Effect of Medication on Microvascular Vasodilatation in Patients with Systemic Lupus Erythematosus

Abstract

The aim of this study was to investigate the microvascular responses in the skin, to local heat, iontophoretically administered acetylcholine and to sodium nitroprusside in relation to cardiovascular damage in patients with systemic lupus erythematosus (SLE) and matched controls. We also wanted to examine if the ongoing medication in SLE patients influenced this vascular response. We investigated 30 women with SLE and compared them with 20 age and sex-matched controls. The cutaneous blood flow response to local heat (+44°C), iontophoretically administered endothelium-dependent (acetylcholine), as well as independent (sodium nitroprusside) vasodilatation, was measured by laser Doppler flowmetry. Clinical data and medication were retrieved from the clinical database and patient records. The cutaneous microvascular reactivity did not differ between SLE patients and a group of matched controls nor did it correlate with cardiovascular damage [assessed by Systemic Lupus International Collaborating Clinics ⁄ American College of Rheumatology Damage Index (SLICC ⁄ ACR-DI)]. However, patients on antimalarial drugs (hydroxychloroquine n = 8 and chloroquine diphosphate n = 3) responded more strongly to sodium nitroprusside (endothelium-independent vasodilatation) compared with those without antimalarial drugs (p < 0.01). The response to acetylcholine was higher among patients on warfarin compared with those without (p < 0.05), whereas glucocorticoid use ( ‡5 mg daily) was associated with reduced response to acetylcholine (p < 0.05). Smokers in general tended to have a lower response to acetylcholine (p = 0.064). Smoking SLE patients versus non-smoking SLE patients had a significantly lower response to acetylcholine (p = 0.01). Medication with antimalarial drugs-enhanced endothelium-independent vasodilatation, while glucocorticoid use was associated with reduction and warfarin-treatment with enhancement of endothelium-dependent vasodilatation. Therefore, despite there is no difference in microvascular endothelium-dependent vasodilatation, other factors such as medication and smoking may affect vasodilatation in SLE patients.As Urowitz described the 'bimodal pattern of systemic lupus erythematosus (SLE)' some 30 years ago [1], later studies have confirmed that cardiovascular disease is greatly overrepresented in SLE patients compared with controls [2,3]. Traditional risk factors as well as SLE-specific risk factors have been thoroughly studied and both are of importance for the development of cardiovascular disease in SLE [4][5][6]. It has been suggested that antimalarial (hydroxychloroquine and chloroquine diphosphate) treatment might improve the blood lipid profile in SLE and reduce the risk of diabetes mellitus [7][8][9][10][11].There is a clinical need for non-invasive techniques to ensure the presence of and predict the development of cardiovascular disease in SLE. Non-invasive methods have been used to investigate vessel wall changes, and revealed increased vessel wall stiffness and increased pulse wave veloci...

Chronic Hydroxychloroquine Improves Endothelial Dysfunction and Protects Kidney in a Mouse Model of Systemic Lupus Erythematosus

“…[47][48][49] However, the cutaneous microvascular reactivity to local heat or iontophoretically administered acetylcholine did not differ between patients with SLE and matched controls. 50 However, in NZBWF1 mice, which have uniform genetics and environmental conditions, we found impaired aortic endothelium-dependent relaxation response to acetylcholine. Interestingly, Ryan and McLemore 51 found that the impaired response to acetylcholine begins before the development of proteinuria and increased blood pressure, suggesting that early changes in vessel function may contribute to the development of hypertension during SLE.…”

Hydroxychloroquine: From Malaria to Autoimmunity

“…However, a different study in Chinese SLE patients did not show significant effect on serum lipid profile, but these patients had mild or absent disease-activity and used low corticosteroid dose [53]. Of note, in addition to its metabolic effects on blood sugar and lipids, HCQ was recently also shown to improve endothelial function and to protect against thrombovascular events in lupus patients [54][55][56].…”

Hydroxychloroquine in lupus: emerging evidence supporting multiple beneficial effects

“…Antimalarials have been found to increase endothelium‐dependent vasodilatation 37 . One study has shown a significantly lower prevalence of vascular stiffness in premenopausal women with SLE treated with hydroxychloroquine 38 .…”