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Serum uric acid levels and multiple health outcomes: umbrella review of evidence from observational studies, randomised controlled trials, and Mendelian randomisation studies.

Abstract 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.
PMID
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Authors

Mayor MeshTerms
Keywords
Journal Title bmj (clinical research ed.)
Publication Year Start



 

PMID- 28592419
OWN - NLM
STAT- MEDLINE
DA  - 20170608
DCOM- 20170619
LR  - 20170619
IS  - 1756-1833 (Electronic)
IS  - 0959-535X (Linking)
VI  - 357
DP  - 2017 Jun 07
TI  - Serum uric acid levels and multiple health outcomes: umbrella review of evidence 
      from observational studies, randomised controlled trials, and Mendelian
      randomisation studies.
PG  - j2376
LID - 10.1136/bmj.j2376 [doi]
AB  - 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&lt;10-6, 8 unique outcomes 
      in meta-analyses of randomised controlled trials had P&lt;0.001, and 4 unique
      outcomes in Mendelian randomisation studies had P&lt;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&lt;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.
CI  - 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.
FAU - Li, Xue
AU  - Li X
AD  - Centre for Global Health Research, Usher Institute of Population Health Sciences 
      and Informatics, University of Edinburgh, Edinburgh EH8 9AG, UK.
FAU - Meng, Xiangrui
AU  - Meng X
AD  - Centre for Global Health Research, Usher Institute of Population Health Sciences 
      and Informatics, University of Edinburgh, Edinburgh EH8 9AG, UK.
FAU - Timofeeva, Maria
AU  - Timofeeva M
AD  - Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit,
      Medical Research Council Institute of Genetics &amp; Molecular Medicine, University
      of Edinburgh, Edinburgh, UK.
FAU - Tzoulaki, Ioanna
AU  - Tzoulaki I
AD  - Department of Epidemiology and Biostatistics, School of Public Health, Imperial
      College London, London, UK.
FAU - Tsilidis, Konstantinos K
AU  - Tsilidis KK
AD  - Department of Epidemiology and Biostatistics, School of Public Health, Imperial
      College London, London, UK.
AD  - Department of Hygiene and Epidemiology, University of Ioannina School of
      Medicine, Ioannina, Greece.
FAU - Ioannidis, P A
AU  - Ioannidis PA
AD  - Stanford Prevention Research Center, Stanford School of Medicine, Stanford, CA,
      USA.
AD  - Department of Health Research and Policy, Stanford School of Medicine, Stanford, 
      CA, USA.
AD  - Department of Statistics, Stanford University, Stanford, CA, USA.
FAU - Campbell, Harry
AU  - Campbell H
AD  - Centre for Global Health Research, Usher Institute of Population Health Sciences 
      and Informatics, University of Edinburgh, Edinburgh EH8 9AG, UK.
FAU - Theodoratou, Evropi
AU  - Theodoratou E
AD  - Centre for Global Health Research, Usher Institute of Population Health Sciences 
      and Informatics, University of Edinburgh, Edinburgh EH8 9AG, UK
      [email protected]
AD  - Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit,
      Medical Research Council Institute of Genetics &amp; Molecular Medicine, University
      of Edinburgh, Edinburgh, UK.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20170607
PL  - England
TA  - BMJ
JT  - BMJ (Clinical research ed.)
JID - 8900488
RN  - 0 (Biomarkers)
RN  - 268B43MJ25 (Uric Acid)
SB  - AIM
SB  - IM
MH  - Biomarkers/blood
MH  - Gout/*blood
MH  - Humans
MH  - Mendelian Randomization Analysis
MH  - Nephrolithiasis/*blood
MH  - Observational Studies as Topic
MH  - Randomized Controlled Trials as Topic
MH  - Uric Acid/*blood
PMC - PMC5461476
COI - Competing interests: All authors have completed the ICMJE uniform disclosure form
      at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding 
      author) and declare: no support from any organisation for the submitted work; no 
      financial relationships with any organisations that might have an interest in the
      submitted work in the previous three years; no other relationships or activities 
      that could appear to have influenced the submitted work.
EDAT- 2017/06/09 06:00
MHDA- 2017/06/20 06:00
CRDT- 2017/06/09 06:00
PST - epublish
SO  - BMJ. 2017 Jun 7;357:j2376. doi: 10.1136/bmj.j2376.

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