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...

Quantitative analysis of the arterial pressure pulse waveform recorded by applanation tonometry of the radial artery can track NO (nitric oxide)-mediated modulation of arterial smooth muscle tone. The changes in pressure pulse waveform morphology result from pulse wave reflection arising predominantly from smaller arteries and arterioles. Employing Doppler ultrasound to record the spectral flow velocity waveform in the ophthalmic artery, we studied the effects of NO modulation on waveforms recorded in the proximity of the terminal ocular microcirculatory bed. In healthy young men (n=10; age 18-26 years), recordings were made at baseline, following 300 mug of sublingual GTN (glyceryl trinitrate) and during the intravenous infusion of 0.25 and 0.5 mg/kg of L-NAME (N(G)-nitro-L-arginine methyl ester). Peaks (P1, P2 and P3) and nodes (N1, N2 and N3) on the arterial flow velocity waveform were identified during the cardiac cycle and employed to quantify wave shape change in response to the haemodynamic actions of the pharmacological interventions. The administration of GTN resulted in a significant (P<0.05) increase in heart rate without significant alteration in blood pressure. At the doses employed, L-NAME did not significantly alter systemic haemodynamics. With the exception of peak Doppler systolic velocity, all other peaks and nodes decreased significantly in response to GTN (P<0.05 for all points compared with baseline). In response to the administration of L-NAME, all peaks and nodes decreased significantly (P<0.05 for all points compared with baseline). The resistive index, a ratio calculated from the peak and trough flow velocities employed to assess change in flow resistance, increased significantly in response to GTN (0.77 at baseline compared with 0.85; P<0.05). Quantification of changes in the flow velocity spectral waveform during the cardiac cycle sensitively identified NO modulation of smooth muscle tone prior to alteration in systemic haemodynamics. Focusing on the resistive index, which identifies isolated points on the waveform describing the excursions of flow, may provide misleading information in relation to the haemodynamic effects of drug interventions.

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Structural and functional changes in wall and endothelial components of arterial blood vessels underlie the accelerated vascular disease progression in systemic lupus erythematosus (SLE). Using pulse contour analysis we sought to determine if subclinical vascular abnormalities could be identified in a well-characterised cohort of patients with SLE who had no increase in traditional cardiovascular risk factors. Radial artery pressure waveforms were obtained by applanation tonometry and pressure envelopes were analysed by descriptive and model-based approaches. Waveshape morphology was quantified by a novel eigenvector approach and model-based compliance indices of the large arteries (C1, capacitative arterial compliance) and small arteries (C2, reflective arterial compliance) were derived using a third-order four-element modified Windkessel model. Data were recorded from 30 patients with SLE (mean age 44 +/- 7 years and mean SLAM-R 10 +/- 4) and 19 age-matched control subjects. Significant differences in the lower frequency sinusoidal components of the pressure waveforms were evident between groups (P < 0.05). Both C1 and C2 were significantly reduced in patients with SLE: C1 mean +/- SD 13.5 +/- 4.0 ml/mmHg x 10 versus C1 17.5 +/- 4.8 ml/mmHg x 10 (P = 0.003 in patients vs. controls, respectively) and C2 5.2 +/- 3.4 ml/mmHg x 100 versus C2 9.4 +/- 2.8 ml/mmHg x 100 (P < 0.001 in patients vs. controls, respectively). In this group of SLE patients, without an excess of traditional cardiovascular risk factors and SLAM-R scores indicating mild disease, descriptive and model-based analysis of arterial waveforms identified vascular abnormalities at a preclinical stage.

M icrovascular changes occur early in diabetes mellitus. Doppler ultrasound enables non-invasive identification of ocular microvascular haemodynamics through interrogation of blood flow velocity waveforms. Wave decomposition permits the spectrum of sinusoidal components comprising flow velocity waveforms to be quantified. We hypothesised that comprehensive interrogation of waveforms would be more sensitive in identifying microvascular abnormalities than traditional analysis employing the resistive index.Thirty-four subjects with type 2 diabetes and 20 healthy controls between 30 and 70 years old were recruited. Doppler flow velocity waveform signals were captured from the ophthalmic and carotid arteries under standardised conditions. The signals were analysed using a wave decomposition algorithm and the sinusoidal components of average waveforms were compared between groups at both arterial sites.The diabetes group displayed significant differences in the lower frequency sinusoidal components of both the ophthalmic artery (p<0.001) and, to a lesser extent, the carotid artery (p<0.05) waveforms compared with controls, with no difference noted in the resistive index at either site.We conclude that wave decomposition analysis of Doppler flow velocity waveforms, recorded in proximity of the terminal vascular bed of interest, can identify subtle microvascular haemodynamic abnormalities not detected by traditional methods of analysis. Br J Diabetes Vasc Dis 2011;11:243-248