Are markers of inflammation more strongly associated with risk for fatal than for nonfatal vascular events?

Sattar, N.A. et al. (2009) Are markers of inflammation more strongly associated with risk for fatal than for nonfatal vascular events? PLoS Medicine, 6(6), e1000099. (doi: 10.1371/journal.pmed.1000099)

Abstract

<p><b>Background:</b> Circulating inflammatory markers may more strongly relate to risk of fatal versus nonfatal cardiovascular disease (CVD) events, but robust prospective evidence is lacking. We tested whether interleukin (IL)-6, C-reactive protein (CRP), and fibrinogen more strongly associate with fatal compared to nonfatal myocardial infarction (MI) and stroke.</p> <p><b>Methods and Findings:</b> In the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), baseline inflammatory markers in up to 5,680 men and women aged 70-82 y were related to risk for endpoints; nonfatal CVD (i.e., nonfatal MI and nonfatal stroke [n = 672]), fatal CVD (n = 190), death from other CV causes (n = 38), and non-CVD mortality (n = 300), over 3.2-y follow-up. Elevations in baseline IL-6 levels were significantly (p = 0.0009; competing risks model analysis) more strongly associated with fatal CVD (hazard ratio [HR] for 1 log unit increase in IL-6 1.75, 95% confidence interval [CI] 1.44-2.12) than with risk of nonfatal CVD (1.17, 95% CI 1.04-1.31), in analyses adjusted for treatment allocation. The findings were consistent in a fully adjusted model. These broad trends were similar for CRP and, to a lesser extent, for fibrinogen. The results were also similar in placebo and statin recipients (i.e., no interaction). The C-statistic for fatal CVD using traditional risk factors was significantly (+0.017; p<0.0001) improved by inclusion of IL-6 but not so for nonfatal CVD events (p = 0.20).</p> <p><b>Conclusions:</b> In PROSPER, inflammatory markers, in particular IL-6 and CRP, are more strongly associated with risk of fatal vascular events than nonfatal vascular events. These novel observations may have important implications for better understanding aetiology of CVD mortality, and have potential clinical relevance.</p>

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Macfarlane, Professor Peter and Welsh, Professor Paul and Stott J, Professor David and Ford, Professor Ian and Shepherd, Prof James and Lowe, Professor Gordon and Cobbe, Professor Stuart and Murray, Mrs Heather and Sattar, Professor Naveed
• Authors: Sattar, N.A., Murray, H.M., Welsh, P.I., Blauw, G.J., Buckley, B.M., Cobbe, S., de Craen, A.J.M., Lowe, G.D., Jukema, J.W., Macfarlane, P.W., Stott, D.J., Murphy, M.B., Westendorp, R.G.J., Shepherd, J., and Ford, I.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre; College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: PLoS Medicine
• Publisher: Public Library of Science
• ISSN: 1549-1277
• ISSN (Online): 1549-1277
• Published Online: 23 June 2009
• Copyright Holders: Copyright © 2009 The Authors
• First Published: First published in PLoS Medicine 6(6):e1000099
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher