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Inflammation, glucocorticoids and risk of cardiovascular disease

Nature Clinical Practice Rheumatology volume 5, pages 18–19 (2009)Cite this article

Cardiovascular disease is the leading cause of death and hospitalization in both sexes in many countries, and its association with traditional risk factors, such as cigarette smoking, high blood pressure and obesity, is well-known. An important concern of clinical research is, therefore, to identify non-traditional cardiovascular risk factors in order to intensify preventive measures. It has become increasingly clear that inflammation has a substantial role in the development of cardiovascular disease among the general population. Furthermore, it is known that chronic inflammatory diseases convey an additional increase in the risk of cardiovascular disease. Treatments that reduce inflammation, therefore, aim to reduce this risk; however, glucocorticoids can convey a considerable cardiovascular risk themselves. The challenge for rheumatologists, therefore, is to determine the relative benefits and risks of glucocorticoid treatment for inflammatory diseases.

In this regard, an interesting and clinically important concern is to determine which individuals might benefit from anti-inflammatory treatment, and to what extent. Proinflammatory status obviously differs among individuals. A large, long-term, population-based prospective study by van den Akker et al.1 found that the glucocorticoid receptor gene haplotype 3, a common variant that leads to increased expression of the glucocorticoid receptor β splice, was associated with significantly increased risks of both myocardial infarction and coronary heart disease. This variant is thought to have a dominant negative effect on the glucocorticoid receptor α—the receptor type that mediates most of the anti-inflammatory and immunosuppressive effects of glucocorticoids—thereby leading to relative glucocorticoid resistance and, ultimately, to a more active immune system. Accordingly, the authors also found higher levels of C-reactive protein and interleukin 6 and increased carotid intima–media thickness in persons homozygous for haplotype 3. They concluded, therefore, that genetically determined reductions in cortisol sensitivity could be involved in the pathogenesis of cardiovascular disease. The data from this study raise the question of whether it is possible to identify a high-risk subgroup of the general population that might benefit from anti-inflammatory treatment.

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Authors and Affiliations

  1. F Buttgereit is Professor of Rheumatology and G-R Burmester is Professor of Medicine in the Department of Rheumatology and Clinical Immunology, Charité University Medicine, Berlin, Germany.,

    Frank Buttgereit & Gerd-Rüdiger Burmester

  2. BJ Lipworth is Professor of Allergy and Respiratory Medicine and Head of the Asthma and Allergy Research Group in the Department of Clinical Pharmacology and Therapeutics, University of Dundee School of Medicine, Dundee, Scotland, UK.,

    Brian J Lipworth

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  1. Frank Buttgereit
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  2. Gerd-Rüdiger Burmester
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Correspondence to Frank Buttgereit.

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Buttgereit, F., Burmester, GR. & Lipworth, B. Inflammation, glucocorticoids and risk of cardiovascular disease. Nat Rev Rheumatol 5, 18–19 (2009). https://doi.org/10.1038/ncprheum0963

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