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Global assessment of C-reactive protein and health-related outcomes: an umbrella review of evidence from observational studies and Mendelian randomization studies.

Markozannes, G; Koutsioumpa, C; Cividini, S; Monori, G; Tsilidis, KK; Kretsavos, N; Theodoratou, E; Gill, D; Ioannidis, JP; Tzoulaki, I (2021) Global assessment of C-reactive protein and health-related outcomes: an umbrella review of evidence from observational studies and Mendelian randomization studies. Eur J Epidemiol, 36 (1). pp. 11-36. ISSN 1573-7284 https://doi.org/10.1007/s10654-020-00681-w
SGUL Authors: Gill, Dipender Preet Singh

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Abstract

C-reactive protein (CRP) has been studied extensively for association with a large number of non-infectious diseases and outcomes. We aimed to evaluate the breadth and validity of associations between CRP and non-infectious, chronic health outcomes and biomarkers. We conducted an umbrella review of systematic reviews and meta-analyses and a systematic review of Mendelian randomization (MR) studies. PubMed, Scopus, and Cochrane Database of Systematic Reviews were systematically searched from inception up to March 2019. Meta-analyses of observational studies and MR studies examining associations between CRP and health outcomes were identified, excluding studies on the diagnostic value of CRP for infections. We found 113 meta-analytic comparisons of observational studies and 196 MR analyses, covering a wide range of outcomes. The overwhelming majority of the meta-analyses of observational studies reported a nominally statistically significant result (95/113, 84.1%); however, the majority of the meta-analyses displayed substantial heterogeneity (47.8%), small study effects (39.8%) or excess significance (41.6%). Only two outcomes, cardiovascular mortality and venous thromboembolism, showed convincing evidence of association with CRP levels. When examining the MR literature, we found MR studies for 53/113 outcomes examined in the observational study meta-analyses but substantial support for a causal association with CRP was not observed for any phenotype. Despite the striking amount of research on CRP, convincing evidence for associations and causal effects is remarkably limited.

Item Type: Article
Additional Information: © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Keywords: Bias, C-reactive protein, CRP, Mendelian randomization, Meta-analysis, Systematic review, Umbrella review, 1117 Public Health and Health Services, Epidemiology
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Eur J Epidemiol
ISSN: 1573-7284
Language: eng
Dates:
DateEvent
January 2021Published
25 September 2020Published Online
25 August 2020Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
C31250/A22804Cancer Research UKhttp://dx.doi.org/10.13039/501100000289
UNSPECIFIEDWellcome Trusthttp://dx.doi.org/10.13039/100004440
PubMed ID: 32978716
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/112772
Publisher's version: https://doi.org/10.1007/s10654-020-00681-w

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