Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Association of plasma uric acid with ischaemic heart disease and blood pressure
T2 - mendelian randomisation analysis of two large cohorts
AU - Palmer, Tom M.
AU - Nordestgaard, Børge G.
AU - Benn, Marianne
AU - Tybjærg-Hansen, Anne
AU - Davey Smith, George
AU - Lawlor, Debbie A.
AU - Timpson, Nicholas J.
PY - 2013/7/18
Y1 - 2013/7/18
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Blood Pressure
KW - Body Mass Index
KW - Denmark
KW - Female
KW - Humans
KW - Hyperuricemia
KW - Male
KW - Mendelian Randomization Analysis
KW - Middle Aged
KW - Myocardial Ischemia
KW - Prospective Studies
KW - Regression Analysis
KW - Uric Acid
M3 - Journal article
C2 - 23869090
VL - 347
JO - BMJ
JF - BMJ
SN - 0959-8138
M1 - f4262
ER -