Impaired Responsiveness to NO in Newly Diagnosed Patients With Rheumatoid Arthritis

Abstract

Objective— Cardiovascular disease is the major cause of excessive mortality in patients with rheumatoid arthritis (RA). We determined whether endothelial dysfunction characterizes patients with newly diagnosed RA (n=10) compared with normal subjects (control group, n=33) and whether it is reversible with 6 months of anti-inflammatory therapy. Methods and Results— Endothelial function was determined by measuring vasodilatory responses to intrabrachial artery infusions of acetylcholine (ACh at 7.5 and 15 μg/min, low and high dose, respectively), an endothelium-dependent vasodilator, and to sodium nitroprusside (SNP, 3 and 10 μg/min), an endothelium-independent vasodilator. Before treatment, blood flow responses (fold increase in flow) to low-dose SNP were 30% lower in the RA versus the control group (4.1±0.4-fold versus 5.9±0.5-fold, respectively), and responses to high-dose SNP were 34% lower in the RA group versus the control group (5.1±0.6-fold versus 7.7±0.7-fold, respectively; P <0.001). The responses to low-dose ACh were 50% lower in the RA group versus the control group (3.0±0.5-fold versus 6.6±0.7-fold, respectively), and responses to high-dose ACh were 37% lower in the RA group versus the control group (5.0±0.4-fold versus 7.9±0.8-fold, respectively; P <0.001). After therapy, clinical and laboratory markers of inflammation had significantly decreased. Blood flow responses to ACh increased significantly ( P =0.02). Conclusions— We conclude that newly diagnosed patients with RA have vascular dysfunction, which is reversible with successful therapy. Therefore, early suppression of inflammatory activity may reduce long-term vascular damage.

Endothelial Dysfunction in Rheumatoid Arthritis is Improved by Anti-Tumor Necrosis Factorα Treatment

“…In our patient population a high incidence of endothelial dysfunction was found, suggesting that abnormal vasoreactivity may be a prominent feature of RA, supporting other studies (9)(10)23). However, the study protocol regarding anti-TNF<x treatment only to patients affected with uncontrolled inflammatory joint disease resistant to at least two Enr.…”

“…At the present time, in other clinical conditions such as advanced renal impairment ordyslipidaemia, endothelial dysfunction is considered a non-invasive marker of subsequent and overt cardiovascular involvement (3,6, II, I 4), and similarly it could be regarded as a biomarker of cardiovascular involvement in RA, induced by the same mechanisms of rheumatoid inflammation (6,9,30), pharmacologically modifiable and probably preceding asymptomatic or overt cardiovascular morbidity (2,(13)(14). Further studies are required in order to establish the long term significance of endothelial dysfunction and its clinical relevance for assessing cardiovascular involvement in RA patients and their complete and successful treatment (3,6,9,23).…”

Endothelial progenitor cells: Are they displaying a function in autoimmune disorders?

“…An inverse correlation between EPCs number and the Framingham risk score (Hill, 2003) in both long-standing (GonzalezJuanatey et al, 2003) and early RA patients have been documented (Bergholm et al, 2002). On the other hand have been also described increased numbers of late-outgrowth EPCs in RA, on owing an increased colony formation capacity.…”

Large artery stiffness and inflammation

“…9 Interestingly, CRP levels correlate with endothelial function in patients with coronary artery disease, 10 and induction of acute inflammation by vaccination results in endothelial dysfunction in humans, 11 which can be attenuated by co-administration of aspirin. 12 We and others have also demonstrated endothelial dysfunction in patients with acute systemic vasculitis 13,14 and chronic inflammatory conditions such as rheumatoid arthritis, 15,16 which are also associated with increased risk of cardiovascular disease. 17 Moreover, successful anti-inflammatory therapy in such patients can restore 'normal' endothelial function.…”