Rheumatoide Arthritis, Inflammation und Atherosklerose

Abstract

Patients with rheumatoid arthritis (RA) have a two to five times increased risk of developing premature cardiovascular disease that shortens life expectancy by 5-10 years. Traditional risk factors known to promote and accelerate the progression of atherosclerotic lesions however, are often absent in patients with RA. Many similarities have emerged between the paradigm of inflammation in the pathogenesis of atherosclerosis and the well-established mechanisms of inflammation in the pathogenesis of RA. Hence it is intriguing to speculate that inflammation in RA is not confined to the joints but also present in the vessel wall. Indeed, low-grade inflammation and endothelial dysfunction play pivotal roles in the initiation, progression and propagation of the atherosclerotic process. While the healthy endothelium prevents adhesion of mononuclear cells, the defence mechanisms cease under the influence of cardiovascular risk factors and inflammation and they express adhesion molecules (selectins, vascular adhesion molecule-([VCAM-]1, intercellular adhesion molecule-[ICAM-]1) that promote the adherence of monocytes. This expression is induced by pro-inflammatory cytokines such as interleukin-(IL-)1beta and tumor necrosis factor-(TNF-)alpha, by C-reactive protein (CRP), and CD40/CD40 ligand interactions. As all of these factors are present at increased levels in the systemic circulation in RA, it appears possible that they might impact the endothelium as well. Further similarities include proteolytic enzymes such as matrix metalloproteinases (MMPs) that play a role in joint destruction as well as in destabilization and rupture of vulnerable atherosclerotic plaques. In addition, coagulation factors such as increased levels of tissue factor (TF), van Willebrand factor (vWF) and plasminogen activator inhibitor-(PAI-)1 are important in both, RA and CAD. Endothelial dysfunction has shown to correlate with cardiovascular prognosis in several studies, which indicates its clinical relevance. Endothelial function measurement is performed in the coronary or peripheral circulation (by venous occlusion plethysmography or flow-mediated dilation). Recent studies have demonstrated impaired endothelial function in patients with RA, already at early stages of the disease. Similar results are found in patients with systemic lupus erythematosus (SLE), indicating that inflammation per se may impair altering vascular function. This and more evidence supports the notion that inflammation plays a pivotal role in vascular dysfunction and may by these mechanisms explain at least part of the excess morbidity and mortality observed in RA and SLE. In light of the growing evidence of increased cardiovascular morbidity and mortality mostly independent of traditional risk factors, treatment strategies in RA should not only aim at relieving symptoms and inhibiting joint destruction but should have a beneficial effect on the vasculature to reduce cardiovascular events. Indeed, an improvement in endothelial function in RA was recently demonstrated by anti-...

Komorbiditeti kod oboljelih od reumatoidnog artritisa

“…Rezultati su pokazali da je jedini važan faktor rizika za peptički ulkus kod bolesnika koji su uzimali NSAIL bila infekcija sa Helicobacter pylori (stepen vjerovatnoće 3,10; 95% CI 1,30-7,30), dok dispepsija, muški pol, godine starosti i anemija, prema rezultatima ovog istraživanja, nisu bili značajni faktori rizika. Zaključeno je da upotreba NSAIL povećava rizik od peptičkog ulkusa 3-5 puta u bolesnika sa Helicobacter pylori pozitivnim, ali i sa Helicobacter pylori negativnim testom [22][23][24][25][26].…”

“…Ovo je potvrdilo druga saznanja da dugoročna terapija kortikosteroidima može biti glavni doprinoseći faktor u razvoju infekcija donjih respiratornih puteva. Jedna od studija je pokazala da su incidenca infekcije donjih respiratornih puteva i smrtnost povezana sa njima udvostručene kod RA, i predložila niz mjera za njihovo smanjenje [24]. Među njima su bili imunizacija svih pacijenata protiv pneumokoka i gripa, izbjegavanje dugoročnih oralnih kortikosteroida i privremenog prekida DMARD tokom bilo koje interkurentne infekcije koja zahtijeva antibiotike.…”

“…Ovi nalazi su bili nezavisni od starosti, pola i statusa pušenja. Potrošnja oralnih kortikosteroida se smanjila za 50%, dok je stopa imunizacije oboljelih od RA protiv gripa poboljšana za 86%, a protiv pneumokoka do 65% [24][25][26][27][28][29][30].…”

Artrite reumatóide e doença cardiovascular na atualidade: o que sabemos sobre essa associação e o que podemos fazer pelo paciente?

“…É o caso das metaloproteinases da matriz, enzimas proteolíticas que não só participam da destruição articular como também atuam na desestabilização e rotura de placas ateroscleróticas vulneráveis. De forma similar, níveis aumentados de fatores de coagulação e citocinas inflamatórias como fibrinogênio, fator tecidual, fator de von Willebrand, inibidor de ativação do plasminogênio, proteína-C reativa (PCR), interferon-gama, fator de necrose tumoral-α (TNF-α), interleucina-6 (IL-6) e interleucina-I beta são encontrados tanto na AR quanto na doença coronariana 5,[11][12][13] . Além disso, outra molécula que encontra-se em níveis elevados em pacientes com AR é o óxido nítrico, produzido por células endoteliais e responsável em parte por mecanismos de apoptose e regulação de linfócitos T em placas ateroscleróticas 12 .…”

“…Nos últimos anos, diferentes estudos têm demonstrado que pacientes com AR apresentam de 5 a 10 anos a menos de expectativa de vida em relação à população em geral. Essa diminuição está relacionada ao maior risco de doenças cardiovasculares, que é de 2 a 5 vezes maior que na população em geral 2,3,5,6 . Dessa forma, o risco cardiovascular absoluto em portadores de AR é equivalente ao dos indivíduos sem AR que são 5 a 10 anos mais velhos [6][7][8] .…”