Both flow-mediated dilation and constriction are associated with changes in blood flow and shear stress: Two complementary perspectives on endothelial function

INTRODUCTION: Flow-mediated dilation (FMD) quantifies endothelium-dependent vasomotor responses to short-term increases in blood flow. Low-flow mediated vasoconstriction (L-FMC) has been more recently introduced as additional measure of endothelial function, and its relationship with changes in blood flow, cardiovascular risk factors and FMD ha. s been less well characterized. MATERIALS AND METHODS: We evaluated radial artery FMD and L-FMC along with the changes in blood flow and shear rate/stress in 584 patients with known or suspected coronary artery disease (72.9% men, mean age 67+/-11 years). Baseline blood flow and shear rate showed a modest association with radial artery FMD and L-FMC (R-2 = 0.04 and R-2 = 0.02, P < 0.0001). Resting diameter showed a stronger association with FMD but not with L-FMC (R-2 = 0.11, P < 0.0001 and R-2 = 0.005, P = 0.09). Analysis with generalized additive models showed that age, sex and presence and extent of coronary artery disease were strongly related to both endothelial function measures (P < 0.001 for both), but they explained only 12.4% and 10.1% of the variance in L-FMC and FMD. When the corresponding changes in blood flow were added to these statistical models, the % of variance explained raised to 20.4% and 17.7% for L-FMC and FMD. L-FMC was a strong predictor of FMD even after correction for the changes in blood flow. DISCUSSION: Changes in blood flow are the most important determinants of both L-FMC and FMD. These observations support the concept that both FMD and L-FMC measure endothelium-dependent, shear-induced, vasomotion.