aspecte ale afectarii cardiovasculare la pacientii cu poliartrita reumatoida gabriel gusetu...

Aspecte ale afectarii cardiovasculare la pacientii cu poliartrita reumatoida

Gabriel Gusetu

Universitatea de Medicina si Farmacia “Iuliu Hatieganu” Cluj-Napoca

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

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

Cardiovascular involvement in RA

B cell

T cell

Antigen-presenting

cells

B cell ormacrophage Synoviocytes

Pannus

Articularcartilage

Chondrocytes

Macrophage

HLA -DRother cytokines

IFN- &

Production of collagenase and otherneutral proteases

Osteoclast

TNFIL-1

RheumatoidFactors, anti-CCP

Immune complexes

Bone

Complement

Neutrophil

Mast cell

Adapted from Arend WP, Dayer JM. Arthritis Rheum. 1990;33:305–15

Current Treatment Targets

Pathophysiology of inflammation in RA

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)

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

TNFα – antagonists : cardiovascular side effects

“ 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)

Clinic

Factori de risc cardiovasculari

Ecocardiografic, Nt pro-BNP

EKG (standard, monitorizare Holter)

LOT I - Bolnavi cu PAR care primesc terapie

biologica si terapie standard

LOT II - Bolnavi cu PAR care nu primesc terapie

biologica

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 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

Va multumesc