| Title: | Urate, Blood Pressure, and Cardiovascular Disease |
| Journal: | Hypertension |
| Published: | 28 Dec 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33356394/ |
| DOI: | https://doi.org/10.1161/hypertensionaha.120.16547 |
| URL: | https://www.ahajournals.org/doi/pdf/10.1161/HYPERTENSIONAHA.120.16547 |
Publication 9319
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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.</p>
20 Authors
- Dipender Gill
- Alan C. Cameron
- Stephen Burgess
- Xue Li
- Daniel J. Doherty
- Ville Karhunen
- Azmil H. Abdul-Rahim
- Martin Taylor-Rowan
- Verena Zuber
- Philip S. Tsao
- Derek Klarin
- VA Million Veteran Program
- Evangelos Evangelou
- Paul Elliott
- Scott M. Damrauer
- Terence J. Quinn
- Abbas Dehghan
- Evropi Theodoratou
- Jesse Dawson
- Ioanna Tzoulaki
1 Application
| Application ID | Title |
|---|---|
| 236 | Genome-wide association study of blood pressure. |
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