Rheumatoid Arthritis: Kerekes G

Szekanecz Z, Kerekes G, Dér H, Sándor Z, Szabó Z, Végvári A, Simkovics E, Soós L, Szentpétery A, Besenyei T, Szücs G, Szántó S, Tamási L, Szegedi G, Shoenfeld Y, Soltész P. · Division of Rheumatology, Third Department of Medicine, University of Debrecen Medical and Health Science Center, Debrecen, Hungary. · Ann N Y Acad Sci. · Pubmed #17893998 No free full text.

Abstract: Cardiovascular disease is a leading cause of mortality in rheumatoid arthritis (RA). Endothelial dysfunction often precedes manifest atherosclerosis. Both traditional, Framingham risk factors and inflammation-associated factors are involved in RA-associated atherosclerosis. Among imaging techniques, the early determination of common carotid intima-media thickness (ccIMT), flow-mediated vasodilation (FMD), and nitroglycerine-mediated vasodilation (NMD) may be useful to determine atherosclerosis and endothelial dysfunction. We and others found increased ccIMT and impaired FMD in RA patients. Among immunological and metabolic laboratory markers, anticyclic citrullinated peptide (anti-CCP) antibodies, IgM rheumatoid factor, circulating immune complexes, pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), Th0/Th1 T cells, homocysteine, dyslipidemia, decreased folate and vitamin B12 production, and impaired paraoxonase activity may all be involved in the development of vascular disease in RA. The early diagnosis of endothelial dysfunction and atherosclerosis, active immunosuppressive treatment, the use of drugs that control atherosclerosis, changes in sedentary lifestyle, and the close follow-up of RA patients may help to minimize cardiovascular risk in these individuals.

Kerekes G, Soltész P, Dér H, Veres K, Szabó Z, Végvári A, Szegedi G, Shoenfeld Y, Szekanecz Z. · Cardiovascular Unit, Third Department of Medicine, University of Debrecen Medical and Health Science Center, Móricz Zs krt. 22., 4032, Debrecen, Hungary. · Clin Rheumatol. · Pubmed #19319624 No free full text.

Abstract: Increased cardiovascular mortality has been associated with rheumatoid arthritis (RA). There have been reports indicating that tumor necrosis factor blockers may exert favorable but transient effects on lipid profile, flow-mediated vasodilation (FMD) of the brachial artery, and common carotid intima-media thickness (ccIMT) in RA. In this study, we assessed the effects of rituximab on FMD, ccIMT, and lipid profile. Five female RA patients received two infusions of 1000 mg rituximab i.v. High-resolution B-mode ultrasound was used to assess brachial FMD and ccIMT. We also determined plasma total cholesterol (TC), HDL-C, LDL-C, and triglyceride (Tg) levels. Assessments were performed at baseline, as well as at weeks 2, 6, and 16 after the first infusion. Rituximab (RTX) treatment resulted in a rapid and sustained improvement in FMD. The mean improvement was 30%, 22%, and 81% at weeks 2, 6, and 16, respectively. RTX had little effect on atherosclerosis within this short period of time; however, we observed 10%, 9%, and 2% decreases in ccIMT at weeks 2, 6, and 16, respectively. RTX therapy resulted in 3-11% decrease in TC, as well as 14-35% increase in HDL-C levels. Two infusions of RTX exerted early and sustained favorable effects on endothelial dysfunction, as well as plasma TC and HDL-C levels. RTX may also decrease ccIMT; however, longer follow-up is needed to assess the prolonged effects of RTX on vascular function and lipid profile in RA patients.

Soltész P, Dér H, Kerekes G, Szodoray P, Szücs G, Dankó K, Shoenfeld Y, Szegedi G, Szekanecz Z. · Cardiovascular Unit, Institute of Medicine, Third Department of Medicine, University of Debrecen Medical and Health Science Center, Debrecen, 4032, Hungary. · Clin Rheumatol. · Pubmed #19224126 No free full text.

