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

OBJECTIVES: We examined whether annual gout flare frequency, as a marker of cumulative inflammatory burden, predicts long-term major adverse cardiovascular events (MACE). METHODS: Using the TriNetX Global Collaborative Network, we identified adults with a first EHR-recorded treated gout flare in 2017. Using a 12-month landmark exposure window, patients were classified as low (≤3), moderate (4-6), or high (≥7) flares/year. Modified MACE (myocardial infarction, stroke, heart failure) was followed from the landmark. Groups were compared using 1:1 propensity score matching. A sensitivity analysis applied a stricter flare definition (gout diagnosis with colchicine, corticosteroid, or intra-articular injection within 0-3 days; NSAIDs excluded). RESULTS: Among 44,705 patients, matching produced balanced cohorts (high vs low, 13,179 pairs; moderate vs low, 9,700 pairs). A graded dose-response was observed: at 7 years, MACE risk was higher in the high (RR 1.45; 95% CI 1.37-1.53) and moderate (RR 1.24; 1.15-1.33) groups versus low. Heart failure risk was elevated in both groups (HR 1.27 [high]; 1.17 [moderate]); stroke and myocardial infarction were elevated only in the high group (7-year HR 1.28 each), with stroke significant from 3 years. Findings were consistent under the stricter sensitivity definition (7-year MACE HR 1.19 [high] and 1.12 [moderate]; Supplementary Figure S1). CONCLUSION: Annual gout flare frequency is a graded marker of sustained cardiovascular risk. Heart failure risk rises with both moderate and high burden, whereas atherothrombotic events emerge predominantly with high flare frequency, suggesting they require greater cumulative inflammatory exposure.