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Serum uric acid levels as a causal factor in hypertension: Insights from Mendelian randomization analysis

Jiayue Xu1, Jiajing Zhao2, Jiaming Gu3

  • 1Department of Traditional Chinese Medicine, Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital, Shanghai, China.

Clinical and Experimental Hypertension (New York, N.Y. : 1993)
|May 6, 2025
PubMed

Insights

High serum uric acid (SUA) levels causally increase hypertension risk. This Mendelian randomization study confirms a one-way link, highlighting SUA management for blood pressure control.

Area of Science:

  • Genetics
  • Epidemiology
  • Cardiovascular Disease

Background:

  • Hyperuricemia and hypertension are common, often co-occurring chronic diseases.
  • Observational studies suggest a link between serum uric acid (SUA) and hypertension, but causality is unclear due to confounding factors.
  • This study uses Mendelian randomization (MR) to investigate the causal relationship between SUA levels and hypertension risk.

Purpose of the Study:

  • To determine if elevated serum uric acid (SUA) levels causally influence the risk of developing hypertension.
  • To differentiate the direction of causality between SUA and blood pressure using genetic variants.
  • To provide robust evidence mitigating confounding and reverse causation inherent in observational studies.

Main Methods:

  • Employed Mendelian randomization (MR) using single nucleotide polymorphisms (SNPs) as genetic instruments for serum uric acid (SUA) levels.
  • Utilized a two-sample MR design with GWAS data from European populations.
  • Assessed systolic and diastolic blood pressure as outcomes, with sensitivity analyses including weighted median and MR-Egger.

Main Results:

  • Genetically predicted higher SUA levels showed a significant positive causal association with increased systolic blood pressure (SBP) and diastolic blood pressure (DBP).
  • Reverse MR analysis indicated no significant causal effect of SBP or DBP on SUA levels, confirming a unidirectional relationship.
  • Findings suggest a causal link where elevated SUA contributes to hypertension development.

Conclusions:

  • This MR study provides strong evidence for a unidirectional causal relationship between higher SUA levels and an increased risk of hypertension.
  • The findings underscore the clinical significance of managing SUA levels to reduce hypertension risk.
  • Further research, including RCTs, is warranted to confirm these results and explore SUA-targeted interventions.
Abstract

Keywords:
Mendelian randomizationSerum uric acidcausal relationshipgenetic epidemiologyhypertension risk

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