Diastolic Shear Stress Research Articles

Impaired flow-mediated dilatation response in uncomplicated Type 1 diabetes mellitus: influence of shear stress and microvascular reactivity

Impaired FMD (flow-mediated dilatation) has traditionally been recognized as an indirect marker of NO bioactivity, occurring in disease states such as DM (diabetes mellitus). Endothelium-dependent FMD is a homoeostatic response to short-term increases in local shear stress. Microvascular dysfunction in DM influences blood flow velocity patterns. We explored the determinants of the FMD response in relation to evoked DSS (diastolic shear stress) and forearm microcirculation haemodynamics by quantifying changes in Doppler flow velocity waveforms between groups. Forty patients with uncomplicated Type1 DM and 32 controls underwent B-mode and Doppler ultrasound scanning to interrogate the brachial artery. Postischaemic Doppler velocity spectral envelopes were recorded and a wavelet-based time-frequency spectral analysis method was employed to track change in distal microcirculatory haemodynamics. No difference in baseline brachial artery diameter was evident between the groups (4.15 compared with 3.94 mm, P=0.23). FMD was significantly impaired in patients with Type1 DM (3.95 compared with 7.75%, P<0.001). Endothelium-independent dilatation in response to GTN (glyceryl trinitrate) was also significantly impaired (12.07 compared with 18.77%, P<0.001). DSS (dyn/cm2) was significantly reduced in the patient group (mean 20.19 compared with 29.5, P=0.001). Wavelet interrogation of postischaemic flow velocity waveforms identified significant differences between groups. In conclusion, DSS, microcirculatory function and endothelium-independent vasodilatation in response to GTN are important determinants that impact on the magnitude of FMD response and are impaired in patients with Type1 DM. Impaired FMD response is multifactorial in origin and cannot be attributed solely to a diminished NO bioavailability.

Effect of pioglitazone on endothelial function in impaired glucose tolerance

Flow-mediated dilation (FMD) is a surrogate marker of endothelial function, which has been proposed as a barometer of vascular health. Impaired microvascular response to reactive hyperaemia is thought to be the mechanism behind reduced shear stress and subsequently impaired FMD, which has been associated with cardiovascular events. This study aims to assess the effect of pioglitazone on the vasculature of patients with impaired glucose tolerance (IGT). Forty IGT patients with no cardiovascular disease were compared with 24 healthy age- and sex-matched controls. Endothelial function was assessed using FMD of the brachial artery. Adiponectin (ADN) levels were measured and insulin sensitivity was calculated using homeostasis model assessment of insulin resistance (HOMA-IR). A randomised double-blind placebo-controlled trial of the IGT subjects was then performed, with subjects receiving either pioglitazone 30 mg od or matched placebo for 12 weeks before the measurements were repeated. The IGT subjects had a significantly impaired FMD compared with the controls (p < 0.001). Diastolic shear stress (DSS) was also significantly reduced in IGT (p = 0.04). High molecular weight (HMW) ADN was significantly lower in the IGT group than in controls (p = 0.03). On analysis of the IGT group after 12 weeks treatment, FMD was significantly increased in the pioglitazone group compared with placebo (p = 0.03) as was endothelium-independent dilation (EID) (p = 0.03). A significant increase in total ADN (p < 0.001), HMW ADN (p < 0.001) and HMW/total ratio (p = 0.001) occurred in the pioglitazone group compared with placebo. Pioglitazone improved endothelial function in IGT. Treatment with pioglitazone may reduce the risk of cardiovascular disease in this patient group.

Microcirculatory Hemodynamics and Endothelial Dysfunction in Systemic Lupus Erythematosus

Impaired flow-mediated dilation (FMD) occurs in disease states associated with atherosclerosis, including SLE. The primary hemodynamic determinant of FMD is wall shear stress, which is critically dependent on the forearm microcirculation. We explored the relationship between FMD, diastolic shear stress (DSS), and the forearm microcirculation in 32 patients with SLE and 19 controls. DSS was calculated using (mean diastolic velocity x 8 x blood viscosity)/baseline brachial artery diameter. Doppler velocity envelopes from the first 15 seconds of reactive hyperemia were analyzed for resistive index (RI), and interrogated in the frequency domain to assess forearm microvascular hemodynamics. FMD was significantly impaired in SLE patients (median, 2.4%; range, -2.1% to 10.7% versus median 5.8%; range, 1.9% to 14%; P<0.001). DSS (dyne/cm2) was significantly reduced in SLE patients (median, 18.5; range, 3.9 to 34.0 versus median 21.8; range, 14.1 to 58.7; P=0.037). A strong correlation between FMD and DSS, r(s)=0.65, P=0.01 was found. Postischemic RI was not significantly different between the 2 groups; however, there were significant differences in the power-frequency spectrums of the Doppler velocity envelopes (P<0.05). These data suggest that in SLE, altered structure and function of the forearm microcirculation contributes to impaired FMD through a reduction in shear stress stimulus.

Flow-Mediated Dilation: Just a Marker of Local Shear Stress?

To the Editor: We read with interest the article by Mitchell et al1 and agree that flow-mediated dilation (FMD%) response may be partially explained by shear stress (diastolic shear stress [DSS]) or flow changes.2 However, this does not necessarily mean that risk factors do not influence the vascular response. Indeed, Megnien et al3 showed that shear stress reduction provokes different diameter changes in hypercholesterolemic compared with normal subjects. Moreover, experiments performed by our group (M. Laclaustra et al, unpublished data, 2003) on healthy male subjects showed that HDL-cholesterol level was the strongest predictor of FMD% among all lipid variables considered in the study. This finding was actually apparent after controlling by average flow velocity during the first minute of hyperemia (model’s R 2=0.173). Thus FMD% may have a greater sensitivity to detect the effects of risk factor modification than shear stress, as shown in previous articles, including the one incorporating the very first description of the flow-mediated dilation technique.4 Indeed, in those reports, significant differences among groups were found for FMD% values but not for hyperemic flow values. Mitchell et al1 rightly point out that the fact that brachial artery diameter was included in the equations used for calculations of FMD% …