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



Markozannes, Georgios, Koutsioumpa, Charalampia, Cividini, Sofia ORCID: 0000-0003-2705-9224, Monori, Grace, Tsilidis, Konstantinos K, Kretsavos, Nikolaos, Theodoratou, Evropi, Gill, Dipender, Ioannidis, John PA and Tzoulaki, Ioanna
(2020) Global assessment of C-reactive protein and health-related outcomes: an umbrella review of evidence from observational studies and Mendelian randomization studies. European Journal of Epidemiology.

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Abstract

<jats:title>Abstract</jats:title> <jats:p>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.</jats:p>

Item Type: Article
Depositing User: Symplectic Admin
Date Deposited: 30 Sep 2020 08:29
Last Modified: 07 Jun 2021 03:11
DOI: 10.1007/s10654-020-00681-w
URI: https://livrepository.liverpool.ac.uk/id/eprint/3102992