Inflammatory biomarkers and the prediction of coronary events among people at intermediate risk: the EPIC-Norfolk prospective population study
- J S Rana1,2,
- M Cote3,
- J-P Després3,
- M S Sandhu4,
- P J Talmud5,
- E Ninio6,
- N J Wareham7,
- J J P Kastelein2,
- A H Zwinderman8,
- K-T Khaw4,
- S M Boekholdt2,9
- 1Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, David Geffen School of Medicine at University of California, Los Angeles, USA
- 2Department of Vascular Medicine, Academic Medical Centre, Amsterdam, The Netherlands
- 3Québec Heart Institute, Hôpital Laval Research Centre, Québec, Canada
- 4Institute of Public Health and Primary Care, University of Cambridge, Cambridge, UK
- 5Division of Cardiovascular Genetics, Royal Free and University College Medical School, London, UK
- 6INSERM UMRS525; UPMC Univ Paris 06 and Faculté de Médecine Pierre et Marie Curie, Paris, France
- 7Medical Research Council, Epidemiology Unit, Cambridge, UK
- 8Department of Clinical Epidemiology and Biostatistics, Academic Medical Centre, Amsterdam, The Netherlands
- 9Department of Cardiology, Academic Medical Centre, Amsterdam, The Netherlands
- Correspondence to Dr S M Boekholdt, Academic Medical Centre, Department of Cardiology, F4-159.2, PO Box 22660, 1100 DD Amsterdam, The Netherlands;
- Accepted 30 June 2009
- Published Online First 8 July 2009
Objective: To evaluate the role of the inflammatory biomarkers C-reactive protein (CRP), myeloperoxidase, paraoxonase, secretory phospholipase A2 group IIA (sPLA2), lipoprotein-associated phospholipase A2, fibrinogen, macrophage chemoattractant protein-1 and adiponectin, in predicting the risk of coronary heart disease (CHD) among people estimated to be at intermediate risk according to the Framingham Risk Score (FRS).
Design: Prospective case–control study nested in EPIC-Norfolk cohort.
Setting: Norfolk, UK.
Patients: Apparently healthy men and women aged 45–79 years.
Main outcome measures: Risk of future coronary artery disease.
Results: For participants predicted to be at intermediate risk by the FRS, the highest c statistics were observed for FRS plus CRP (0.61, 95% CI 0.57 to 0.65) and for FRS plus sPLA2 (0.56, 95% CI 0.52 to 0.6). Net correct reclassification of cases and controls for each marker was assessed for people across the entire risk spectrum and again for people at intermediate risk only. The largest differences were observed for CRP, 12.0% net reclassification improvement in the entire risk spectrum and 28.4% net reclassification improvement in the intermediate-risk group and for sPLA2, the net reclassification improvement was 6.4% in the entire risk spectrum and 16.3% in the intermediate-risk group.
Conclusions: The discriminatory potential of inflammatory biomarkers was substantially different when analysed across the entire risk spectrum compared with the subgroup of people at intermediate risk.
Funding EPIC-Norfolk is supported by program grants from the Medical Research Council UK and Cancer Research UK and with additional support from the European Union, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency and the Wellcome Trust. PJT is supported by the British Heart Foundation (PG2005/014). Part of this work was supported by the Institut National de la Santé et de la Recherche Médicale.
Competing interests None.
Provenance and Peer review Not commissioned; externally peer reviewed.
Ethics approval Approval from the Norwich District Health Authority ethics committee.
The funding sources had no role in study design, conduct, analysis and decision to submit the manuscript for publication.