What is the clinical evidence from this study?

Study design: Cohort. Population: Endothelial dysfunction and cardiovascular risk factors (n=164). Intervention: Aerobic exercise training. Primary outcome: Change in peak oxygen consumption (V̇O2peak) (MD 2.57, 95% CI 0.45-4.68, p=0.019).

What question did this study set out to answer?

This study aims to evaluate the impact of endothelial dysfunction on aerobic exercise benefits and cardiorespiratory fitness in middle-aged adults.

June 16, 2026Open Access

Effects of Aerobic Training on Cardiorespiratory Fitness in Middle Aged Adults with Endothelial Dysfunction

KKKarsten KönigsteinPreventive Cardiology TAThomas AngstCenter for Health, Exercise and Sport Sciences HCHélmi ChaabèneUniversity of Sfax

Key Result

Aerobic exercise training improved V̇O2peak by 2.57 ml/kg/min, but this improvement was significantly attenuated in participants with lower baseline endothelial function (p<0.001).

Key Points

This study aims to evaluate the impact of endothelial dysfunction on aerobic exercise benefits and cardiorespiratory fitness in middle-aged adults.
Randomized controlled trial with 30 middle-aged adults undergoing 8 weeks of supervised aerobic training.
Assessment included peak oxygen consumption, brachial-arterial flow-mediated dilation, and cardiovascular risk at baseline and follow-up.
Statistical analysis utilized multiple linear regression models to evaluate associations.
Aerobic training significantly improved peak oxygen consumption ( $$\dot{V}$$ O 2peak ), but the improvement was reduced in individuals with lower baseline baFMD (p < 0.001).
No significant moderating effect of baFMD on the relationship between age and $$\dot{V}$$ O 2peak was found (p = 0.254).

Study Design

Type

Cohort (n=164)

Randomization

Randomized

Multicenter

Structured PICO

Does pre-existing endothelial dysfunction attenuate the improvement of cardiorespiratory fitness in response to aerobic exercise in middle-aged adults?

Population

164 apparently healthy middle-aged adults (mean age 50.2 years, 40.9% female) with and without cardiovascular risk factors, of which 30 underwent an 8-week aerobic training intervention.

Intervention

8-week supervised aerobic training intervention (three sessions of 30 to 60 min per week, moderate- and high-intensity aerobic exercise, no resistance training)

Outcome

Effect of pre-existing endothelial dysfunction (brachial-arterial flow-mediated dilation [baFMD]) on the association between age and cardiorespiratory fitness (peak oxygen consumption [VO2peak]), and on the change in VO2peak in response to 8 weeks of aerobic exercise trainingsurrogate

Pre-existing endothelial dysfunction attenuates the improvement of cardiorespiratory fitness in response to aerobic exercise in middle-aged adults, suggesting exercise interventions should be implemented early in cardiovascular prevention.

Main Result

Mean Difference: 2.57 (95% CI 0.45–4.68)

p-value: p=0.019

Limitations

Inclusion of only male participants in the intervention prevents translation to the female population.
Considerable drop-out rate from the intervention (7 out of 30) due to the COVID pandemic.
Presentation of only full datasets without imputation at baseline.
Cross-sectional nature of the baseline data does not permit establishing causality.

Abstract

Abstract Objectives High cardiorespiratory fitness is a vital part of cardiovascular prevention in health and disease. However, the optimal age of aerobic exercise interventions is unclear and animal studies suggest a blunted effect of training on cardiorespiratory fitness with a priori endothelial dysfunction. This study aims to assess the effect of pre-existing endothelial dysfunction on the association between age and cardiorespiratory fitness as well as the change of the latter in response to 8 weeks of aerobic exercise training. Methods Cardiorespiratory fitness (peak oxygen consumption V̇ O 2peak), brachial-arterial flow-mediated dilation (baFMD) and cardiovascular risk were assessed in 164 apparently healthy disease-free middle-aged adults with and without pre-existing endothelial dysfunction and cardiovascular risk factors (n = 36 arterial hypertension, n = 59 obesity, n = 118 dyslipidemia, n = 15 diabetes mellitus type II, n = 30 chronic inflammation). 30 of them underwent a randomized-controlled and supervised 8-week aerobic training intervention followed by a second assessment of V̇ O 2peak, baFMD and cardiovascular risk. Multiple linear regression models were used to address the study aims. Results No clear evidence was found for a moderating effect of baFMD on the relationship of V̇ O 2peak with age (F (3, 151) = 1. 37, p = 0. 254). The improvement of V̇ O 2peak by aerobic exercise was significantly attenuated with lower baseline baFMD (F (3, 5. 33) = 43. 13, df = 3, p < 0. 001). Conclusions The results provide evidence in middle-aged adults for an attenuated response of cardiorespiratory fitness to aerobic exercise in the presence of endothelial dysfunction, advocating for the early involvement of aerobic exercise within primary prevention of cardiovascular diseases and low cardiorespiratory fitness. Trial Registration TRN: (COmPLETE Health cohort NCT03986892 and VascuFit cohort NCT05235958).

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