Women with systemic lupus erythematosus (SLE) are at risk for premature atherothrombosis independent of Framingham risk factors. We investigated whether endothelial cell (EC) apoptosis predicts abnormal vasomotor tone and contributes to circulating tissue factor (TF) levels in this disease. Brachial artery flow-mediated dilation (FMD) and nitroglycerin-mediated dilation were determined in women with SLE, healthy control subjects, and subjects with coronary artery disease (CAD) (n ‫؍‬ 43/ group). Quantification of circulating apoptotic ECs was performed by flow cytometry (CD146 ؉ cells that stained for Annexin V [CD146 AnnV؉ ]) and immunofluorescent microscopy. Plasma TF was measured by enzyme-linked immunosorbent assay (ELISA). Compared with healthy control and CAD subjects, patients with SLE had higher numbers of circulating CD146 AnnV؉ cells (10 ؎ 3, 18 ؎ 5, and 89 ؎ 32 cells/mL, respectively, mean ؎ SEM; P < .01). Increased CD146 AnnV؉ cells correlated strongly with abnormal vascular function (P ‫؍‬ .037). After adjusting for known predictors of endothelial function, CD146 AnnV؉ was the only variable that predicted FMD (␤ ‫؍‬ ؊4.5, P < .001). Increased CD146 AnnV؉ was strongly associated with elevated levels of circulating TF (r ‫؍‬ .46, P ‫؍‬ .002). Circulating apoptotic ECs are elevated in young women with SLE and strongly correlate with markedly abnormal vascular function and elevated TF levels. Heightened endothelial apoptosis may represent an important mechanism for development of atherothrombosis in SLE. (Blood.

Cutaneous microvascular responses to physiological stimuli are currently being investigated as indices of vascular function and to monitor responses to therapy. We attempted to systematically assess various microvascular cutaneous flow indices in response to reactive hyperaemia in control subjects and in patients with coronary artery disease (CAD), and to correlate these with brachial artery flow-mediated dilation (FMD). Groups of 24 healthy controls and 24 subjects with CAD underwent sequential brachial FMD determination in the dominant arm, and laser Doppler imaging to assess skin blood flow in the contralateral arm in response to reactive hyperaemia induced by cuff inflation and release. Laser Doppler values were expressed as: (a) AUC(5 min) (area under the curve over 5 min of release), (b) time to peak response, (c) % reactive hyperaemia, and (d) peak perfusion ratio. As expected, FMD was attenuated in CAD patients compared with controls (1.85+/-4.29% compared with 4.30+/-4.00%; P=0.05). Percentage reactive hyperaemia (CAD, 294+/-290%; controls, 501+/-344%; P=0.04) and the time to peak response as measured by laser Doppler imaging (CAD, 16.84+/-9.61 s; controls, 9.13+/-4.43 s; P=0.001) were significantly different between the CAD and control groups, while AUC(5 min) and the peak perfusion ratio did not show significant differences. Receiver operator curves for sensitivity/specificity analysis suggested that the time to peak response derived by laser Doppler imaging was superior to FMD for the diagnosis of CAD, with an overall specificity of 91.3% (positive predictive value of 89.4%) and a sensitivity of 73.7% (negative predictive value of 77.6%). In conclusion, laser Doppler-derived indices of microvascular flow do not correlate with conduit vessel responses. However, a time to peak response of >10 s as measured by laser Doppler imaging offers superior specificity for the diagnosis of CAD compared with brachial FMD.

No abstract

Objective. To compare microvascular and macrovascular functions in a cohort of patients with primary and secondary Raynaud's phenomenon (RP) who were matched for demographic, risk factor, and severity profiles.Methods. Forty patients with primary or secondary RP matched for vascular risk factors and severity scores underwent testing of endothelial function and cold pressor responsiveness of the brachial artery. Microvascular perfusion of the digital vasculature was assessed using laser Doppler fluxmetry in response to reactive hyperemia. Plasma was assayed for endothelin 1 (ET-1), asymmetric dimethylarginine (ADMA), intercellular adhesion molecule 1, vascular cell adhesion molecule 1 (VCAM-1), and monocyte chemoattractant protein 1 (MCP-1).Results. Patients with RP had abnormal vasoconstrictor responses to cold pressor tests (CPT) that were similar in primary and secondary RP. There were no differences in median flow-mediated and nitroglycerinmediated dilation or CPT of the brachial artery in the 2 populations. Patients with secondary RP were characterized by abnormalities in microvascular responses to reactive hyperemia, with a reduction in area under the curve adjusted for baseline perfusion, but not in time to peak response or peak perfusion ratio. Plasma ET-1, ADMA, VCAM-1, and MCP-1 levels were significantly elevated in secondary RP compared with primary RP. There was a significant negative correlation between ET-1 and ADMA values and measures of microvascular perfusion but not macrovascular endothelial function.Conclusion. Secondary RP is characterized by elevations in plasma ET-1 and ADMA levels that may contribute to alterations in cutaneous microvascular function.

No abstract