Does high C-reactive protein concentration increase atherosclerosis? : the Whitehall II Study
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., Dr., 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. ISSN 1932-6203
WRAP_MIller_journal.pone.0003013.pdf - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Official URL: http://dx.doi.org/10.1371/journal.pone.0003013
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 > Translational & Systems Medicine > Metabolic and Vascular Health
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|
|Official Date:||20 August 2008|
|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)|
1. Verma S, Devaraj S, Jialal I (2006) Is C-reactive protein an innocent bystander
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