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

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

3. 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

4. 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

5. 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.

6. 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

7. 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

8. 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)

9. 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

10. 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)

11. 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

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

14. “ 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

16. 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

17. 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)

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

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

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

21. 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

22. Va multumesc