Impaired responsiveness to NO in newly diagnosed patients with rheumatoid arthritis.
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.


RESULTS
Endothelial function was determined by measuring vasodilatory responses to intrabrachial artery infusions of acetylcholine (ACh at 7.5 and 15 microg/min, low and high dose, respectively), an endothelium-dependent vasodilator, and to sodium nitroprusside (SNP, 3 and 10 micro g/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.
Bergholm
Robert
R
Department of Medicine, Division of Diabetes, University of Helsinki, Helsinki, Finland.
Leirisalo-Repo
Marjatta
M
Vehkavaara
Satu
S
Mäkimattila
Sari
S
Taskinen
Marja-Riitta
MR
Yki-Järvinen
Hannele
H
D000109:Acetylcholine / Q000494:pharmacology; D000284:Administration, Oral; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001059:Apoproteins / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000378:metabolism / Q000494:pharmacology; D009599:Nitroprusside / Q000378:metabolism / Q000494:pharmacology; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D001059:Apoproteins; D008055:Lipids; D008074:Lipoproteins; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D000109:Acetylcholine; D011241:Prednisone