C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis

Amanda J Lee, Emerging risk factors collaboration

Research output: Contribution to journalArticle

1236 Citations (Scopus)

Abstract

BACKGROUND: Associations of C-reactive protein (CRP) concentration with risk of major diseases can best be assessed by long-term prospective follow-up of large numbers of people. We assessed the associations of CRP concentration with risk of vascular and non-vascular outcomes under different circumstances. METHODS: We meta-analysed individual records of 160 309 people without a history of vascular disease (ie, 1.31 million person-years at risk, 27 769 fatal or non-fatal disease outcomes) from 54 long-term prospective studies. Within-study regression analyses were adjusted for within-person variation in risk factor levels. RESULTS: Log(e) CRP concentration was linearly associated with several conventional risk factors and inflammatory markers, and nearly log-linearly with the risk of ischaemic vascular disease and non-vascular mortality. Risk ratios (RRs) for coronary heart disease per 1-SD higher log(e) CRP concentration (three-fold higher) were 1.63 (95% CI 1.51-1.76) when initially adjusted for age and sex only, and 1.37 (1.27-1.48) when adjusted further for conventional risk factors; 1.44 (1.32-1.57) and 1.27 (1.15-1.40) for ischaemic stroke; 1.71 (1.53-1.91) and 1.55 (1.37-1.76) for vascular mortality; and 1.55 (1.41-1.69) and 1.54 (1.40-1.68) for non-vascular mortality. RRs were largely unchanged after exclusion of smokers or initial follow-up. After further adjustment for fibrinogen, the corresponding RRs were 1.23 (1.07-1.42) for coronary heart disease; 1.32 (1.18-1.49) for ischaemic stroke; 1.34 (1.18-1.52) for vascular mortality; and 1.34 (1.20-1.50) for non-vascular mortality. INTERPRETATION: CRP concentration has continuous associations with the risk of coronary heart disease, ischaemic stroke, vascular mortality, and death from several cancers and lung disease that are each of broadly similar size. The relevance of CRP to such a range of disorders is unclear. Associations with ischaemic vascular disease depend considerably on conventional risk factors and other markers of inflammation. FUNDING: British Heart Foundation, UK Medical Research Council, BUPA Foundation, and GlaxoSmithKline.
Original languageEnglish
Pages (from-to)132-140
Number of pages9
JournalThe Lancet
Volume375
Issue number9709
Early online date22 Dec 2009
DOIs
Publication statusPublished - 9 Jan 2010

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C-Reactive Protein
Coronary Disease
Meta-Analysis
Stroke
Blood Vessels
Mortality
Vascular Diseases
Odds Ratio
Fibrinogen
Lung Diseases
Biomedical Research
Lung Neoplasms
Regression Analysis
Prospective Studies
Inflammation

Keywords

  • alcohol drinking
  • biological markers
  • blood pressure
  • body mass index
  • c-reactive protein
  • cholesterol
  • coronary disease
  • databases, factual
  • Diabetes mellitus
  • female
  • fibrinogen
  • humans
  • interleukin-6
  • leukocyte count
  • lung diseases
  • male
  • middle aged
  • motor activity
  • neoplasms
  • regression analysis
  • risk assessment
  • risk factors
  • serum albumin
  • sex factors
  • smoking
  • stroke
  • triglycerides

Cite this

C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality : an individual participant meta-analysis. / Lee, Amanda J; Emerging risk factors collaboration.

In: The Lancet, Vol. 375, No. 9709, 09.01.2010, p. 132-140.

Research output: Contribution to journalArticle

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T1 - C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality

T2 - an individual participant meta-analysis

AU - Lee, Amanda J

AU - Emerging risk factors collaboration

N1 - Copyright 2010 Elsevier Ltd. All rights reserved.

