The current standard measure of cardiorespiratory fitness introduces confounding by body mass: the DR's EXTRA study

OBJECTIVE: Cardiorespiratory fitness is currently estimated by dividing maximal oxygen consumption (VO2max) by body weight (per-weight standard). However, the statistically correct way to neutralize the effect of weight on VO2max in a given population is adjustment for body weight by regression techniques (adjusted standard). Our objective is to quantify the bias introduced by the per-weight standard in a population distributed across different categories of body mass. DESIGN: This is a cross-sectional study. SUBJECTS AND METHODS: Baseline measures from participants of the Dose-Responses to Exercise Training Study (DR's EXTRA), 635 men (body mass index (BMI): 19-47 kgm(-2)) and 638 women (BMI: 16-49 kgm(-2)) aged 57-78 years who performed oral glucose tolerance tests and maximal exercise stress tests with direct measurement of VO2max. We compare the increase in VO2max implied by the per-weight standard with the real increase of VO2max per kg body weight. A linear logistic regression model estimates odds for abnormal glucose metabolism (either impaired fasting glycemia or impaired glucose tolerance or Type 2 diabetes) of the least-fit versus most-fit quartile according to both per-weight standard and adjusted standard. RESULTS: The per-weight standard implies an increase of VO2max with 20.9 ml min(-1) in women and 26.4 ml min(-1) in men per additional kg body weight. The true increase per kg is only 7.0 ml min(-1) (95% confidence interval: 5.3-8.8) and 8.0 ml min(-1) (95% confidence interval: 5.3-10.7), respectively. Risk for abnormal glucose metabolism in the least-fit quartile of the population is overestimated by 52% if the per-weight standard is used. CONCLUSIONS: In comparisons across different categories of body mass, the per-weight standard systematically underestimates cardiorespiratory fitness in obese subjects. Use of the per-weight standard markedly inflates associations between poor fitness and co-morbidities of obesity.