THE CARDIOVASCULAR INFLAMMATORY CONTINUUM DR AB MAHARAJ

Transcription

1 THE CARDIOVASCULAR INFLAMMATORY CONTINUUM DR AB MAHARAJ

2 Disclosures: On National Advisory Boards of: (1) Pfizer Pharmaceuticals (2) MSD (3) Roche Pharmaceuticals (4) Abbott International: AfME Rheumatology Board of Pfizer Educational Grant : Servier Laboratories

3 Hansson GK. N Engl J Med 2005;352:

4 Hansson GK. N Engl J Med 2005;352:

5 Hansson GK. N Engl J Med 2005;352:

6 Hansson GK. N Engl J Med 2005;352:

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8 Atherosclerosis in Inflammatory disorders Skaggs, B. J. et al. (2012) Accelerated atherosclerosis in patients with SLE mechanisms and management Nat. Rev. Rheumatol. doi: /nrrheum

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10 Figure 1. In RA, primary site of inflammation is synovial tissue, from which cytokines can be released into systemic circulation.

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12 Table 1 Associations between chronic inflammatory diseases and vascular damage Kaplan MJ (2009) Management of cardiovascular disease risk in chronic inflammatory disorders Nat Rev Rheumatol doi: /nrrheum

13 Rheumatoid Arthritis Prevalence: 1 % Increased mortality from CVD MI 2x commoner in with RA as compared to controls Traditional risk factors do not influence CVS mortality in RA pts. RA pts have a higher prevalence of diastolic dysfunction Increased mortality in RA pts with MI as compared to controls

14 High incidence of silent ischaemia RA specific factors play a role Extent of atherosclerosis proportional to disease activity Male and advanced age of onset poor prognosis

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19 SLE Autoimmune disease affecting predominantly women of child-bearing age High rate of premature CVD CVD most common cause of death in pts with SLE Framingham risk factors are less important predictors of CVS events in pts with active SLE > 40% of pts with SLE have asymptomatic myocardial perfusion abnormalities High incidence of increased LV mass

20 Risk Factors for Atherosclerosis and Risk Factors Related to Systemic Lupus Erythematosus (SLE). Hahn BH. N Engl J Med 2003;349:

21 Figure 2 Continuum of SLE-specific and traditional risk factors for CVD Skaggs, B. J. et al. (2012) Accelerated atherosclerosis in patients with SLE mechanisms and management Nat. Rev. Rheumatol. doi: /nrrheum

22 Antiphospholipid Syndrome Poor correlation between APLS and premature atherosclerosis SLE with anti β 2 G1 antibodies have increased incidence of MI

23 Psoriasis and PsA Chronic inflammatory conditions Increased prevalence and severity of CVS in these pts

24 Systemic Sclerosis Myocardial perfusion injury- well documented in PSS Patent epicardial vessels and normal intramural coronary vessels Oral nifedipine associated with improvement in myocardial perfusion

25 Ankylosing Spondylitis Mortality fold greater in pts with AS as compared to general population

26 SjÖgren s Syndrome Endothelial dysfunction well documented in Sjogren s Syndrome Immune dysregulation Higher incidence in pts with Anti-Ro antibodies and leucopenia Unclear if Sjogren s Syndrome is an independent risk factor for premature CVD

27 Mechanisms of premature CVD TRADITIONAL AS WELL AS NON TRADITIONAL RISK FACTORS

28 Non-traditional risk factors Striking similarities noted in the inflammatory and immunologic reactions of Atherosclerosis and RA

29 Reasons for the development of CVD in RA complex Several mechanisms

30 proinfl cytokines Abn vasc repair genes Premature CVD

31 Cytotoxic T cells Antibodies to endothelial cells Steroid use Premature CVD

32 Increased levels of Pro-inflammatory cytokines TNF α IL-6 IL-17 CRP

33 Abnormal Vascular Repair circulating EPC s Quantitative and qualitative defect in EPC s in RA/SLE/PSS Imbalance between vascular damage and repair Leads to endothelial dysfunction SLE- increased apoptosis of endothelial cells

34 Atherosclerosis in Inflammatory disorders Skaggs, B. J. et al. (2012) Accelerated atherosclerosis in patients with SLE mechanisms and management Nat. Rev. Rheumatol. doi: /nrrheum

