Transcript Science Fair Project

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
Pathophysiology of inflammation in RA
Current Treatment
Targets
Rheumatoid
Factors,
anti-CCP
B cell
Immune complexes
Complement
T cell
IFN- &
Neutrophil
Antigenpresenting
cells
B cell or
macrophage
Pannus
other
cytokines
Synoviocytes
Macrophage
Mast cell
TNF
Chondrocytes
IL-1
Osteoclast
Articular
cartilage
Production of collagenase and other
neutral proteases
Bone
Adapted from Arend WP, Dayer JM. Arthritis Rheum. 1990;33:305–15
Biologic DMARD’s –
Genetically Engineered Targeted Molecules
Similar or Identical to Naturally Occurring Molecules

TNFα antagonists:




Interleukin-1 antagonist


Anakinra (Kineret)
Suppress T-Cell activation


Adalimumab (Humira)
Etanercept (Enbrel)
Infliximab (Remicade)
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)
TNFα – antagonists :
cardiovascular side effects
TNFα – proved direct effect in pathogenesis and
progression of HF
FDA (2001): worsening HF NYHA III, IV class
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 diseasemodifying 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

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)
Is indeed RA
A particular risk factor for women ?
Lori Mosca et al. Circulation. 2007;115:1481-15
Lori Mosca et al. Circulation. 2011;123:1243-12

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
Va multumesc