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@article{Gill:2021:10.1161/HYPERTENSIONAHA.120.16547,
author = {Gill, D and Cameron, AC and Burgess, S and Li, X and Doherty, DJ and Karhunen, V and Abdul-Rahim, AH and Taylor-Rowan, M and Zuber, V and Tsao, PS and Klarin, D and VA, Million Veteran Program and Evangelou, E and Elliott, P and Damrauer, SM and Quinn, TJ and Dehghan, A and Theodoratou, E and Dawson, J and Tzoulaki, I},
doi = {10.1161/HYPERTENSIONAHA.120.16547},
journal = {Hypertension},
pages = {383--392},
title = {Urate, blood pressure and cardiovascular disease: evidence from Mendelian randomization and meta-analysis of clinical trials},
url = {http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.16547},
volume = {77},
year = {2021}
}

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TY  - JOUR
AB  - Serum urate has been implicated in hypertension and cardiovascular disease, but it is not known whether it is exerting a causal effect. To investigate this, we performed Mendelian randomization analysis using data from UK Biobank, Million Veterans Program and genome-wide association study consortia, and meta-analysis of randomized controlled trials. The main Mendelian randomization analyses showed that every 1-SD increase in genetically predicted serum urate was associated with an increased risk of coronary heart disease (odds ratio, 1.19 [95% CI, 1.10–1.30]; P=4×10−5), peripheral artery disease (1.12 [95% CI, 1.03–1.21]; P=9×10−3), and stroke (1.11 [95% CI, 1.05–1.18]; P=2×10−4). In Mendelian randomization mediation analyses, elevated blood pressure was estimated to mediate approximately one-third of the effect of urate on cardiovascular disease risk. Systematic review and meta-analysis of randomized controlled trials showed a favorable effect of urate-lowering treatment on systolic blood pressure (mean difference, −2.55 mm Hg [95% CI, −4.06 to −1.05]; P=1×10−3) and major adverse cardiovascular events in those with previous cardiovascular disease (odds ratio, 0.40 [95% CI, 0.22–0.73]; P=3×10−3) but no significant effect on major adverse cardiovascular events in all individuals (odds ratio, 0.67 [95% CI, 0.44–1.03]; P=0.07). In summary, these Mendelian randomization and clinical trial data support an effect of higher serum urate on increasing blood pressure, which may mediate a consequent effect on cardiovascular disease risk. High-quality trials are necessary to provide definitive evidence on the specific clinical contexts where urate lowering may be of cardiovascular benefit.
AU  - Gill,D
AU  - Cameron,AC
AU  - Burgess,S
AU  - Li,X
AU  - Doherty,DJ
AU  - Karhunen,V
AU  - Abdul-Rahim,AH
AU  - Taylor-Rowan,M
AU  - Zuber,V
AU  - Tsao,PS
AU  - Klarin,D
AU  - VA,Million Veteran Program
AU  - Evangelou,E
AU  - Elliott,P
AU  - Damrauer,SM
AU  - Quinn,TJ
AU  - Dehghan,A
AU  - Theodoratou,E
AU  - Dawson,J
AU  - Tzoulaki,I
DO  - 10.1161/HYPERTENSIONAHA.120.16547
EP  - 392
PY  - 2021///
SN  - 0194-911X
SP  - 383
TI  - Urate, blood pressure and cardiovascular disease: evidence from Mendelian randomization and meta-analysis of clinical trials
T2  - Hypertension
UR  - http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.16547
UR  - http://hdl.handle.net/10044/1/85941
VL  - 77
ER  -

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