Background/Purpose:
Atrial fibrillation
(AF) is the most common arrhythmia associated with cardiovascular disease and
mortality. There are increasing data supporting the role of inflammation in the
development and maintenance of AF. Recent observational studies report an
increased risk of sinus tachycardia, AF and left atrial thrombus in patients
with hyperuricemia, but little is known whether gout is associated with the
risk of AF.

Methods: Using data from a US commercial
insurance plan (2004-2013), we conducted a cohort study to evaluate the
incidence rate (IR) of AF in patients with gout compared to osteoarthritis (OA).
Patients with gout or OA were identified with ≥2 diagnosis codes and
≥1 dispensing for a gout- or OA-related drug. The index date was defined
as the date of the first dispensing of a gout or OA-related drug (i.e. NSAIDs,
opioids) after ≥365-days continuous enrollment. We excluded patients with a diagnosis of arrhythmia or cardiac
surgery, or who used anti-arrhythmics or anticoagulants in the 365-day
period prior to the index date. The OA group was then matched to the gout group
on age, sex and the index date with a 3:1 ratio. Incident AF was defined as a
new AF diagnosis and a dispensing for a new anticoagulant or
anti-arrhythmic. Baseline ESR, CRP and serum uric acid levels were available on
a subgroup of patients. We calculated the incidence rates (IR) of AF and confidence
intervals (CI) in both groups. Multivariable Cox proportional hazards models
compared the risk of AF in gout versus OA.  

Results:
We identified 70,015 patients
with gout and 210,045 with OA, matched on age, sex, and the index date. The
mean age was 57 years and 81% were men. Among patients with baseline ESR,CRP or
uric acid levels available, 35.5% of gout and 23.4% of OA patients had elevated
ESR or CRP levels and the mean (SD) uric acid level (in mg/dL) was 7.4 (2.0) in
gout and 5.9 (1.4) in OA. Over the mean 2-year follow-up, the IR of AF per
1,000 person-years was 7.19 in gout and 5.87 in OA. The age and sex-adjusted HR
of AF was 1.23 (95%CI 1.14-1.32) in gout versus OA. In the multivariable Cox
regression adjusted for age, sex, comorbidities, medications and healthcare
utilization, the HR of AF in gout was 1.13 (95%CI 1.04-1.23).  In the subgroup
analyses, the HR of AF in gout was 1.22 (95%CI 0.81-1.84) further adjusted for
elevated ESR/CRP and 1.57 (95%CI 1.04-2.36) further adjusted for serum uric
acid levels.

Conclusion:
In this large
population-based cohort study, gout was associated with a modestly increased
risk of incident AF versus OA. It may be important to examine the role of gout
treatment such as xanthine oxidase inhibitors and colchicine in the primary or
secondary prevention of AF in patients with gout.