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Urate-lowering therapy in cardiovascular pharmacotherapy: from Mendelian randomization data to cardio-renal-metabolic

Claudio Borghi1, Federica Fogacci1,2, Arrigo F G Cicero1,3

  • 1Hypertension and Cardiovascular Risk Research Center, Medical and Surgical Sciences Department, Alma Mater Studiorum University of Bologna, Via Massarenti 9, Bologna 40138, Italy.

European Heart Journal. Cardiovascular Pharmacotherapy
|June 17, 2026
PubMed

Insights

Serum uric acid (SUA) is linked to cardiovascular risk, but urate-lowering therapy (ULT) isn't proven for preventing cardiovascular events in asymptomatic hyperuricemia. Focus ULT on gout and symptomatic cases.

Area of Science:

  • Cardiology
  • Nephrology
  • Metabolic Syndrome

Background:

  • Serum uric acid (SUA) and hyperuricemia are increasingly recognized as cardiovascular (CV) risk factors beyond gout.
  • Hyperuricemia often coexists with obesity, hypertension, diabetes, and chronic kidney disease (CKD).

Purpose of the Study:

  • To review epidemiological, Mendelian randomization (MR), and pharmacological evidence on SUA and urate-lowering therapy (ULT) in cardiovascular pharmacotherapy.
  • To define the role of SUA and ULT in managing cardiovascular risk.

Main Methods:

  • Synthesis of population-based studies, MR analyses, and randomized trials of various urate-lowering drugs (e.g., xanthine oxidase inhibitors, uricosurics, uricases).
  • Analysis of drug-target MR and cardiovascular drugs with urate-modifying effects.
  • Inclusion of large trials and real-world cohorts evaluating ULT in specific cardiovascular conditions.

Main Results:

  • Higher SUA correlates with increased risk of coronary artery disease, heart failure, stroke, cardio-renal-metabolic syndromes, and mortality.
  • MR studies suggest a causal link between genetically elevated SUA and blood pressure, coronary disease, and advanced CKD.
  • Large trials show no consistent CV event reduction with ULT in asymptomatic hyperuricemia or stable cardiovascular disease; however, observational data hint at potential benefits with specific ULT regimens.

Conclusions:

  • Serum uric acid is a cardio-renal-metabolic biomarker and a potential therapeutic target in specific patient phenotypes.
  • Current evidence does not support routine ULT for CV prevention in asymptomatic hyperuricemia.
  • ULT should primarily target gout and symptomatic hyperuricemia, employing phenotype-guided strategies for patient selection.
Abstract

Keywords:
Cardiovascular diseaseMendelian randomizationSerum uric acidUrate-lowering therapy

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