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Background: Gout is associated with cardiovascular diseases, including tachyarrhythmia such as atrial fibrillation, atrial flutter, conduction system abnormalities, and supraventricular ventricular tachycardia [1,2]. Activation of the NALP-3 inflammasome is implicated in arrhythmogenesis [3]. As gout flares are driven by activation of the same pathway, we hypothesised that there would be a transient increase in the risk of tachyarrhythmia immediately after a gout flare.
Objectives: To investigate whether a recent gout flare is associated with a transient increased risk of tachyarrhythmia.
Methods: Two studies of patients with newly diagnosed gout were conducted in England and Sweden using primary care, hospitalisation and mortality records. Nested case-control studies of new tachyarrhythmia diagnosis (i.e., a composite of atrial fibrillation/flutter, other supraventricular tachycardia or ventricular tachyarrhythmia as the primary outcome) were performed. Self-controlled case series analyses were carried out in a subpopulation with gout flare and tachyarrhythmia. Secondary outcomes were the individual components of the primary outcome. Gout flare was the exposure of interest. We included cataract as a negative control outcome and earwax impaction as a negative control exposure. The strength of the association was measured using adjusted odds ratios (aORs) with 95% confidence intervals (95%CIs) in nested case-control studies and adjusted incidence rate ratios (aIRRs) with 95%CIs in self-controlled case series.
Results: 20,157 and 1,995 patients with a new diagnosis of tachyarrhythmia (cases) were matched by age, sex, and gout duration with 76,835 and 6,086 patients without tachyarrhythmia (controls) in England and Sweden, respectively. In both countries, the mean (standard deviation) age of cases was 76.0 (11.0) years, 31.5% were female, and the median duration of gout was 3.5 years. Cases with tachyarrhythmia, compared with controls, had significantly higher odds of gout flare within the prior 0 to 30 days (aOR: 1.41, 95%CI: 1.07-1.85 in England; 1.71, 95%CI: 1.10-2.65 in Sweden) but not within the prior 31-120 days, compared to no or remote (>120 days prior) flares in multivariable analysis (Table 1). In self-controlled case series analyses (N=2,893 in England and N=150 in Sweden), the aIRRs of tachyarrhythmia were 1.44 (95%CI: 1.26-1.64) and 4.15 (95%CI: 2.47-6.97), respectively, in the 0-30 days after a gout flare compared with the baseline period (Table 2).
No significant associations were observed with the negative control outcome or exposure
Conclusions: Gout flares are associated with a transient increase in the risk of tachyarrhythmia.
Association Between Incident Tachyarrhythmia and Recent Prior Gout Flare in a Nested Case-Control Study in a fully adjusted multivariable model.
| Gout flare exposure window, days | Adjusted OR (95%CI) |
|---|---|
| Main analysis | |
| CPRD Aurum [N=96,992] | |
| 0-30 | 1.41 (1.07 to 1.85) |
| 31-60 | 1.05 (0.79 to 1.38) |
| 61-90 | 1.22 (0.92 to 1.62) |
| 91-120 | 1.09 (0.81 to 1.46) |
| >120 or no flares | 1 [Reference] |
| VEGA [N=8,081] | |
| 0-30 | 1.71 (1.10 to 2.65) |
| 31-60 | 0.62 (0.33 to 1.18) |
| 61-90 | 0.91 (0.48 to 1.72) |
| 91-120 | 1.12 (0.61 to 2.04) |
| >120 or no flares | 1 [Reference] |
| Atrial fibrillation/flutter | |
| CPRD Aurum [N=85,900] | |
| 0-30 | 1.35 (1.01 to 1.81) |
| 31-60 | 1.06 (0.79 to 1.42) |
| 61-90 | 1.16 (0.86 to 1.58) |
| 91-120 | 1.05 (0.77 to 1.45) |
| >120 or no flares | 1 [Reference] |
| VEGA [N=4,688] | |
| 0-30 | 1.92 (1.11 to 3.30) |
| 31-60 | 0.53 (0.34 to 0.94) |
| 61-90 | 0.67 (0.31 to 1.45) |
| 91-120 | 0.79 (0.41 to 1.55) |
| >120 or no flares | 1 [Reference] |
| Supraventricular tachycardia | |
| CPRD Aurum [N=3,530] | |
| 0-30 | 1.28 (0.30 to 5.51) |
| 31-60 | 0.67 (0.13 to 3.47) |
| 61-90 | 2.99 (0.70 to 12.81) |
| 91-120 | 1.01 (0.17 to 6.01) |
| >120 or no flares | 1 [Reference] |
| Ventricular tachyarrhythmia | |
| CPRD Aurum [N=7,562] | |
| 0-30 | 1.93 (0.69 to 5.39) |
| 31-60 | 0.99 (0.29 to 3.34) |
| 61-90 | 1.59 (0.60 to 4.23) |
| 91-120 | 1.53 (0.63 to 3.73) |
| >120 or no flares | 1 [Reference] |
Results of the Self-controlled Case Series Analysis for Patients with a First Episode of Gout and Tachyarrhythmia.
