Association Between Cardiorespiratory Fitness and Non-invasively Assessed Macrovascular Reactivity Across the Cardiovascular Risk Spectrum

Flow‑mediated slowing (FMS) is a user‑friendly, non‑invasive measure of macrovascular reactivity based on the decline in brachial–radial pulse wave velocity (PWV) during reactive hyperaemia. To evaluate the clinical utility of FMS in cardiovascular (CV) risk stratification we examined its association with cardiorespiratory fitness (CRF) across the CV risk spectrum. This cross-sectional analysis included 284 adults with or without CV risk factors. FMS was analysed continuously as relative PWV changes at 30-second intervals, and categorically as abnormal peak FMS and response. CRF was quantified as peak oxygen uptake (VO₂peak), including percentage of predicted VO₂peak (ppVO₂peak). Associations were explored using correlation and multivariable regression, stratified by CV risk status and sex. Of 284 participants (61 ± 11 years; 44% women), 237 had ≥ 1 CV risk factor. In apparently healthy individuals, greater PWV change correlated with higher VO₂peak (p < 0.05), a pattern not observed in at-risk participants. Multivariable models showed that greater PWV reductions were independently associated with higher ppVO₂peak in the full cohort (p < 0.01) and at-risk subgroup (p < 0.05), with the strongest associations with both VO₂peak and ppVO₂peak seen in healthy individuals (p < 0.01 for most intervals). An abnormally low FMS response was associated with lower VO₂peak/kg and ppVO₂peak (p < 0.05). Associations appeared stronger in women (p < 0.01 for most intervals), though sex interactions were not significant. Better macrovascular reactivity, as assessed by FMS, was associated with higher CRF, particularly in women and apparently healthy individuals. These findings highlight FMS as a promising, scalable tool for CV risk stratification.