Details

Autor(en) / Beteiligte

• 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

Titel

Urate, Blood Pressure, and Cardiovascular Disease: Evidence From Mendelian Randomization and Meta-Analysis of Clinical Trials

Ist Teil von

• Hypertension (Dallas, Tex. 1979), 2021-02, Vol.77 (2), p.383-392

Ort / Verlag

United States: Lippincott Williams & Wilkins

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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]; =4×10 ), peripheral artery disease (1.12 [95% CI, 1.03-1.21]; =9×10 ), and stroke (1.11 [95% CI, 1.05-1.18]; =2×10 ). 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]; =1×10 ) and major adverse cardiovascular events in those with previous cardiovascular disease (odds ratio, 0.40 [95% CI, 0.22-0.73]; =3×10 ) but no significant effect on major adverse cardiovascular events in all individuals (odds ratio, 0.67 [95% CI, 0.44-1.03]; =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.