medwireNews: Gout flares are associated with an increased risk for cardiovascular (CV) events in the following 120 days, study findings suggest.
These findings “should alert clinicians and patients to the increased cardiovascular risk in the weeks beginning after a gout flare and should focus attention on optimizing preventive measures,” write the authors of a commentary accompanying the research published in JAMA.
The nested case-control study included 10,475 people with newly diagnosed gout and a subsequent CV event (acute myocardial infarction [MI] or stroke) and 52,099 matched individuals without CV events who were included in a UK primary care database between 1997 and 2020. In all, 44.9% of these people received medical care for a gout flare during a mean follow-up of 5.3 years from diagnosis.
Edoardo Cipolletta (Nottingham City Hospital, UK) and colleagues found that people with CV events were significantly more likely than those without to have had a gout flare in the preceding 60 days, with rates of 2.0% versus 1.4% and an odds ratio (OR) of 1.93 after adjustment for variables including CV risk factors and gout medication.
This association remained significant for gout flares in the previous 61–120 days, at rates of 1.6% in people with CV events and 1.2% in those without (adjusted OR=1.57). However, rates of gout flare in the previous 121–180 days were comparable in the two groups, at 1.4% and 1.3%, respectively.
Cipolletta et al then validated these results in a self-controlled case series involving 1421 patients with at least one gout flare and at least one CV event after gout diagnosis, which “accounted for residual between-person confounding and confirmed the results of the nested case-control study.”
In this analysis, rates of CV events per 1000 person–days were significantly higher in the 0–60 days and 61–120 days post-flare relative to the baseline period (180–31 days pre-flare and 181–540 days post-flare), at 2.49 and 2.16 versus 1.32, respectively. CV event rates were not significantly different at 121–180 days post-flare compared with the baseline period.
The authors of the accompanying commentary stress that “these associations cannot prove causality,” but they say that “[t]he consistent results of the case-control and self-controlled case studies provide additional confidence in the validity of the link between gout flares and temporally related MI and stroke.”
They say that the mechanism underlying this association “likely involves atherothrombosis,” and that the study results “reinforce the basic hypothesis that systemic inflammatory disease activity can facilitate vascular inflammation, which is now accepted as a key promoter of acute vascular events.”
Jeffrey Anderson and Kirk Knowlton, both from Intermountain Medical Center in Salt Lake City, Utah, USA, say that the increased CV risk following flares, despite use of colchicine or other standard gout treatment, suggests “an opportunity for additional therapies to reduce risk of cardiovascular events,” such as more potent interleukin (IL)-1 inhibitors than those in current use, and agents targeting IL-18.
Nevertheless, “[p]reventing gout flares with diet and uric acid lowering likely represents the most important therapeutic opportunity to reduce gout flares and their associated risk of cardiovascular events,” they conclude.
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