PY - 2010/1/9

Y1 - 2010/1/9

N2 - BACKGROUND: Associations of C-reactive protein (CRP) concentration with risk of major diseases can best be assessed by long-term prospective follow-up of large numbers of people. We assessed the associations of CRP concentration with risk of vascular and non-vascular outcomes under different circumstances. METHODS: We meta-analysed individual records of 160 309 people without a history of vascular disease (ie, 1.31 million person-years at risk, 27 769 fatal or non-fatal disease outcomes) from 54 long-term prospective studies. Within-study regression analyses were adjusted for within-person variation in risk factor levels. RESULTS: Log(e) CRP concentration was linearly associated with several conventional risk factors and inflammatory markers, and nearly log-linearly with the risk of ischaemic vascular disease and non-vascular mortality. Risk ratios (RRs) for coronary heart disease per 1-SD higher log(e) CRP concentration (three-fold higher) were 1.63 (95% CI 1.51-1.76) when initially adjusted for age and sex only, and 1.37 (1.27-1.48) when adjusted further for conventional risk factors; 1.44 (1.32-1.57) and 1.27 (1.15-1.40) for ischaemic stroke; 1.71 (1.53-1.91) and 1.55 (1.37-1.76) for vascular mortality; and 1.55 (1.41-1.69) and 1.54 (1.40-1.68) for non-vascular mortality. RRs were largely unchanged after exclusion of smokers or initial follow-up. After further adjustment for fibrinogen, the corresponding RRs were 1.23 (1.07-1.42) for coronary heart disease; 1.32 (1.18-1.49) for ischaemic stroke; 1.34 (1.18-1.52) for vascular mortality; and 1.34 (1.20-1.50) for non-vascular mortality. INTERPRETATION: CRP concentration has continuous associations with the risk of coronary heart disease, ischaemic stroke, vascular mortality, and death from several cancers and lung disease that are each of broadly similar size. The relevance of CRP to such a range of disorders is unclear. Associations with ischaemic vascular disease depend considerably on conventional risk factors and other markers of inflammation. FUNDING: British Heart Foundation, UK Medical Research Council, BUPA Foundation, and GlaxoSmithKline.

AB - BACKGROUND: Associations of C-reactive protein (CRP) concentration with risk of major diseases can best be assessed by long-term prospective follow-up of large numbers of people. We assessed the associations of CRP concentration with risk of vascular and non-vascular outcomes under different circumstances. METHODS: We meta-analysed individual records of 160 309 people without a history of vascular disease (ie, 1.31 million person-years at risk, 27 769 fatal or non-fatal disease outcomes) from 54 long-term prospective studies. Within-study regression analyses were adjusted for within-person variation in risk factor levels. RESULTS: Log(e) CRP concentration was linearly associated with several conventional risk factors and inflammatory markers, and nearly log-linearly with the risk of ischaemic vascular disease and non-vascular mortality. Risk ratios (RRs) for coronary heart disease per 1-SD higher log(e) CRP concentration (three-fold higher) were 1.63 (95% CI 1.51-1.76) when initially adjusted for age and sex only, and 1.37 (1.27-1.48) when adjusted further for conventional risk factors; 1.44 (1.32-1.57) and 1.27 (1.15-1.40) for ischaemic stroke; 1.71 (1.53-1.91) and 1.55 (1.37-1.76) for vascular mortality; and 1.55 (1.41-1.69) and 1.54 (1.40-1.68) for non-vascular mortality. RRs were largely unchanged after exclusion of smokers or initial follow-up. After further adjustment for fibrinogen, the corresponding RRs were 1.23 (1.07-1.42) for coronary heart disease; 1.32 (1.18-1.49) for ischaemic stroke; 1.34 (1.18-1.52) for vascular mortality; and 1.34 (1.20-1.50) for non-vascular mortality. INTERPRETATION: CRP concentration has continuous associations with the risk of coronary heart disease, ischaemic stroke, vascular mortality, and death from several cancers and lung disease that are each of broadly similar size. The relevance of CRP to such a range of disorders is unclear. Associations with ischaemic vascular disease depend considerably on conventional risk factors and other markers of inflammation. FUNDING: British Heart Foundation, UK Medical Research Council, BUPA Foundation, and GlaxoSmithKline.

KW - alcohol drinking

KW - biological markers

KW - blood pressure

KW - body mass index

KW - c-reactive protein

KW - cholesterol

KW - coronary disease

KW - databases, factual

KW - Diabetes mellitus

KW - female

KW - fibrinogen

KW - humans

KW - interleukin-6

KW - leukocyte count

KW - lung diseases

KW - male

KW - middle aged

KW - motor activity

KW - neoplasms

KW - regression analysis

KW - risk assessment

KW - risk factors

KW - serum albumin

KW - sex factors

KW - smoking

KW - stroke

KW - triglycerides

U2 - 10.1016/S0140-6736(09)61717-7

DO - 10.1016/S0140-6736(09)61717-7

M3 - Article

VL - 375

SP - 132

EP - 140

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 9709

ER -