RT Journal Article
SR Electronic
T1 Endothelial dysfunction and atherosclerosis in rheumatoid arthritis: a multiparametric analysis using imaging techniques and laboratory markers of inflammation and autoimmunity.
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 398
OP 406
VO 35
IS 3
A1 György Kerekes
A1 Zoltán Szekanecz
A1 Henriett Dér
A1 Zsuzsa Sándor
A1 Gabriella Lakos
A1 László Muszbek
A1 István Csipö
A1 Sándor Sipka
A1 Ildikó Seres
A1 György Paragh
A1 János Kappelmayer
A1 Edit Szomják
A1 Katalin Veres
A1 Gyula Szegedi
A1 Yehuda Shoenfeld
A1 Pál Soltész
YR 2008
UL http://www.jrheum.org/content/35/3/398.abstract
AB OBJECTIVE: Cardiovascular disease is a leading cause of mortality in rheumatoid arthritis (RA). Endothelial dysfunction often precedes manifest atherosclerosis. We assessed endothelial dysfunction and atherosclerosis in RA in context with laboratory markers. METHODS: Fifty-two patients with RA and 40 matched healthy controls were studied. We assessed common carotid intima-media thickness (ccIMT) and flow- (FMD) and nitroglycerine-mediated vasodilation (NMD). We also assayed numerous immunological and metabolic laboratory markers. RESULTS: FMD was significantly lower in RA (5.32% +/- 4.66%) compared to controls (8.30% +/- 3.96%) (p = 0.001). NMD was preserved in RA. ccIMT was significantly greater in patients with RA (0.63 +/- 0.14 mm) versus controls (0.54 +/- 0.15 mm) (p = 0.012). In patients with RA, ccIMT correlated with FMD% (R = -0.318, p = 0.022), age (R = 0.831, p < 0.001), and anti-dsDNA levels (R = 0.463, p = 0.006). FMD% correlated with serum interferon-gamma (IFN-gamma) levels (R = 0.516, p = 0.014). NMD% correlated inversely with the percentage of Th0 lymphocytes (R = -0.636, p = 0.006), serum immune complex (R = -0.692, p < 0.001), and IgM levels (R = -0.606, p = 0.003). Patients with RA were divided as "low" (< 0.65 mm) versus "high" (> 0.65 mm) ccIMT groups, and into "normal" (> 5%) versus "impaired" (< 5%) FMD% subsets. Low and high ccIMT groups differed significantly in age and serum interleukin 1 (IL-1) and anti-dsDNA levels. RA patients with normal versus impaired FMD% differed significantly in age, disease duration, and serum IFN-gamma levels. Lipoprotein(a) [Lp(a)] also correlated with rheumatoid factor (RF) and C-reactive protein (CRP); homocysteine (HCy) correlated with CRP and correlated inversely with folate and vitamin B12 production. Paraoxonase-1 (PON-1) activity correlated with serum tumor necrosis factor-alpha(TNF-alpha) and IL-6 levels. CONCLUSION: This was a well characterized RA population, where FMD and ccIMT were impaired, indicating early endothelial dysfunction and accelerated atherosclerosis, respectively. RA-related autoimmune-inflammatory mechanisms and metabolic factors including anti-CCP, RF, CRP, circulating immune complexes, IgM, TNF-alpha, IL-6, Th0/Th1 ratio, HCy, folate, vitamin B12, and PON-1 may all be involved in the development of vascular disease in RA. Although ccIMT and FMD, as well as some laboratory factors, have been assessed by other investigators in RA-associated atherosclerosis, our results regarding the possible involvement of anti-CCP, anti-dsDNA, Lp(a), some cytokines, and PON-1 activity are novel. Early determination of FMD% and ccIMT may be useful to assess RA patients with high cardiovascular risk.