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Does High C-reactive Protein Concentration Increase Atherosclerosis? The Whitehall II Study

Kivimaki, M; Lawlor, DA; Smith, GD; Kumari, M; Donald, A; Britton, A; Casas, JP; ... Hingorani, AD; + view all (2008) Does High C-reactive Protein Concentration Increase Atherosclerosis? The Whitehall II Study. PLOS ONE , 3 (8) , Article e3013. 10.1371/journal.pone.0003013. Green open access

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Abstract

Background: C-reactive protein (CRP), a marker of systemic inflammation, is associated with risk of coronary events and subclinical measures of atherosclerosis. Evidence in support of this link being causal would include an association robust to adjustments for confounders (multivariable standard regression analysis) and the association of CRP gene polymorphisms with atherosclerosis (Mendelian randomization analysis).Methodology/Principal Findings: We genotyped 3 tag single nucleotide polymorphisms (SNPs) [+ 1444T>C (rs1130864); +2303G>A (rs1205) and +4899T>G (rs 3093077)] in the CRP gene and assessed CRP and carotid intima-media thickness (CIMT), a structural marker of atherosclerosis, in 4941 men and women aged 50-74 (mean 61) years (the Whitehall II Study). The 4 major haplotypes from the SNPs were consistently associated with CRP level, but not with other risk factors that might confound the association between CRP and CIMT. CRP, assessed both at mean age 49 and at mean age 61, was associated both with CIMT in age and sex adjusted standard regression analyses and with potential confounding factors. However, the association of CRP with CIMT attenuated to the null with adjustment for confounding factors in both prospective and cross-sectional analyses. When examined using genetic variants as the instrument for serum CRP, there was no inferred association between CRP and CIMT.Conclusions/Significance: Both multivariable standard regression analysis and Mendelian randomization analysis suggest that the association of CRP with carotid atheroma indexed by CIMT may not be causal.

Type: Article
Title: Does High C-reactive Protein Concentration Increase Atherosclerosis? The Whitehall II Study
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0003013
Publisher version: http://dx.doi.org/10.1371/journal.pone.0003013
Language: English
Additional information: © 2008 Kivimäki et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The Whitehall II study has been supported by grants from the Medical Research Council; British Heart Foundation; Health and Safety Executive; Department of Health; National Heart Lung and Blood Institute (HL36310), US, NIH: National Institute on Aging (AG13196), US, NIH; Agency for Health Care Policy Research (HS06516); and the John D and Catherine T MacArthur Foundation Research Networks on Successful Midlife Development and Socio-economic Status and Health. Mi.K. is supported by the Academy of Finland (Projects no. 117604), D.A.L. by a UK Department of Health Career Scientist Award, M.G.M. by a MRC Research Professorship. A.D.H. holds a British Heart Foundation Senior Research Fellowship, and S.E.H. and J.E.D. received Chair support from the British Heart Foundation (BHF). S.E.H. and T.S. are supported by the BHF (PG2005/014 and (FS/02/086/14760). Funders had no role in the design and conduct of the study, in the collection, analysis, interpretation of the data, or in the preparation, review, or approval of the manuscript.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Clinical Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health > Epidemiology and Public Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics
URI: https://discovery.ucl.ac.uk/id/eprint/179282
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