more accurate VO2peak evaluation, particularly in obese individuals.

Keywords: allometry; cardiorespiratory fitness; exercise testing; lean body mass; peak oxygen uptake; reference equations.

Plain language summary

In this work, we derived novel physiology-based reference equations for peak oxygen uptake, the gold-standard measurement of cardiorespiratory fitness, generating explainable models that account for differences in sex, age and body mass index. In our models, we adjusted for body composition, using estimates for lean body mass and body fat previously validated in the NHANES data. The derived equations for peak oxygen uptake are significantly improved across all studied populations, but particularly demonstrated improved results in obese women. These novel reference equations will yield more accurate evaluation of peak oxygen uptake. Given the importance of peak oxygen uptake in assessing overall cardiovascular health, our newly derived models will improve identification and longitudinal assessment of patients at risk for adverse cardiovascular outcomes, across the spectrum of body composition.

© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.

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Reference equations for peak oxygen uptake for treadmill cardiopulmonary exercise tests based on the NHANES lean body mass equations, a FRIEND registry study

Affiliations

Reference equations for peak oxygen uptake for treadmill cardiopulmonary exercise tests based on the NHANES lean body mass equations, a FRIEND registry study

Authors

Affiliations

Abstract

Plain language summary

LinkOut - more resources

Full Text Sources