Microcirculatory Hemodynamics and Endothelial Dysfunction in Systemic Lupus Erythematosus

Abstract

Objective-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. Methods and Results-DSS was calculated using (mean diastolic velocityϫ8ϫblood 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, Ϫ2.1% to 10.7% versus median 5.8%; range, 1.9% to 14%; PϽ0.001). DSS (dyne/cm 2 ) 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; Pϭ0.037). A strong correlation between FMD and DSS, r s ϭ0.65, Pϭ0.01 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 (PϽ0.05). Conclusions-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. Key Words: eigenvector Ⅲ flow-mediated dilation Ⅲ microcirculation Ⅲ shear stress Ⅲ systemic lupus erythematosus S ystemic lupus erythematosus (SLE) is the archetypal autoimmune disease, with a wide range of clinical manifestations. Among the clinical challenges of SLE, one of the most compelling is the high incidence of atherosclerosis in young women. In 1976, Urowitz et al showed a bimodal mortality pattern in SLE, with late deaths (comprising 45%) attributed to myocardial infarction. 1 Women with SLE have a high prevalence of coronary artery disease (CAD) 2 and an incidence of myocardial infarction up to 50 times higher than age-matched normals. 3 Classical risk factors are similar to those in the general population, 3 but the increased risk of atherosclerosis is not exclusively related to traditional Framingham risk factors alone, 4 with a recent report highlighting SLE itself as an independent risk. 5 Whereas several studies have highlighted the presence of subclinical atherosclerosis in SLE, 6,7 the pathogenesis is not fully understood. It has been proposed that autoimmune vascular injury in SLE may predispose to atherosclerotic plaque formation through mechanisms that promote endothelial dysfunction, the earliest precursor for plaque development. 8 -10 Flow-mediated dilation of the brachial artery (FMD) is used clinically as an indirect bioassay for endotheliumderived nitric oxide (NO) production. The primary hemodynamic determinant of FMD is wall shear stress, 11-13 and the degree of FMD has been shown to be proportional to both systolic and diastolic shear stress (DSS) in response to incr...

Impaired microvascular properties in uncomplicated type 1 diabetes identified by Doppler ultrasound of the ocular circulation

“…[38][39][40] Techniques providing a global assessment of the circulation may not capture, or cannot localise, findings to a specific site or target organ of interest in the arterial system. 29 These results support previous findings 18,41 indicating that comprehensive spectral analysis of retrobulbar flow velocity waveforms can identify altered structure or tone in the ocular microcirculatory bed at an early preclinical stage. The technique represents a sensitive, non-invasive assessment tool with potential to track and monitor the effect of therapeutic interventions in relation to the development of complications with risk factors for cardiovascular disease.…”

“…Pathological change in the microvasculature in diabetes, including basement membrane thickening, may have little effect on altering flow resistance, 37 but may influence the pattern of wave reflection and thus structure of the flow velocity profile. 18 The ultimate shape of flow and pressure waveforms reflects the interaction between the output generated by the left ventricle and the magnitude and timing of wave reflection from impedance mismatches arising predominantly from reflection sites from microcirculatory beds.…”

“…16,17 Recent work has focused on developing comprehensive analysis techniques with the aim of extracting further discriminatory information from the flow velocity waveform profiles to identify early structural and functional abnormalities of distal microcirculatory beds. 18 Previous observations from our own and other groups have demonstrated the value of spectral analysis techniques in quantifying arterial waveform structure to identify and track change in downstream microvascular haemodynamics. 18,19 In this study we employed novel spectral analysis techniques to quantify changes in arterial waveforms from the retrobulbar and carotid circulations to investigate if subclinical microvascular abnormalities can be detected in patients with uncomplicated type 1 DM.…”

Multimodal functional and anatomic imaging identifies preclinical microvascular abnormalities in type 1 diabetes mellitus

“…In contrast, the resistive index failed to discriminate between groups. Quantifiable differences in the flow velocity waveform were most evident in waveforms recorded in the immediate proximity of the ophthalmic artery microvascular bed compared with recordings made in the more proximal carotid conduit artery, a finding we have previously reported in patients with systemic lupus erythematosus (51). Propagating waves can add destructively as well as constructively, and the effects of wave reflection in altering the Doppler flow velocity waveshape depend on the distance between recording and reflecting sites, the magnitude of wave reflection, the speed of the pulse wave, and the degree of attenuation and energy dissipation produced by blood viscosity and damping by the vessel walls (6,22,39).…”

Antiphospholipid Antibodies and Their Association with Atherosclerotic Changes in Patients with Systemic Lupus Erythematosus – Review of Literature and Own Experiences

“…Techniques designed to assess endothelial function are based on measurement of brachial artery reactivity in response to changes in blood-flow caused by passive congestion (flow-mediated vasodilatation, which is dependent on endothelial function) (Corretti et al, 2002). Studies performed in SLE patients documented an impaired endothelial function and this fact was attributed to reduced nitric oxide bioavailability resulting from increased oxidative stress in the course of SLE (El-Magadmi et al, 2004;Kiss et al, 2006;Wright et al, 2006). Furthermore, impairment of endothelial function remained significant even after adjustment for other classic atherosclerosis risk factors and the authors suggested that SLE is an independent risk factor for endothelial dysfunction (El-Magadmi et al, 2004).…”