Association between tachyarrhythmia and gout flare in people with gout in England and Sweden: nested case–control studies and self-controlled case-series analyses

Summary Background Gout is associated with cardiovascular diseases including tachyarrhythmia; however, the mechanism underlying this association is unclear. We aimed to investigate whether a new diagnosis of tachyarrhythmia is associated with a gout flare in the previous 120 days. Methods Nested case–control and self-controlled case-series analyses were conducted in England and Sweden using primary care data from the Clinical Practice Research Datalink (CPRD; Jan 1, 2007, to March 29, 2021) and the Western Sweden Regional Healthcare Registry (VEGA; Jan 1, 2007, to Dec 31, 2017). The source population included people aged 18 years or older who contributed data to CPRD or VEGA, with linkage to secondary care and mortality records, and were newly diagnosed with gout during the study period. People with a diagnosis of tachyarrhythmia before gout diagnosis were excluded. For the nested case–control studies, cases (defined as patients with newly diagnosed tachyarrhythmia) and controls (defined as those without a diagnosis of tachyarrhythmia) were matched by age, sex, and gout duration with up to four controls. Self-controlled case-series analyses were performed in this cohort in people newly diagnosed with tachyarrhythmia within a year before or after the first gout flare. The main outcome was a new diagnosis of tachyarrhythmia. Gout flare was the exposure. Associations were evaluated using multivariable conditional logistic regression and adjusted odds ratios (aORs) with 95% CIs in nested case–control studies and adjusted incidence rate ratios (aIRRs) with 95% CIs in self-controlled case-series. Findings Among 260 254 eligible patients with newly diagnosed gout, 20 157 patients with a new diagnosis of tachyarrhythmia (cases) were matched with 76 835 patients without tachyarrhythmia (controls) in the English cohort. Among 19 346 eligible patients with gout, 1995 cases were matched with 6086 controls in the Swedish cohort. For the matched English cohort, the mean age was 76·3 years (SD 11·1), 30 182 (31·1%) of 96 992 were female, and 66 810 (68·9%) of 96 992 were male. For the matched Swedish cohort, the mean age was 76·3 years (SD 11·0), 2547 (31·5%) of 8081 were female, and 5534 (68·5%) of 8081 were male. The mean follow-up between gout diagnosis and the index date was 4·1 years (SD 3·1) in the English cohort and 2·5 years (2·1) in the Swedish cohort. Compared with controls, cases had significantly higher odds of gout flare within the previous 0–30 days (aOR 1·41 [95% CI 1·07–1·85] for England; 1·71 [1·10–2·65] for Sweden), but there was no significant difference in the odds of gout flare within the previous 31–120 days, compared with no or remote (>120 days previously) flares. In self-controlled case series analyses (2893 participants in the English cohort and 150 participants in the Swedish cohort), the aIRR of tachyarrhythmia compared with the baseline period was 1·44 (95% CI 1·26–1·64) 0–30 days after a gout flare and 1·34 (1·17–1·54) 31–60 days after a gout flare in the English cohort and 4·15 (2·47–6·97) 0–30 days after a gout flare and 2·25 (1·13–4·48) 31–60 days after a gout flare in the Swedish cohort; no differences were seen for the other intervals versus baseline. Interpretation Gout flares are associated with a transient increase in the risk of tachyarrhythmia. Patients presenting with a gout flare warrant increased cardiovascular vigilance over the next 30–60 days. Funding Foundation for Research in Rheumatology, University of Nottingham, and Reumatikerförbundet.