Enhanced endothelium-dependent microvascular responses in patients with Wegener's granulomatosis.
OBJECTIVE
To assess endothelial cell (EC) function of the cutaneous microcirculation in patients with Wegener's granulomatosis (WG) and to relate EC function to EC activation and presence of atherosclerosis.


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.


CONCLUSIONS
We confirmed that WG patients 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.
Department of Internal Medicine, Division of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. h.l.a.nienhuis@int.umcg.nl
Hans L A
HL
Nienhuis
Karina
K
de Leeuw
Andries J
AJ
Smit
Johan
J
Bijzet
Coen A
CA
Stegeman
Cees G M
CG
Kallenberg
Marc
M
Bijl
D000109:Acetylcholine; D000328:Adult; D050197:Atherosclerosis / Q000150:complications*; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000473:pathology*; D016022:Case-Control Studies; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000150:complications*; D018056:Hemorheology; D006801:Humans; D007249:Inflammation / Q000150:complications*; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000473:pathology*; D014463:Ultrasonography; D014664:Vasodilation / Q000502:physiology; D014665:Vasodilator Agents
D014665:Vasodilator Agents; D009599:Nitroprusside; D000109:Acetylcholine