TY - JOUR

T1 - The role of inflammation and cardiovascular disease risk on microvascular and macrovascular endothelial function in patients with rheumatoid arthritis

T2 - a cross-sectional and longitudinal study

AU - Sandoo, Aamer

AU - Kitas, George D

AU - Carroll, Douglas

AU - Veldhuijzen van Zanten, Jet J C S

PY - 2012/5/17

Y1 - 2012/5/17

N2 - INTRODUCTION: Rheumatoid arthritis (RA) is associated with an increased risk for cardiovascular disease (CVD), and it has been postulated that RA disease-related inflammation contributes to endothelial dysfunction. The aim of the present work was to examine predictors (RA-related and CVD risk factors) and anti-tumor necrosis factor-alpha (anti-TNF-α) treatment effects on endothelial function in different vascular beds.METHODS: Microvascular endothelial function (laser Doppler imaging with iontophoresis of acetylcholine and sodium-nitroprusside), and macrovascular endothelial function (flow-mediated dilatation and glyceryl-trinitrate-mediated dilatation) were analyzed in parallel with disease activity. Individual CVD risk factors and global CVD risk were assessed cross-sectionally in 99 unselected RA patients and longitudinally (baseline, 2 weeks, and 3 months) in 23 RA patients commencing anti-TNF-α therapy.RESULTS: In this cross-sectional study, regression analyses revealed that markers of RA disease-related inflammation were not associated with microvascular or macrovascular endothelium-dependent function (P > 0.05); global CVD risk inversely correlated with microvascular endothelium-dependent function (P < 0.01) and with macrovascular endothelium-independent function (P < 0.01). In the longitudinal study, only microvascular endothelium-dependent function showed an improvement after 2 weeks of anti-TNF-α treatment when compared with baseline (437% ± 247% versus 319% ± 217%; P = 0.001), but no association was evident between change in endothelial function and change in inflammatory markers.CONCLUSIONS: Classical CVD risk may influence endothelial function more than disease-related markers of inflammation in RA. Classical CVD risk factors and anti-TNF-α medication have different effects on microvascular and macrovascular endothelial function, suggesting that combined CVD-prevention approaches may be necessary. Prospective studies examining whether assessments of vascular function are predictive of long-term CV outcomes in RA are required.

AB - INTRODUCTION: Rheumatoid arthritis (RA) is associated with an increased risk for cardiovascular disease (CVD), and it has been postulated that RA disease-related inflammation contributes to endothelial dysfunction. The aim of the present work was to examine predictors (RA-related and CVD risk factors) and anti-tumor necrosis factor-alpha (anti-TNF-α) treatment effects on endothelial function in different vascular beds.METHODS: Microvascular endothelial function (laser Doppler imaging with iontophoresis of acetylcholine and sodium-nitroprusside), and macrovascular endothelial function (flow-mediated dilatation and glyceryl-trinitrate-mediated dilatation) were analyzed in parallel with disease activity. Individual CVD risk factors and global CVD risk were assessed cross-sectionally in 99 unselected RA patients and longitudinally (baseline, 2 weeks, and 3 months) in 23 RA patients commencing anti-TNF-α therapy.RESULTS: In this cross-sectional study, regression analyses revealed that markers of RA disease-related inflammation were not associated with microvascular or macrovascular endothelium-dependent function (P > 0.05); global CVD risk inversely correlated with microvascular endothelium-dependent function (P < 0.01) and with macrovascular endothelium-independent function (P < 0.01). In the longitudinal study, only microvascular endothelium-dependent function showed an improvement after 2 weeks of anti-TNF-α treatment when compared with baseline (437% ± 247% versus 319% ± 217%; P = 0.001), but no association was evident between change in endothelial function and change in inflammatory markers.CONCLUSIONS: Classical CVD risk may influence endothelial function more than disease-related markers of inflammation in RA. Classical CVD risk factors and anti-TNF-α medication have different effects on microvascular and macrovascular endothelial function, suggesting that combined CVD-prevention approaches may be necessary. Prospective studies examining whether assessments of vascular function are predictive of long-term CV outcomes in RA are required.

KW - Adalimumab

KW - Antibodies, Monoclonal

KW - Antibodies, Monoclonal, Humanized

KW - Antirheumatic Agents

KW - Arthritis, Rheumatoid

KW - Cardiovascular Diseases

KW - Cross-Sectional Studies

KW - Endothelium, Vascular

KW - Etanercept

KW - Female

KW - Humans

KW - Immunoglobulin G

KW - Inflammation

KW - Infliximab

KW - Laser-Doppler Flowmetry

KW - Longitudinal Studies

KW - Male

KW - Middle Aged

KW - Receptors, Tumor Necrosis Factor

KW - Risk Factors

KW - Clinical Trial

KW - Journal Article

U2 - 10.1186/ar3847

DO - 10.1186/ar3847

M3 - Article

C2 - 22594788

VL - 14

SP - R117

JO - Arthritis Research & Therapy

JF - Arthritis Research & Therapy

SN - 1478-6354

IS - 3

ER -