Universitatea de Medicina si Farmacia “Iuliu Hatieganu” Cluj-Napoca Aspecte ale afectarii cardiovasculare la pacientii cu poliartrita reumatoida Gabriel Gusetu

Rheumatoid arthritis Aggressive, potentially debilitating disease Average life expectancy shortened by 5-15 years. Early and appropriate treatment – improvement and / or control of disease

Cardiovascular involvement in RA - different presentations, some clinically obvious and others not - cardiovascular involvement plays a significant role in this diminished life expectancy in RA patients; contributing factors include: homocysteine levels, lipid profiles, sedentary lifestyle, silent coronary artery disease, vasculitis

Cardiovascular involvement in RA Pericarditis the most common manifestation of RA in the heart autopsy studies reveal up to 30% of patients with pericarditis, echocardiography studies: 50% of the patients to be affected, only 3% experience clinical symptoms be alert to rare instances of pericardial tamponade and constrictive pericarditis

Cardiovascular involvement in RA Myocarditis Nonspecific myocardial inflammation occurr in ~ 1-15 % Rheumatoid nodules of varying sizes or miocardial fibrosis may occur and can be responsible for conduction abnormalities.

Cardiovascular involvement in RA Endocarditis - Necrotizing granulomas similar to rheumatoid nodules in the aortic and mitral valves - Asymptomatic or lead to valvular dysfunction Coronary Vasculitis - rare - when present, (in the setting of systemic vasculitis), it may be asymptomatic, - rare cases of coronary vasculitis leading to myocardial infarction have been reported

Production of collagenase and other Pathophysiology of inflammation in RA Current Treatment Targets Rheumatoid Factors, anti-CCP Immune complexes B cell T cell Antigen- presenting cells B cell or macrophage Synoviocytes Pannus Articular cartilage Chondrocytes Macrophage HLA -DR Complement other cytokines IFN- & Neutrophil Mast cell TNF IL-1 Osteoclast Production of collagenase and other neutral proteases Bone Adapted from Arend WP, Dayer JM. Arthritis Rheum. 1990;33:305–15

Interleukin-1 antagonist Suppress T-Cell activation Biologic DMARD’s – Genetically Engineered Targeted Molecules Similar or Identical to Naturally Occurring Molecules TNFα antagonists: Adalimumab (Humira) Etanercept (Enbrel) Infliximab (Remicade) Interleukin-1 antagonist Anakinra (Kineret) Suppress T-Cell activation Abatacept (Orencia) Anti B-Cell monoclonal antibody Rituximab (Rituxan)

Safety Considerations with Biologic DMARD’s Serious Infections Opportunistic infections (TB) Malignancies/lymphoma Demyelination Hematologic abnormalities Administration reactions Congestive heart failure Hepatic Autoantibodies and drug induced lupus Vaccination

Biologics: Relative Contraindications Active Hepatitis B Infection Active serious infections Chronic or recurrent infections Current neoplasia History of TB or positive PPD (untreated) Congestive heart failure (Class III or IV)

cardiovascular side effects TNFα – antagonists : cardiovascular side effects TNFα – proved direct effect in pathogenesis and progression of HF FDA (2001): worsening HF NYHA III, IV class

cardiovascular side effects TNFα – antagonists : cardiovascular side effects Recent trials - non-significant progression of HF

“ The most interesting analysis in this study suggests that effective antirheumatic treatment, with traditional disease-modifying antirheumatic drugs (DMARDs), glucocorticoids, or anti-TNF biologics, reduces the risk of cardiovascular disease in rheumatoid arthritis. Some methodological issues are discussed, however, and confirmatory studies are suggested.” Arthritis Research & Therapy 2008, 10:105

Method. […. ] to investigate the influence of disease-related and treatment specific risk factors on the incidence or worsening of heart failure. Results. […….] A residual nonsignificant risk related to treatment with TNF inhibitors remained (adjusted HR 1.66 [95% confidence interval 0.67–4.1], P 0.28). This residual risk was balanced by the efficacy of the anti-TNF treatment. Conclusion. The findings of this study indicate that TNF inhibitor treatment that effectively reduces the inflammatory activity of RA is more likely to be beneficial than harmful with regard to the risk of heart failure, […] J.Listing et al. Arthritis & Rheumatism Vol. 58, No. 3, March 2008

Evaluare periodica (0, 6, 12, 18, 24, 30 luni) LOT I - Bolnavi cu PAR care primesc terapie biologica si terapie standard LOT II - Bolnavi cu PAR care nu primesc terapie biologica Evaluare periodica (0, 6, 12, 18, 24, 30 luni) Clinic Factori de risc cardiovasculari Ecocardiografic, Nt pro-BNP EKG (standard, monitorizare Holter)

A particular risk factor for women ? Is indeed RA A particular risk factor for women ?

Lori Mosca et al. Circulation. 2007;115:1481-1501

Lori Mosca et al. Circulation. 2011;123:1243-1262

LOT III Femei cu factori de risc CV LOT I Femei cu PAR LOT II Barbati cu PAR LOT III Femei cu factori de risc CV Evaluare la 2.5 ani Clinic Factori de risc cardiovascular cunoscuti Ecocardiografie EKG, Testare de stress Coronarografie, acolo unde se ridica suspiciunea de angina microvasculara

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