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Paradoxical Association of C-Reactive Protein with Endothelial Function in Rheumatoid Arthritis

Holmes, MV; Jiang, BY; McNeill, K; Wong, M; Oakley, SP; Kirkham, B; Chowienczyk, PJ; (2010) Paradoxical Association of C-Reactive Protein with Endothelial Function in Rheumatoid Arthritis. PLOS ONE , 5 (4) , Article e10242. 10.1371/journal.pone.0010242. Green open access

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Abstract

Background: Within the general population, levels of C-reactive protein (CRP) are positively associated with atherosclerotic cardiovascular disease (CVD). Whether CRP is causally implicated in atherogenesis or is the results of atherosclerosis is disputed. A role of CRP to protect endothelium-derived nitric oxide (EDNO) has been suggested. We examined the association of CRP with EDNO-dependent vasomotor function and subclinical measures of atherosclerosis and arteriosclerosis in patients with raised CRP resulting from rheumatoid arthritis (RA).Methodology/Principal Findings: Patients with RA (n = 59) and healthy control subjects (n = 123), underwent measures of high sensitivity CRP, flow-mediated dilation (FMD, dependent on EDNO), intima-media thickness (IMT, a measure of subclinical atherosclerosis) and aortic pulse wave velocity (PWV, a measure of arteriosclerosis). IMT and PWV were elevated in patients with RA compared to controls but FMD was similar in the two groups. In patients with RA, IMT and PWV were not correlated with CRP but FMD was positively independently correlated with CRP (P<0.01).Conclusions/Significance: These findings argue against a causal role of CRP in atherogenesis and are consistent with a protective effect of CRP on EDNO bioavailability.

Type: Article
Title: Paradoxical Association of C-Reactive Protein with Endothelial Function in Rheumatoid Arthritis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0010242
Publisher version: http://dx.doi.org/10.1371/journal.pone.0010242
Language: English
Additional information: © 2010 Holmes 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. Michael V. Holmes is funded by an Academic Clinical Fellowship from the National Institute for Health Research (NIHR). The authors acknowledge financial support from the Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: CORONARY-HEART-DISEASE, INTIMA-MEDIA THICKNESS, PULSE-WAVE VELOCITY, CARDIOVASCULAR EVENTS, NITRIC-OXIDE, CAROTID-ARTERY, OLDER-ADULTS, MYOCARDIAL-INFARCTION, VASCULAR FUNCTION, AORTIC STIFFNESS
UCL classification: UCL
URI: https://discovery.ucl.ac.uk/id/eprint/1307731
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