Journal
EUROPEAN JOURNAL OF EPIDEMIOLOGY
Volume 36, Issue 1, Pages 11-36Publisher
SPRINGER
DOI: 10.1007/s10654-020-00681-w
Keywords
Umbrella review; Meta-analysis; Systematic review; C-reactive protein; CRP; Mendelian randomization; Bias
Categories
Funding
- CRUK Career Development Fellowship [C31250/A22804]
- Wellcome Trust
Ask authors/readers for more resources
Despite extensive research on C-reactive protein (CRP) and its association with numerous non-infectious diseases, convincing evidence for associations and causal effects with chronic health outcomes remains limited. Meta-analyses and Mendelian randomization studies have identified some relationships, but the majority show heterogeneity, small study effects, or excess significance, highlighting the need for further research in this area.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available