Local Shear Stress and Brachial Artery Flow-Mediated Dilation

Abstract

Abstract-Endothelium-dependent flow-mediated dilation is a homeostatic response to short-term increases in local shear stress. Flow-mediated dilation of the brachial artery in response to postischemic reactive hyperemia is impaired in patients with cardiovascular disease risk factors and may reflect local endothelial dysfunction in the brachial artery. However, previous studies have largely neglected the effect of risk factors on evoked shear stress, which is the stimulus for dilation. We evaluated brachial artery percent dilation and evoked diastolic shear stress during reactive hyperemia using high-resolution ultrasound and Doppler in 2045 participants (1107 women, mean age 61 years) in the Framingham Offspring Study. In age-and sex-adjusted models, baseline and hyperemic shear stress were related to brachial artery percent dilation. In stepwise multivariable analyses examining clinical correlates of percent dilation (without shear stress in the model), age, sex, mean arterial pressure, pulse pressure, heart rate, body mass index, lipid medication use, and hormone replacement therapy were related to percent dilation (R 2 ϭ0.189; PϽ0.001). When hyperemic shear stress was incorporated, the overall R 2 improved (R 2 ϭ0.335; PϽ0.001), but relationships between risk factors and percent dilation were attenuated (age and mean arterial pressure) or no longer significant (all others). In contrast, risk factors were related to baseline and hyperemic shear stress in multivariable analyses. Evoked hyperemic shear stress is a major correlate of brachial artery flow-mediated dilation. The associations between many risk factors and brachial artery flow-mediated dilation may be attributable to reduced stimulus for dilation rather than impaired local conduit artery response during hyperemia. Key Words: endothelium Ⅲ microcirculation Ⅲ risk factors L ocal shear stress (SS) has important short-and long-term effects on the vascular endothelium that are relevant to atherogenesis. 1,2 Under normal conditions, the vascular endothelium responds to short-term increases in flow by releasing NO and other endothelium-dependent relaxing factors that dilate the artery and reduce SS toward normal. 3 Flow-mediated dilation (FMD) is impaired in atherosclerotic coronary arteries, 4 although the response is maintained in patients with hypercholesterolemia and angiographically normal arteries. 5 FMD has been studied noninvasively in the brachial artery by using reactive hyperemia after a short period of forearm ischemia as the flow stimulus and evaluating percentage increase in brachial artery diameter (FMD%). 6 Brachial artery FMD% is impaired in patients with cardiovascular disease risk factors (CRFs) or coronary atherosclerosis. 7 Reactive hyperemia largely reflects dilation of resistance vessels by ischemia-induced production of vasodilators including NO. 8 Although not widely appreciated, some studies have demonstrated a reduction in reactive hyperemia in patients with CRFs 9,10 or coronary artery disease. 7 Because reactive hyperemia is th...

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“…Briefly, high‐resolution ultrasound was used to measure brachial artery diameter before and 1 minute after induction of hyperemic response by 5‐minute cuff occlusion of the upper arm. Doppler flow signals were recorded from the brachial artery before and after cuff occlusion to measure reactive hyperemia 21. Afterwards, we measured nitroglycerin‐mediated dilatation, which reflects non–endothelium‐dependent dilatation.…”

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“…In a large cohort from Framingham, it was demonstrated that hyperemicinduced shear stress was an important predictor of brachial FMD. In addition, risk factors diminished the magnitude of shear stress, suggesting that a reduced stimulus explains the diminution in endothelial function in subjects with cardiovascular risk factors (122).…”

“…Arterial stiffness has also been demonstrated to be related to brachial artery FMD vasodilation in a recent small study (121). And finally, a recently published study by Mitchell et al (122) has challenged our thinking about the effect of risk factors on brachial endothelial function. In a large cohort from Framingham, it was demonstrated that hyperemicinduced shear stress was an important predictor of brachial FMD.…”