Kivimäki, Mika, Lawlor, Debbie A., Smith, George Davey, Kumari, Meena, Donald, Ann, Britton, A. (Annie), Casas, Juan P., Shah, Tina, Brunner, Eric, Timpson, Nicholas J., Halcox, Julian P. J., Miller, Michelle A., Humphries, Steve E., Deanfield, John, Marmot, Michael G. and Hingorani, Aroon (2008) Does high C-reactive protein concentration increase atherosclerosis? : the Whitehall II Study. PLOS One, Vol.3 (No.8). e3013. doi:10.1371/journal.pone.0003013

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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 crosssectional 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.

Item Type:	Journal Article
Subjects:	Q Science > QP Physiology R Medicine > RC Internal medicine
Divisions:	Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	C-reactive protein, Atherosclerosis -- Risk factors, Atherosclerosis -- Genetic aspects
Journal or Publication Title:	PLOS One
Publisher:	Public Library of Science
ISSN:	1932-6203
Official Date:	20 August 2008
Dates:	Date Event 20 August 2008 Published
Volume:	Vol.3
Number:	No.8
Page Range:	e3013
DOI:	10.1371/journal.pone.0003013
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
Funder:	British Academy (BA), Medical Research Council (Great Britain) (MRC), British Heart Foundation, Great Britain. Health and Safety Executive, Great Britain. Dept. of Health (DoH), National Heart, Lung, and Blood Institute, National Institute on Aging (NIA), United States. Agency for Health Care Policy and Research, John D. and Catherine T. MacArthur Foundation, Suomen Akatemia [Academy of Finland]
Grant number:	HL36310 (NHLBI), AG13196 (NIA), HS06516 (AHCPR), 117604 (SA), PG2005/014 (BHF), FS/02/086/14760 (BHF)

Data sourced from Thomson Reuters' Web of Knowledge

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