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Rheumatic fever was classically described by the saying ‘it licks the joint and bites the heart'. Barring occasional outbreaks, improved standards of living led to its currently declining incidence restricting the disease mainly to economically less privileged society.

Patients with chronic Immune mediated inflammatory diseases (IMIDs) including systemic autoimmune rheumatic diseases, on the other hand, can be ‘bitten’ at both places namely the heart and the joints in addition to ‘licks’ at many systems by their illnesses, thereby rendering them more than twice unlucky. These multisystem disorders affect more than 5% of human beings.[1] Better understanding of immunopathology led to improved treatment options and superior quality of life than ever before, but recent concerns about increased cardiovascular (CVS) morbidity and mortality in these disorders are worrisome.

The ‘heart story’ started with Rheumatoid arthritis (RA), but subsequently premature cardiac events have been either suspected or reported in Systemic lupus erythematosus (SLE), systemic sclerosis, Primary Sjogren's syndrome, myositis, overlap and undifferentiated connective tissue diseases, Antiphospholipid syndrome, vasculitic disorders, Spondyloarthropathies including Ankylosing spondylitis and psoriatic arthropathies. Life span is shortened in most of these illnesses even after disease is well controlled and cardiovascular complications are often blamed for it.[2, 3]

Many biological basis have been proposed for the link between heart and IMIDs. Apart from inflammation and its related molecules like C Reactive Protein (CRP) and pro-inflammatory cytokines, associated secondary antiphospholipid antibody syndrome, other autoantibodies like Anti Citrullinated Peptide antibody (ACPA) in RA, Anti lipoprotein lipase antibodies in SLE, various putative auto antigens, depletion of endothelial progenitor cells in RA, associated hyperhomocysteinemia, premature and accelerated atherosclerosis, altered lipid profile especially low HDL level, imbalance between nitric oxide and Asymmetric Dimethyl Arginine (ADMA)- an inhibitor of nitric oxide synthase, smoking, drugs like coxibs and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), conventional disease modifying anti rheumatoid drugs (DMARDs), immunosupressants, biologics and infections – all have been blamed at some point of time or the other for causing CVS morbidity in IMIDs.

While direct effect of inflammation causing cardiac complications in IMIDs is the most attractive theory amongst rheumatologists, controversies regarding true prevalence and nature of cardiovascular complications and the attributable risk factors do exist.[4]

This issue of IJRD has a hospital based retrospective report from New Zealand showing a rather low risk of cardiovascular events in RA: 0.64% in 1st year and 9.4% in 10 years. Similarly, the authors report mortality risk of 0.48% in 1st year and 8.16% in 10 years. Although the confounding effect of co-existing conventional risk factors and the study design are the limiting factors, there is noticeably increasing risk of cardiovascular morbidity and mortality with longer duration of disease amongst their patients in spite of treatment with traditional DMARDs, antihypertensives, antiplatelets and lipid lowering agents.

Literature too suggests that longer disease duration and higher degree of inflammation reflecting chronicity and disease activity respectively, are more likely to contribute to the ‘heart effect’. On the contrary, better control of inflammation has been reported to lessen the risk of cardiovascular complications.[5, 6]

Subclinical process, however, may start quite early in disease, as studies show silently progressing micro vascular dysfunction in IMIDs correlating strongly with early inflammatory state.[7, 8]

Evaluation for early atherosclerosis, adoption of ‘treat to target’ concept for tight control of disease to bring down CRP or preferably high-sensitivity CRP (hs-CRP) level towards normal range are measures to keep CVS complications in abeyance in RA. A similar approach may be beneficial in all IMIDs.

It is also important to recognise the fact that conventional risk factors, metabolic syndrome, drugs like coxibs and NSAIDs could provide additional hits for CVS effect in patients with IMIDs.

Finally, IMIDs may bite the heart, more so by micro vascular pathology in a silent and unsuspecting manner. There is need to establish the true prevalence and nature of cardiovascular complications in IMIDs amongst various ethnic populations by large cohort studies. Question also arises if there is a need to design multicentric large randomised trials with statins and/or antiplatelets in these illnesses?

References

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  2. References
  • 1
    Cooper GS, Bynum MLK, Somers EC (2009) Recent insights in the epidemiology of autoimmune diseases: improved prevalence estimates and understanding of clustering of diseases. J Autoimmun 33, 197207.
  • 2
    Avina-Zubieta JA, Choi HK, Sadatsafavi M, Etminan M, Esdaile JM, Lacaille D (2008) Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum (Arthritis Care & Research) 59, 16907.
  • 3
    Meune C, Emmanuel T, Trinquart L, Allanore Y (2009) Trends in cardiovascular mortality in patients with rheumatoid arthritis over 50 years: a systematic review and metaanalysis of cohort studies. Rheumatology 48, 130913.
  • 4
    Liao KP, Solomon DH (2013) Traditional cardiovascular risk factors, inflammation and cardiovascular risk in rheumatoid arthritis. Rheumatology (Oxford) 52, 4552.
  • 5
    Bisoendial RJ, Stroes ES, Tak PP (2009) Where the immune response meets the vessel wall. Neth J Med 67, 32833.
  • 6
    Galarraga B, Khan F, Kumar P, Pullar T, Belch JJ (2008) C-reactive protein: the underlying cause of micro vascular dysfunction in rheumatoid arthritis. Rheumatology (Oxford) 47, 17804.
  • 7
    Toutouzas K, Sfikakis PP, Karanasos A et al. (2013) Myocardial ischaemia without obstructive coronary artery disease in rheumatoid arthritis: hypothesis-generating insights from a cross-sectional study. Rheumatology 52, 7680.
  • 8
    Kerola AM, Kerola T, Kauppi MJ et al. (2013) Cardiovascular comorbidities antedating the diagnosis of rheumatoid arthritis. Ann Rheum Dis 72, 2116.