C-reactive protein: the underlying cause of microvascular dysfunction in rheumatoid arthritis.
OBJECTIVE
RA is a chronic autoimmune inflammatory condition associated with increased cardiovascular morbidity and mortality. Endothelial dysfunction, a marker of early atherosclerotic disease, occurs in some inflammatory diseases but this relationship has not been previously explored within the microvasculature of patients with RA. We therefore assessed forearm microvascular endothelial function in patients with RA and determined its relationship to RA disease activity and inflammation.


METHODS
A total of 128 RA patients with no previous history of cardiovascular disease were evaluated. Endothelium-dependent and -independent forearm skin microvascular function was measured using laser Doppler imaging after iontophoretic delivery of acetylcholine (ACh) and sodium nitroprusside (SNP), respectively. Parameters of RA disease activity and inflammation were also checked.


RESULTS
There was a significant negative correlation between the level of inflammation measured by log(10)CRP and maximum vasodilatation measured by peak ACh response (r(2) = -0.209, P = 0.018, Pearson correlation test). In a multiple regression model, age (beta = -0.449, P < 0.0001) and log(10)CRP (beta = -0.193, P = 0.026) were independently negatively associated with ACh responses. When RA patients were sub-divided according to their systemic inflammatory status (CRP > 10 mg/l vs CRP </= 10 mg/l), the high CRP group showed lower vasodilator responses to ACh [P = 0.018, analysis of variance (ANOVA)] and SNP (P = 0.05, ANOVA) than the low CRP group.


CONCLUSIONS
In this large cross-sectional study, we found for the first time systemic inflammation (CRP) to be independently associated with microvascular dysfunction in patients with RA. This strong correlation was independent of other conventional vascular risk factors.
Institute of Cardiovascular Research, Vascular and Inflammatory Diseases Research Unit, University Division of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. Lauberdoc@hotmail.com
B
B
Galarraga
F
F
Khan
P
P
Kumar
T
T
Pullar
J J F
JJ
Belch
D000109:Acetylcholine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000503:physiopathology*; D002097:C-Reactive Protein / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009599:Nitroprusside; D012720:Severity of Illness Index; D014665:Vasodilator Agents
D014665:Vasodilator Agents; D009599:Nitroprusside; D002097:C-Reactive Protein; D000109:Acetylcholine