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Annals of the Rheumatic Diseases 2009;68:460-469; doi:10.1136/ard.2008.101964
Copyright © 2009 BMJ Publishing Group Ltd & European League Against Rheumatism.

REVIEW

Interpreting lipid levels in the context of high-grade inflammatory states with a focus on rheumatoid arthritis: a challenge to conventional cardiovascular risk actions

E Choy1, N Sattar2

1 Sir Alfred Baring Garrod Clinical Trials Unit, Academic Department of Rheumatology, King’s College, London, UK
2 BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Scotland, UK

Correspondence to:
Naveed Sattar, Professor of Metabolic Medicine, Faculty of Medicine, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK; nsattar{at}clinmed.gla.ac.uk

In severe untreated rheumatoid arthritis (RA), reductions in high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol and total cholesterol have been noted; this is in line with findings in other pathologies/conditions associated with inflammation or infection, such as sepsis, cancer, trauma or the postoperative period. Although the precise mechanisms remain to be established, cytokine-induced activation of the reticuloendothelial system is potentially critical to such changes. Consequently, dampening of inflammation in severe RA—as occurs with several biologics—may lead to increases, not only in high-density lipoprotein-cholesterol, but also with other lipid moieties, including total and low-density lipoprotein-cholesterol and, perhaps, triglycerides. This concept is consistent with findings following antitumour necrosis factor treatment and interleukin-6 receptor inhibition in patients with RA. At the same time, it is increasingly apparent that potent dampening of inflammation, however achieved, broadly reduces the risk of cardiovascular disease in RA. Therefore, changes in lipid profiles, particularly increases in cholesterol and triglycerides that occur with treatments for severe inflammation, may not represent increased cardiovascular risk as in the usual understanding of lipid-level elevations in individuals without significant inflammation. Rather, changes in lipid levels, in part or largely, may represent a predictable response to attenuation of inflammation. These observations are increasingly important clinically and should aid in the understanding and interpretation of lipid changes under inflammatory conditions, as well as in the context of potent anti-inflammatory interventions.


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