Urate, Blood Pressure, and Cardiovascular Disease: Evidence From Mendelian Randomization and Meta-Analysis of Clinical Trials. Issue 2 (February 2021)

• Record Type: Journal Article
• Authors: Gill, Dipender; Cameron, Alan C.; Burgess, Stephen; Li, Xue; Doherty, Daniel J.; Karhunen, Ville; Abdul-Rahim, Azmil H.; Taylor-Rowan, Martin; Zuber, Verena; Tsao, Philip S.; Klarin, Derek; Evangelou, Evangelos; Elliott, Paul; Damrauer, Scott M.; Quinn, Terence J.; Dehghan, Abbas; Theodoratou, Evropi; Dawson, Jesse; Tzoulaki, Ioanna
• Is Part Of: Hypertension. Volume 77:Issue 2(2021)
• Publication Date: 2021-02
• Subjects: blood pressure -- cardiovascular diseases -- odds ratio -- systematic review -- uric acid; Hypertension -- Periodicals; Hypertension -- Treatment -- Periodicals; 616.132005
• DOI: 10.1161/HYPERTENSIONAHA.120.16547
• Languages: English
• ISSNs: 0194-911X

Abstract

Abstract : 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. Abstract : Supplemental Digital Content is available in the text.