Cardiovascular risk in rheumatoid arthritis: recent advances in the understanding of the pivotal role of inflammation, risk predictors and the impact of treatment

Ernest Choy, Kandeepan Ganeshalingam, Anne Grete Semb, Zoltán Szekanecz, Michael Nurmohamed, Ernest Choy, Kandeepan Ganeshalingam, Anne Grete Semb, Zoltán Szekanecz, Michael Nurmohamed

Abstract

Risk of cardiovascular (CV) disease is increased among RA patients. High inflammatory burden associated with RA appears to be a key driver of the increased cardiovascular risk. Inflammation is linked with accelerated atherosclerosis and associated with a paradoxical inversion of the relationship between CV risk and lipid levels in patients with untreated RA, recently coined the lipid paradox. Furthermore, the inflammatory burden is also associated with qualitative as well as quantitative changes in lipoproteins, with the anti-inflammatory and atheroprotective roles associated with high-density lipoprotein cholesterol significantly altered. RA therapies can increase lipid levels, which may reflect the normalization of lipids due to their inflammatory-dampening effects. However, these confounding influences of inflammation and RA therapies on lipid profiles pose challenges for assessing CV risk in RA patients and interpretation of traditional CV risk scores. In this review we examine the relationship between the increased inflammatory burden in RA and CV risk, exploring how inflammation influences lipid profiles, the impact of RA therapies and strategies for identifying and monitoring CV risk in RA patients aimed at improving CV outcomes.

Keywords: anti-rheumatic agents; atherosclerosis; cardiovascular disease; dyslipidaemias; inflammation; rheumatoid arthritis.

© The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Figures

F ig . 1
Fig. 1
Representation of the inverse relationship between changes in inflammatory and lipid parameters The paradigm by which an increase in the inflammatory burden in RA is associated with the lowering of lipid levels has also been noted in other chronic inflammatory conditions, after MI, after surgery and in cancer treatment [21, 29, 64–70]. In RA, a reduction of inflammation through treatment with traditional and/or biologic DMARDs is reflected in elevations in lipid levels [71]. Data, although limited, suggest the extent to which lipid levels change may be different between RA therapies; however, further studies are required to fully ascertain the relationship between suppression of inflammation, lipid elevations and future cardiovascular risk [71, 102]. MI, myocardial infarction.
F ig . 2
Fig. 2
Inflammation induces qualitative changes to HDL subparticle composition Systemic inflammation associated with RA may confer both quantitative and qualitative changes to HDL cholesterol underlying the loss of some anti-inflammatory and atheroprotective properties. Known changes to subparticle composition induced by inflammation are summarized in this figure [74, 76–83, 86–88]. apoA1: apolipoprotein A1; apoJ: apolipoprotein J; CETP: cholesteryl ester transfer protein; HDL: high-density lipoprotein; LCAT: lecithin cholesterol acyltransferae; LDL: low-density lipoprotein; PAF-AH: platelet-activating factor acetylhydrolase; PON-1: paraoxonase 1; SAA: serum amyloid A; sPLA2: secretory non-pancreatic phospholipase A2.
F ig . 3
Fig. 3
Impact of tight control of inflammation and disease activity in relation to the reduction of cardiovascular risk in RA The heightened inflammatory state in RA is linked with accelerated atherosclerosis, with systemic inflammation exacerbating adverse changes in both established and novel cardiovascular (CV) risk factors [16–19]. Additionally, the use of some anti-inflammatory medication is also associated with increasing CV risk [6]. Treat-to-target strategies with traditional and/or biologic DMARDs can be highly effective to rapidly reduce inflammation and achieve tight control of disease activity [146]. Lipid profiles can then be monitored and, if appropriate, treated with lipid-lowering drugs according to national guidelines [147–149].

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