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Annual gout flare frequency as a marker of sustained cardiovascular risk: a clinical threshold for risk

Kuei-Ting Tung1, Solomon Chih-Cheng Chen2,3, Chun Lee4

  • 1Division of Nephrology, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City, Taiwan.

Rheumatology (Oxford, England)
|July 16, 2026
PubMed

Insights

Higher annual gout flare frequency predicts increased long-term cardiovascular risk. Moderate to high flares elevate heart failure risk, while high flare frequency is linked to atherothrombotic events like stroke and myocardial infarction.

Area of Science:

  • Rheumatology
  • Cardiology
  • Epidemiology

Background:

  • Gout is a chronic inflammatory condition associated with increased cardiovascular disease risk.
  • The cumulative inflammatory burden from gout flares may contribute to long-term cardiovascular events.
  • Understanding the relationship between gout flare frequency and major adverse cardiovascular events (MACEs) is crucial for risk stratification.

Purpose of the Study:

  • To investigate whether annual gout flare frequency predicts long-term MACEs.
  • To determine if higher gout flare frequency correlates with increased cardiovascular risk.
  • To assess the association between gout flare burden and specific cardiovascular outcomes.

Main Methods:

  • Utilized the TriNetX Global Collaborative Network to identify adult patients with a first treated gout flare in 2017.
  • Classified patients into low (≤3), moderate (4-6), or high (≥7) flares/year based on a 12-month exposure window.
  • Employed 1:1 propensity score matching to compare MACE risk (myocardial infarction, stroke, heart failure) and conducted a sensitivity analysis with a stricter flare definition.

Main Results:

  • A graded dose-response relationship was observed between flare frequency and MACE risk over 7 years.
  • High flare frequency (≥7/year) was associated with a 45% increased MACE risk (RR 1.45), and moderate frequency (4-6/year) with a 24% increase (RR 1.24) compared to low frequency.
  • Heart failure risk increased with both moderate and high flare frequencies, while stroke and myocardial infarction risks were elevated only in the high flare group.

Conclusions:

  • Annual gout flare frequency serves as a graded marker of sustained cardiovascular risk.
  • Moderate to high gout flare burden increases heart failure risk.
  • Atherothrombotic events like stroke and myocardial infarction are predominantly associated with high gout flare frequency, indicating a need for greater cumulative inflammatory exposure for these events.
Abstract

Keywords:
NLRP3 inflammasomegoutheart failurelandmark designmajor adverse cardiovascular events (MACE)urate-lowering therapy

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