Abstract: Patients with autoimmune diseases may have increased vascular risk leading to higher mortality rates. Novel imaging techniques are necessary for the early assessment and management of these patients. In this study, we compared augmentation index (AIx) and pulse wave velocity (PWV), indicators of arterial stiffness, to brachial arterial flow-mediated vasodilation (FMD) and common carotid artery intima-media thickness (ccIMT), standard indicators of endothelial dysfunction and atherosclerosis, respectively. We wished to assess the vascular status of autoimmune patients by using a novel, cheap, and reproducible technique, the arteriograph. Altogether, 101 patients with systemic autoimmune diseases including primary antiphospholipid syndrome, systemic sclerosis, rheumatoid arthritis, and polymyositis, all having various types of vasculopathies, as well as 36 healthy individuals were investigated. Arterial stiffness was assessed by a TensioClinic arteriograph, a recently validated technique. Brachial arterial FMD and ccIMT were determined using high-resolution ultrasonography. Autoimmune patients exerted impaired FMD (3.7 +/- 3.8%), increased ccIMT (0.7 +/- 0.2 mm), AIx (1.2 +/- 32.2%), and PWV (9.7 +/- 2.4 m/s) in comparison to control subjects (FMD = 8.4 +/- 4.0%; ccIMT = 0.6 +/- 0.1 mm; Aix = -41.1 +/- 22.5%; PWV = 8.0 +/- 1.5 m/s; p < 0.05). We found a significant negative correlation of FMD with AIx (R = -0.64; p < 0.0001) and PWV (R = -0.37; p = 0.00014). There were significant positive correlations between ccIMT and AIx (R = 0.34; p = 0.0009), ccIMT and PWV (R = 0.44; p < 0.0001), as well as AIx and PWV (R = 0.47; p < 0.0001). AIx, PWV, and ccIMT positively correlated and FMD negatively correlated with the age of the autoimmune patients. Arterial stiffness indicated by increased AIx and PWV may be strongly associated with endothelial dysfunction and overt atherosclerosis in patients with autoimmune diseases. Assessment of arterial stiffness, FMD, and ccIMT are reproducible and reliable noninvasive techniques for the complex assessment of vascular abnormalities in patients at high risk.

Kerekes G, Szekanecz Z, Dér H, Sándor Z, Lakos G, Muszbek L, Csipö I, Sipka S, Seres I, Paragh G, Kappelmayer J, Szomják E, Veres K, Szegedi G, Shoenfeld Y, Soltész P. · Cardiovascular Unit, Division of Rheumatology, and Laboratory of Immunology, Third Department of Medicine, Hungary. · J Rheumatol. · Pubmed #18203326 No free full text.

Abstract: 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.

Kerekes G, Bodolay E, Sipka S, Szomják E, Veres K, Zeher M, Szegedi G, Soltész P. · Orvos-és Egészségtudományi Centrum, Altalános Orvostudományi Kar, III. Belgyógyászati Klinika, Intenzív Osztály. · Orv Hetil. · Pubmed #17918635 No free full text.

Abstract: INTRODUCTION: The most common systemic autoimmune diseases, as the rheumatoid arthritis (RA) and the systemic lupus erythematosus (SLE) are associated with accelerated atherosclerosis and increased cardiovascular morbidity and mortality. The authors' aim was to determine the endothelial dysfunction and the accelerated atherosclerosis in patients with undifferentiated connective tissue disease (UCTD), in a preliminary phase of defined connective tissue diseases. PATIENTS AND METHODS: Twenty-two UCTD patients and twenty age and sex-matched controls were included. Using high-resolution B-mode ultrasound, the authors' measured the intima-media thickness (IMT) of the common carotid artery (CCA), and the diameter of brachial artery at rest, during reactive hyperemia, and after sublingual glyceryl trinitrate administration. The clinical, the demographical status and the serological profile of UCTD patients were also assessed. RESULTS: There was no significant difference between the groups considered to the traditional risk factors. The endothelium dependent vasodilatation was significantly impaired in UCTD patients as compared to the controls (5.3 +/- 3.03% vs. 8.85 +/- 4.02%, P < 0.002). The authors' have not found significant difference between the two groups either at the endothelium independent vasodilatation or at the CCA-IMT. CCA-IMT correlated significantly with the age (R = 0.819, p < 0.001) and with the anti-DNA antibody levels (R = 0.563, P < 0.008). CONCLUSIONS: The endothelium-dependent vasodilatation of patients with UCTD is reduced before development of a defined connective tissue disease and the potential anti-atherogenic treatment. The endothelium dependent vasodilatation is a more sensitive method to determine an early atherosclerotic process. The authors' found moderate correlation between the CCA-IMT and the anti-DNA antibody levels.