Limb- and sex-specific determinants of vascular function assessed by flow-mediated dilation and passive limb movement

Assessing regional vascular function is crucial for understanding systemic cardiovascular health. This study primarily investigated whether flow-mediated dilation (FMD) and passive limb movement (PLM) yield congruent, interchangeable patterns across the upper limbs (ULs) and lower limbs (LLs). Secondarily, we evaluated sex-specific influences on these regional vascular relationships. Twenty healthy individuals (10 males and 10 females) underwent brachial and popliteal FMD, alongside axillary and femoral PLM, in a counterbalanced single session. Baseline diameters, FMD%, allometrically scaled FMD, and blood flow (BF) PLM parameters [peakBF, ΔpeakBF, area under the curve (AUC)] were analyzed. Regarding our primary aim, FMD% was significantly higher in UL than LL (7.7 ± 2.9% vs. 4.9 ± 1.8%; P = 0.002) and was not correlated between limbs (r = 0.11, P = 0.650). However, when analyzed using an allometric mixed model with baseline diameter as a covariate, this limb difference was no longer significant (P = 0.334). PLM ΔpeakBF was lower in UL than LL (ΔUL - LL = -68.3%; P < 0.001) but showed significant interlimb correlations (r = 0.50, P = 0.024). No limb × sex interaction was found for FMD% (P = 0.889) or allometric FMD% (P = 0.815). However, a significant limb × sex interaction emerged for PLM AUC (P < 0.001), driven by a higher absolute AUC in the LL for males (P < 0.001) and a higher volume-normalized AUC in the UL for females (P = 0.003). In conclusion, brachial and popliteal FMD are not interchangeable, providing complementary, region-specific information heavily influenced by vessel size, and FMD% is not affected by sex. PLM_UL and PLM_LL provide partially convergent but not equivalent information, warranting caution when comparing limbs, particularly when sex is a variable of interest.NEW & NOTEWORTHY This study directly compares flow-mediated dilation and passive limb movement across upper and lower limbs, providing novel insight into limb-specific vascular function. Flow-mediated dilation and passive limb movement are not interchangeable between limbs, impacting future experimental and clinical evaluation. Vascular function differs between sexes for passive limb movement, highlighting the need to consider sex-specific effects in study design.