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Seventeen year risk of all-cause and cause-specific mortality associated with C-reactive protein, fibrinogen and leukocyte count in men and women: the EPIC-Norfolk study

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Abstract

There is strong evidence from observational studies suggesting serum C-reactive protein (CRP) is associated with cardiovascular and all-cause mortality. However, less is known about whether there are differences in the association of CRP with all-cause or cause specific mortality by sex, smoking, body mass index (BMI), or physical activity. We aimed to investigate these interactions and also investigate and compare the association of CRP and other inflammation markers (i.e., fibrinogen and leukocyte count) with all-cause and cause-specific mortality. Men and women aged 40–79 were recruited in 1993–1997 in the EPIC-Norfolk cohort study. A total of 16,850 participants with high-sensitivity assayed CRP data who had no known cancer, myocardial infarction and stroke at baseline were entered in the analysis to test the association of CRP, fibrinogen and leukocyte count with risk of all-cause and cause specific mortality. A total of, 2,603 all-cause deaths (1,452 in men) including 823 cardiovascular and 1,035 cancer deaths, were observed after 231,000 person-years of follow-up (median 14.3 years). CRP was positively associated with risk of all-cause, cardiovascular, and non-cancer non-cardiovascular mortality independent of established risk factors. The hazard ratio of all-cause mortality (95 % CI) for participants with CRP in the range of 3–10 and >10 mg/l (vs. <0.5 mg/l) was 1.56 (1.26–1.93) and 1.87 (1.43–2.43) respectively in men and 1.34 (1.07–1.68) and 1.98 (1.50–2.63) in women. The association was less positively graded in women with the increased risk being significant only at higher levels of the CRP distribution. The association persisted in never smokers and did not vary by levels of BMI or physical activity. Although fibrinogen and leukocyte count were also positively associated with mortality risk, only CRP remained a significant predictor of mortality when the inflammation markers were adjusted for one another in multivariable models. Serum CRP levels were a long-term predictor of risk of cardiovascular and non-cardiovascular mortality independent of known risk factors, fibrinogen, and leukocyte count.

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Acknowledgments

We thank all study participants, general practitioners and the EPIC-Norfolk study team for their contribution. The EPIC-Norfolk study is supported by funding from the Medical Research Council and Cancer Research UK with additional support from the Stroke Association, British Heart Foundation, Research into Ageing, and the Academy of Medical Science. S.A. is supported by the Gates Cambridge scholarship. Funding sources did not have a role in the design and conduct of the study, the collection, management, analysis, and interpretation of the data or the preparation, review, approval, or decision to submit the manuscript. S.A. analysed the data and wrote the manuscript with co-authors. R.L. performed all data management and record linkage. KTK and NJW are principal investigators in the EPIC-Norfolk population study. All authors provided detailed comments on the manuscript, reviewed and edited the manuscript and contributed to the discussion.

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The authors declare that there is no conflict of interest associated with this manuscript.

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Authors and Affiliations

  1. Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, CB1 8RN, UK

    Sara Ahmadi-Abhari & Robert N. Luben

  2. MRC Epidemiology Unit, Institute of Metabolic Sciences, Cambridge, UK

    Nicholas J. Wareham

  3. Department of Public Health and Primary Care, Clinical Gerontology Unit, Addenbrooke’s Hospital, Hills Road, Cambridge, CB2 2QQ, UK

    Kay-Tee Khaw

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  1. Sara Ahmadi-Abhari
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Correspondence to Sara Ahmadi-Abhari.

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Ahmadi-Abhari, S., Luben, R.N., Wareham, N.J. et al. Seventeen year risk of all-cause and cause-specific mortality associated with C-reactive protein, fibrinogen and leukocyte count in men and women: the EPIC-Norfolk study. Eur J Epidemiol 28, 541–550 (2013). https://doi.org/10.1007/s10654-013-9819-6

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