Atherosclerosis in early rheumatoid arthritis: very early endothelial activation and rapid progression of intima media thickness.
BACKGROUND
In this study we aimed to investigate whether there are indications of premature atherosclerosis, as measured by endothelial dependent flow-mediated dilation (ED-FMD) and intima media thickness (IMT), in patients with very early RA, and to analyze its relation to biomarkers of endothelial dysfunction, taking inflammation and traditional cardiovascular disease (CVD) risk factors into account.


METHODS
Patients from the three northern counties of Sweden diagnosed with early RA are followed in an ongoing prospective study of CVD co-morbidity. Of these, all patients aged ≤60 years were consecutively included in this survey of CVD risk factors (n = 79). Forty-four age and sex matched controls were included. IMT of common carotid artery and ED-FMD of brachial artery were measured using ultrasonography. Blood was drawn for analysis of lipids, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA)-mass, VonWillebrand factor (VWF), soluble intercellular adhesion molecule-1 (sICAM), soluble vascular cell adhesion molecule-1 (sVCAM), sE-selectin, sL-selectin and monocyte chemotactic protein-1 (MCP-1). In a subgroup of 27 RA patients and their controls the ultrasound measurements were reanalysed after 18 months.


RESULTS
There were no significant differences between RA patients and controls in terms of IMT or ED-FMD at the first evaluation. However after 18 months there was a significant increase in the IMT among the patients with RA (P < 0.05). Patients with RA had higher levels of VWF, sICAM-1 (P < 0.05) and of MCP-1 (P = 0.001) compared with controls. In RA, IMT was related to some of the traditional CVD risk factors, tPA-mass, VWF (P < 0.01) and MCP-1 and inversely to sL-selectin (P < 0.05). In RA, ED-FMD related to sL-selectin (P < 0.01). DAS28 at baseline was related to PAI-1, tPA-mass and inversely to sVCAM-1 (P < 0.05) and sL-selectin (P = 0.001).


CONCLUSIONS
We found no signs of atherosclerosis in patients with newly diagnosed RA compared with controls. However, in patients with early RA, IMT and ED-FMD were, to a greater extent than in controls, related to biomarkers known to be associated with endothelial dysfunction and atherosclerosis. After 18 months, IMT had increased significantly in RA patients but not in controls.
Södergren
Anna
A
Department of Public Health and Clinical Medicine/Rheumatology, University Hospital, 901 85 Umeå, Sweden. anna.sodergren@medicin.umu.se
Karp
Kjell
K
Boman
Kurt
K
Eriksson
Catharina
C
Lundström
Elisabet
E
Smedby
Torgny
T
Söderlund
Lisbet
L
Rantapää-Dahlqvist
Solbritt
S
Wållberg-Jonsson
Solveig
S
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000453:epidemiology* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002339:Carotid Arteries / Q000000981:diagnostic imaging*; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging* / Q000453:epidemiology* / Q000378:metabolism; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology; D017539:Tunica Intima / Q000000981:diagnostic imaging*; D014463:Ultrasonography; D014664:Vasodilation / Q000502:physiology; D055815:Young Adult
D015415:Biomarkers