Keele Research Repository

Importance Gout is associated with cardiovascular diseases. The temporal association between gout flares and cardiovascular events has not been investigated. Objective To investigate whether there is a transient increase in risk of cardiovascular events after a recent gout flare. Design, setting and participants A retrospective observational study was conducted using electronic health records from the Clinical Practice Research Datalink in England between January 1, 1997, and December 31, 2020. A multivariable nested case-control study, and self-controlled case series adjusted for season and age were performed among 62574 patients with gout, and 1421 patients with gout flare and cardiovascular event, respectively. Exposures Gout flares were ascertained using hospitalization, primary-care outpatient consultation and prescription records. Main Outcomes and Measures The primary outcome was a cardiovascular event, defined as an acute myocardial infarction or stroke. Association with recent prior gout flares was measured using adjusted odds ratios (aOR) and adjusted incidence rate ratios (aIRR) with 95% confidence intervals (95%CI) in a nested case-control study and a self-controlled case series, respectively. Results Among patients with a new diagnosis of gout (mean age 76.5 years, 69.3% men), 10475 patients with subsequent cardiovascular events were matched to 52099 patients without cardiovascular events. Patients with cardiovascular events, compared to those without cardiovascular events, had significantly higher odds of gout flare within the prior 0-60 days (204/10475 (2.0%) vs 743/52099 (1.4%); aOR, 1.93 (95%CI, 1.57-2.38)) and 61-120 days (170/10475 (1.6%) vs 628/52099 (1.2%); aOR, 1.57 (95%CI, 1.26-1.96). There was no significant difference in the odds of gout flare within prior 121-180 days (148/10475 (1.4%) vs 662/52099 (1.3%); aOR, 1.06 (95%CI, 0.84-1.34)). In the self-controlled case series (N=1421), cardiovascular event rates (95%CI) were 2.49 (2.16-2.82); 2.16 (1.85-2.47); 1.70 (1.42-1.98)/1000 person-days during 0-60, 61-120, 121-180 days after gout flare compared to 1.32 (1.23-1.41)/1000 person-days during the 180 days before and 181-540 days after the gout flare. Compared with 180 days before and 181-540 days after a gout flare, incidence rate differences (95%CI) and aIRRs (95%CI) for cardiovascular events were 1.17 (0.83-1.52), 0.84 (0.52-1.17), 0.38 (0.09-0.67)/1000 person-days, and 1.89 (1.54-2.30); 1.64 (1.45-1.86); 1.29 (1.02-1.64) within 0-60, 61-120, and 121-180 days after a gout flare, respectively. Conclusions and Relevance Among individuals with gout, those who experienced a cardiovascular event, compared with those who did not experience such an event, had significantly higher odds of a recent gout flare in the preceding days. These findings suggest gout flares are associated with a transient increase in cardiovascular events following the flare.