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Association of plasma uric acid with ischaemic heart disease and blood pressure: mendelian randomisation analysis of two large cohorts
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Palmer, Tom M., Nordestgaard, Børge G., Benn, Marianne, Tybjærg-Hansen, Anne, Smith, George Davey, Lawlor, Debbie A. and Timpson, Nicholas J. (2013) Association of plasma uric acid with ischaemic heart disease and blood pressure: mendelian randomisation analysis of two large cohorts. BMJ, Volume 347 . Article number f4262. doi:10.1136/bmj.f4262 ISSN 0959-535X.
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Official URL: http://dx.doi.org/10.1136/bmj.f4262
Abstract
Objectives: To assess the associations between both uric acid levels and hyperuricaemia, with ischaemic heart disease and blood pressure, and to explore the potentially confounding role of body mass index.
Design: Mendelian randomisation analysis, using variation at specific genes (SLC2A9 (rs7442295) as an instrument for uric acid; and FTO (rs9939609), MC4R (rs17782313), and TMEM18 (rs6548238) for body mass index).
Setting: Two large, prospective cohort studies in Denmark.
Participants: We measured levels of uric acid and related covariables in 58 072 participants from the Copenhagen General Population Study and 10 602 from the Copenhagen City Heart Study, comprising 4890 and 2282 cases of ischaemic heart disease, respectively.
Main outcome: Blood pressure and prospectively assessed ischaemic heart disease.
Results: Estimates confirmed known observational associations between plasma uric acid and hyperuricaemia with risk of ischaemic heart disease and diastolic and systolic blood pressure. However, when using genotypic instruments for uric acid and hyperuricaemia, we saw no evidence for causal associations between uric acid, ischaemic heart disease, and blood pressure. We used genetic instruments to investigate body mass index as a potentially confounding factor in observational associations, and saw a causal effect on uric acid levels. Every four unit increase of body mass index saw a rise in uric acid of 0.03 mmol/L (95% confidence interval 0.02 to 0.04), and an increase in risk of hyperuricaemia of 7.5% (3.9% to 11.1%).
Conclusion: By contrast with observational findings, there is no strong evidence for causal associations between uric acid and ischaemic heart disease or blood pressure. However, evidence supports a causal effect between body mass index and uric acid level and hyperuricaemia. This finding strongly suggests body mass index as a confounder in observational associations, and suggests a role for elevated body mass index or obesity in the development of uric acid related conditions.
Item Type: | Journal Article | ||||
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Subjects: | R Medicine > R Medicine (General) R Medicine > RA Public aspects of medicine |
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Library of Congress Subject Headings (LCSH): | Coronary heart disease, Hypertension, Uric acid, Clinical trials , Mendel's law, Genetics | ||||
Journal or Publication Title: | BMJ | ||||
Publisher: | BMJ Publishing Group Ltd. | ||||
ISSN: | 0959-535X | ||||
Official Date: | 18 July 2013 | ||||
Dates: |
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Volume: | Volume 347 | ||||
Page Range: | Article number f4262 | ||||
DOI: | 10.1136/bmj.f4262 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Open Access (Creative Commons) | ||||
Date of first compliant deposit: | 25 December 2015 | ||||
Date of first compliant Open Access: | 25 December 2015 | ||||
Funder: | Medical Research Council (Great Britain) (MRC), Hjerteforeningen [Danish Heart Foundation], Statens lægevidenskabelige forskningsråd (Denmark) [Danish Medical Research Council] (SLF), Copenhagen County Foundation, Herlev Hospital [Denmark], Rigshospitalet (Copenhagen, Denmark) | ||||
Grant number: | G0601625 (MRC) |
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