| Gout flare exposure window | Adjusted incidence rate ratio (95%CI) |
|---|---|
| Main analysis | |
| CPRD Aurum [N=2,893] | |
| Flare date to 30d after flare | 1.44 (1.26 to 1.64) |
| 31-60d after flare | 1.34 (1.17 to 1.54) |
| 61-90d after flare | 1.16 (1.0 to 1.34) |
| 91-120d after flare | 1.06 (0.90 to 1.24) |
| Baseline period a | Reference |
| VEGA [N=150] | |
| Flare date to 30d after flare | 4.15 (2.47 to 6.97) |
| 31-60d after flare | 2.25 (1.13 to 4.48) |
| 61-90d after flare | 0.75 (0.24 to 2.37) |
| 91-120d after flare | 1.70 (0.79 to 3.70) |
| Baseline period a | Reference |
| Considering atrial fibrillation/flutter as the outcome | |
| CPRD Aurum [N=2,534] | |
| Flare date to 30d after flare | 1.39 (1.20 to 1.60) |
| 31-60d after flare | 1.33 (1.14 to 1.54) |
| 61-90d after flare | 1.07 (0.91 to 1.27) |
| 91-120d after flare | 1.02 (0.86 to 1.21) |
| Baseline period a | Reference |
| VEGA [N=126] | |
| Flare date to 30d after flare | 4.46 (2.60 to 7.65) |
| 31-60d after flare | 1.40 (0.56 to 3.46) |
| 61-90d after flare | 0.56 (0.14 to 2.27) |
| 91-120d after flare | 1.36 (0.55 to 3.39) |
| Baseline period a | Reference |
| Considering other supraventricular tachycardia as the outcome | |
| CPRD Aurum [N=134] | |
| Flare date to 30d after flare | 1.59 (0.86 to 2.94) |
| 31-60d after flare | 1.49 (0.79 to 2.82) |
| 61-90d after flare | 2.17 (1.25 to 3.75) |
| 91-120d after flare | 1.07 (0.51 to 2.23) |
| Baseline period a | Reference |
| Considering ventricular tachyarrhythmia as the outcome | |
| CPRD Aurum [N=225] | |
| Flare date to 30d after flare | 2.11 (1.39 to 3.20) |
| 31-60d after flare | 1.48 (0.90 to 2.44) |
| 61-90d after flare | 1.52 (0.92 to 2.52) |
| 91-120d after flare | 1.50 (0.89 to 2.50) |
| Baseline period a | Reference |
| Analyses were adjusted for age and calendar season. a Baseline period indicates 365 to 1 days before the flare, plus 121 to 365 days after the flare. | |
REFERENCES: [1] Kim SC, et al. Ann Rheum Dis. 2016;75:1473–8.
[2] Ferguson LD, et al. Lancet Rheumatol. 2024;6:e156–67.
[3] Yao C, et al. Circulation. 2018;138:2227–42.
Acknowledgments: NIL.
Disclosure of Interests: Edoardo Cipolletta IBSA and Novartis, Horizon Therapeutics, Tatiana Zverkova Sandström: None declared, Georgina Nakafero: None declared, Davide Rozza: None declared, Panagiota Drivelegka: None declared, Gianluca Moroncini: None declared, Anthony Avery: None declared, Laila Tata: None declared, Mamas Mamas: None declared, Mats Dehlin: None declared, Abhishek Abhishek: None declared.