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 (UL) and lower limbs (LL). Secondarily, we evaluated sex-specific influences on these regional vascular relationships. Twenty healthy individuals (10 males, 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 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 inter-limb correlations (r=0.50, p=0.024). No limb x sex interaction was found for FMD% (p=0.889) or allometric FMD% (p=0.815). However, a significant limb x 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. PLMUL and PLMLL provide partially convergent but not equivalent information, warranting caution when comparing limbs, particularly when sex is a variable of interest.