35 Genetic Polymorphism TNF receptor Type II Genetic polymorphism of PAI I Coagulation factor XIII subunit A

36 Cytotoxic T cells ed levels of CD4 + CD28 - in pts with RA These cells cause endothelial cell cytotoxicity

37 Autoantibodies To endothelial cells components Their precise role as yet unclear

38 Corticosteroids Inconsistent results from clinical trials HYPERTENSION INSULIN RESISTANCE Steroids induce LIPID Abnormalities CVD OBESITY

39 Steroids in Chronic Inflammatory Dses Exact role of steroids in the development of CVD in chronic inflammatory conditions is yet to be defined

40 Traditional risk factors Smoking Systemic Hypertension Dyslipidaemias Microalbuminuria Insulin resistance Hyperhomocysteinaemia

41 Risk Assessment and Prevention Preventive strategies to start soon after diagnosis Awareness Guidelines lacking Unanswered questions???

42 Decreasing Traditional Risk Factors Kaplan MJ (2009) Management of cardiovascular disease risk in chronic inflammatory disorders Nat Rev Rheumatol doi: /nrrheum

43 Decreasing Disease specific risk Factors Paracetamol NSAIDS : COX II vs NS NSAIDS Aggressive treatment of underlying condition Hydroxychloroquine in SLE Corticosteroids Methotrexate Biologics

44 Summary: Patients with systemic inflammatory diseases are at significantly increased risk of cardiovascular events, which contribute to the high morbidity and mortality associated with these diseases

45 Evidence suggests that rheumatoid arthritis and systemic lupus erythematosus are independent risk factors for the development of premature cardiovascular disease (CVD

46 As factors promoting premature CVD-associated mortality might be present early in the natural history of inflammatory disease, preventive strategies to decrease cardiovascular risk should start shortly after diagnosis

47 Specific guidelines need to be developed that address the management of cardiovascular risk factors in rheumatoid arthritis, systemic lupus erythematosus and potentially other inflammatory conditions

48 Recent evidence suggests that optimal treatment of inflammatory disorders could result in improvements in vascular function and lead to decreases in the risk of CVD

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55 References: 1. Fishbein, M. C. The vulnerable andunstable atherosclerotic plaque. Cardiovasc.Pathol. [doi: /j.carpath ](2008). 2. schillinger, M. et al. inflammation and carotidartery risk for atherosclerosis study(icaras). Circulation 111, (2005). 3. ridker, P. M. et al. inflammation, aspirin, and therisk of cardiovascular disease in apparently healthy men. N. Engl. J. Med. 336, (1997). 4. ridker, P. M. et al. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N. Engl. J. Med.342, (2000). 5. ross, r. Atherosclerosis is an inflammatory disease. Am. Heart J. 138, s419 s420 (1999). 6. Libby, P. inflammation in atherosclerosis. Nature 420, (2002). 7. Manzi, s. et al. Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham study. Am. J.Epidemiol. 145, (1997). 8. Maradit-Kremers, H. et al. increased unrecognized coronary heart disease andsudden deaths in rheumatoid arthritis: a population-based cohort study. Arthritis Rheu52, (2005).

56 9. solomon, D. H. et al. Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Circulation 107, (2003). 10. Avina-Zubieta, J. A. et al. risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum. 59, (2008). 11. solomon, D. H. et al. Cardiovascular risk factors in women with and without rheumatoid arthritis. Arthritis Rheum. 50, (2004). 12. sodergren, A. et al. increased incidence of and impaired prognosis after acute myocardial infarction among patients with seropositive rheumatoid arthritis. Ann. Rheum. Dis. 66, (2007). 13. Goodson, N. J. et al. Mortality in early inflammatory polyarthritis: cardiovascular mortality is increased in seropositive patients. Arthritis Rheum. 46, (2002). 14. Bergholm, r. et al. impaired responsiveness to NO in newly diagnosed patients with rheumatoid arthritis. Arterioscler. Thromb. Vasc. Biol. 22, (2002). 15. wallberg-jonsson, s. et al. Cardiovascular morbidity and mortality in patients with seropositive rheumatoid arthritis in Northern sweden. J. Rheumatol. 24, (1997). 16. Davis, J. M. et al. The presentation and outcome of heart failure in patients with rheumatoid arthritis differs from that in the general population. Arthritis Rheum. 58, (2008).

57 Thank You!