Impaired Responsiveness to NO in Newly Diagnosed Patients With Rheumatoid Arthritis

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Impaired Responsiveness to NO in Newly Diagnosed Patients With Rheumatoid

Arthritis

Bergholm; Marjatta Leirisalo-Repo; Satu Vehkavaara; Sari Mäkimattila;

Marja-Riitta Taskinen; Hannele Yki-Järvinen

From the Department of Medicine, Divisions of Diabetes (R.B., S.V., S.M.,

H.Y.-J.), Rheumatology (M.L.-R.), and Cardiology (M.-R.T.), University of

Helsinki, Helsinki, Finland.

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.