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Enhanced Endothelium-Dependent Microvascular Responses in Patients with Wegener's Granulomatosis HANS L.A. NIENHUIS, KARINA de LEEUW, ANDRIES J. SMIT, JOHAN BIJZET, COEN A. STEGEMAN, CEES G.M. KALLENBERG, and MARC BIJL
ABSTRACT. Methods. We studied 28 WG patients with inactive disease and 28 age and sex matched controls. Common carotid intima-media thickness (IMT), as a measure of atherosclerosis, was determined by ultrasonography. EC function of microcirculation in the fingers was assessed using laser Doppler fluxmetry in combination with iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP), which are endothelium-dependent and endothelium-independent vasodilators, respectively. In addition to vascular responses, traditional cardiovascular risk factors were recorded, and EC activation was assessed by serological measures. Results. WG patients had increased IMT compared to controls (0.71 mm vs 0.66 mm; p < 0.05). In WG patients IMT correlated positively with age and body mass index (BMI), and negatively with duration of prednisolone use and cumulative prednisolone dose. Levels of von Willebrand factor and C-reactive protein were increased in patients with WG (p < 0.05). ACh-induced but not SNP-induced vasodilatation was enhanced in WG patients compared to controls. When patients and controls with increased IMT were excluded, the difference in relative response to ACh became significant (median 567% vs 334%; p = 0.007). The response to ACh correlated negatively with age. Conclusion. We confirmed that patients with WG have accelerated atherosclerosis as measured by IMT. EC activation and disturbed microvascular endothelium-dependent vasodilatation were present in the microcirculation of WG patients with inactive disease and without signs of atherosclerosis, indicating and contributing to a proatherogenic state. (First Release July 15 2007; J Rheumatol 2007;34:1875-81) Key Indexing Terms:
ENDOTHELIAL FUNCTION
From the Department of Internal Medicine, Division of Rheumatology and Clinical Immunology, Division of Vascular Diseases, and Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. H.L.A. Nienhuis, BSc; K. de Leeuw, MD; J. Bijzet, BSc; C.G.M. Kallenberg, MD, PhD; M. Bijl MD, PhD, Division of Rheumatology and Clinical Immunology; A.J. Smit, MD, PhD, Division of Vascular Diseases; C.A. Stegeman, MD, PhD, Division of Nephrology, University Medical Center Groningen. Address reprint requests to Dr. H. Nienhuis, Department of Internal Medicine, Division of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, PO Box 30.001, 9700 RB Groningen, The Netherlands. E-mail: h.l.a.nienhuis@int.umcg.nl Accepted for publication May 21, 2007. |
