Cargando…
Serum uric acid levels and multiple health outcomes: umbrella review of evidence from observational studies, randomised controlled trials, and Mendelian randomisation studies
Objective To map the diverse health outcomes associated with serum uric acid (SUA) levels. Design Umbrella review. Data sources Medline, Embase, Cochrane Database of Systematic Reviews, and screening of citations and references. Eligibility criteria Systematic reviews and meta-analyses of observatio...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group Ltd.
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5461476/ https://www.ncbi.nlm.nih.gov/pubmed/28592419 http://dx.doi.org/10.1136/bmj.j2376 |
_version_ | 1783242338559066112 |
---|---|
author | Li, Xue Meng, Xiangrui Timofeeva, Maria Tzoulaki, Ioanna Tsilidis, Konstantinos K Ioannidis, P A Campbell, Harry Theodoratou, Evropi |
author_facet | Li, Xue Meng, Xiangrui Timofeeva, Maria Tzoulaki, Ioanna Tsilidis, Konstantinos K Ioannidis, P A Campbell, Harry Theodoratou, Evropi |
author_sort | Li, Xue |
collection | PubMed |
description | Objective To map the diverse health outcomes associated with serum uric acid (SUA) levels. Design Umbrella review. Data sources Medline, Embase, Cochrane Database of Systematic Reviews, and screening of citations and references. Eligibility criteria Systematic reviews and meta-analyses of observational studies that examined associations between SUA level and health outcomes, meta-analyses of randomised controlled trials that investigated health outcomes related to SUA lowering treatment, and Mendelian randomisation studies that explored the causal associations of SUA level with health outcomes. Results 57 articles reporting 15 systematic reviews and144 meta-analyses of observational studies (76 unique outcomes), 8 articles reporting 31 meta-analyses of randomised controlled trials (20 unique outcomes), and 36 articles reporting 107 Mendelian randomisation studies (56 unique outcomes) met the eligibility criteria. Across all three study types, 136 unique health outcomes were reported. 16 unique outcomes in meta-analyses of observational studies had P<10(-6), 8 unique outcomes in meta-analyses of randomised controlled trials had P<0.001, and 4 unique outcomes in Mendelian randomisation studies had P<0.01. Large between study heterogeneity was common (80% and 45% in meta-analyses of observational studies and of randomised controlled trials, respectively). 42 (55%) meta-analyses of observational studies and 7 (35%) meta-analyses of randomised controlled trials showed evidence of small study effects or excess significance bias. No associations from meta-analyses of observational studies were classified as convincing; five associations were classified as highly suggestive (increased risk of heart failure, hypertension, impaired fasting glucose or diabetes, chronic kidney disease, coronary heart disease mortality with high SUA levels). Only one outcome from randomised controlled trials (decreased risk of nephrolithiasis recurrence with SUA lowering treatment) had P<0.001, a 95% prediction interval excluding the null, and no large heterogeneity or bias. Only one outcome from Mendelian randomisation studies (increased risk of gout with high SUA levels) presented convincing evidence. Hypertension and chronic kidney disease showed concordant evidence in meta-analyses of observational studies, and in some (but not all) meta-analyses of randomised controlled trials with respective intermediate or surrogate outcomes, but they were not statistically significant in Mendelian randomisation studies. Conclusion Despite a few hundred systematic reviews, meta-analyses, and Mendelian randomisation studies exploring 136 unique health outcomes, convincing evidence of a clear role of SUA level only exists for gout and nephrolithiasis. |
format | Online Article Text |
id | pubmed-5461476 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BMJ Publishing Group Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-54614762017-06-12 Serum uric acid levels and multiple health outcomes: umbrella review of evidence from observational studies, randomised controlled trials, and Mendelian randomisation studies Li, Xue Meng, Xiangrui Timofeeva, Maria Tzoulaki, Ioanna Tsilidis, Konstantinos K Ioannidis, P A Campbell, Harry Theodoratou, Evropi BMJ Research Objective To map the diverse health outcomes associated with serum uric acid (SUA) levels. Design Umbrella review. Data sources Medline, Embase, Cochrane Database of Systematic Reviews, and screening of citations and references. Eligibility criteria Systematic reviews and meta-analyses of observational studies that examined associations between SUA level and health outcomes, meta-analyses of randomised controlled trials that investigated health outcomes related to SUA lowering treatment, and Mendelian randomisation studies that explored the causal associations of SUA level with health outcomes. Results 57 articles reporting 15 systematic reviews and144 meta-analyses of observational studies (76 unique outcomes), 8 articles reporting 31 meta-analyses of randomised controlled trials (20 unique outcomes), and 36 articles reporting 107 Mendelian randomisation studies (56 unique outcomes) met the eligibility criteria. Across all three study types, 136 unique health outcomes were reported. 16 unique outcomes in meta-analyses of observational studies had P<10(-6), 8 unique outcomes in meta-analyses of randomised controlled trials had P<0.001, and 4 unique outcomes in Mendelian randomisation studies had P<0.01. Large between study heterogeneity was common (80% and 45% in meta-analyses of observational studies and of randomised controlled trials, respectively). 42 (55%) meta-analyses of observational studies and 7 (35%) meta-analyses of randomised controlled trials showed evidence of small study effects or excess significance bias. No associations from meta-analyses of observational studies were classified as convincing; five associations were classified as highly suggestive (increased risk of heart failure, hypertension, impaired fasting glucose or diabetes, chronic kidney disease, coronary heart disease mortality with high SUA levels). Only one outcome from randomised controlled trials (decreased risk of nephrolithiasis recurrence with SUA lowering treatment) had P<0.001, a 95% prediction interval excluding the null, and no large heterogeneity or bias. Only one outcome from Mendelian randomisation studies (increased risk of gout with high SUA levels) presented convincing evidence. Hypertension and chronic kidney disease showed concordant evidence in meta-analyses of observational studies, and in some (but not all) meta-analyses of randomised controlled trials with respective intermediate or surrogate outcomes, but they were not statistically significant in Mendelian randomisation studies. Conclusion Despite a few hundred systematic reviews, meta-analyses, and Mendelian randomisation studies exploring 136 unique health outcomes, convincing evidence of a clear role of SUA level only exists for gout and nephrolithiasis. BMJ Publishing Group Ltd. 2017-06-07 /pmc/articles/PMC5461476/ /pubmed/28592419 http://dx.doi.org/10.1136/bmj.j2376 Text en Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Research Li, Xue Meng, Xiangrui Timofeeva, Maria Tzoulaki, Ioanna Tsilidis, Konstantinos K Ioannidis, P A Campbell, Harry Theodoratou, Evropi Serum uric acid levels and multiple health outcomes: umbrella review of evidence from observational studies, randomised controlled trials, and Mendelian randomisation studies |
title | Serum uric acid levels and multiple health outcomes: umbrella review of evidence from observational studies, randomised controlled trials, and Mendelian randomisation studies |
title_full | Serum uric acid levels and multiple health outcomes: umbrella review of evidence from observational studies, randomised controlled trials, and Mendelian randomisation studies |
title_fullStr | Serum uric acid levels and multiple health outcomes: umbrella review of evidence from observational studies, randomised controlled trials, and Mendelian randomisation studies |
title_full_unstemmed | Serum uric acid levels and multiple health outcomes: umbrella review of evidence from observational studies, randomised controlled trials, and Mendelian randomisation studies |
title_short | Serum uric acid levels and multiple health outcomes: umbrella review of evidence from observational studies, randomised controlled trials, and Mendelian randomisation studies |
title_sort | serum uric acid levels and multiple health outcomes: umbrella review of evidence from observational studies, randomised controlled trials, and mendelian randomisation studies |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5461476/ https://www.ncbi.nlm.nih.gov/pubmed/28592419 http://dx.doi.org/10.1136/bmj.j2376 |
work_keys_str_mv | AT lixue serumuricacidlevelsandmultiplehealthoutcomesumbrellareviewofevidencefromobservationalstudiesrandomisedcontrolledtrialsandmendelianrandomisationstudies AT mengxiangrui serumuricacidlevelsandmultiplehealthoutcomesumbrellareviewofevidencefromobservationalstudiesrandomisedcontrolledtrialsandmendelianrandomisationstudies AT timofeevamaria serumuricacidlevelsandmultiplehealthoutcomesumbrellareviewofevidencefromobservationalstudiesrandomisedcontrolledtrialsandmendelianrandomisationstudies AT tzoulakiioanna serumuricacidlevelsandmultiplehealthoutcomesumbrellareviewofevidencefromobservationalstudiesrandomisedcontrolledtrialsandmendelianrandomisationstudies AT tsilidiskonstantinosk serumuricacidlevelsandmultiplehealthoutcomesumbrellareviewofevidencefromobservationalstudiesrandomisedcontrolledtrialsandmendelianrandomisationstudies AT ioannidispa serumuricacidlevelsandmultiplehealthoutcomesumbrellareviewofevidencefromobservationalstudiesrandomisedcontrolledtrialsandmendelianrandomisationstudies AT campbellharry serumuricacidlevelsandmultiplehealthoutcomesumbrellareviewofevidencefromobservationalstudiesrandomisedcontrolledtrialsandmendelianrandomisationstudies AT theodoratouevropi serumuricacidlevelsandmultiplehealthoutcomesumbrellareviewofevidencefromobservationalstudiesrandomisedcontrolledtrialsandmendelianrandomisationstudies |