Gout Flare? Watch Out for Cardiovascular Events

As if gout flares aren’t bad enough by themselves, they come with increased risk for myocardial infarction (MI) and stroke over the next 2 months, researchers reported.

Among British gout patients, the incidence rate ratio for these cardiovascular events was 1.89 (95% CI 1.54-2.30) during the 60 days after a gout flare, after adjustment for covariates and relative to periods of at least 6 months prior to the flare, according to Edoardo Cipolletta, MD, of the University of Nottingham in England, and colleagues.

Event rates remained elevated, though to a small degree, through 6 months from a flare (adjusted IRR 1.29, 95% CI 1.02-1.64, for days 121-180 post-flare), they reported in JAMA.

Study limitations included the use of data that were extracted retrospectively from a prospective database, and the fact that the results showed association but not causation, the researchers noted.

Still, the findings were highly plausible and a call to action for gout patients’ doctors, stated Jeffrey L. Anderson, MD, and Kirk U. Knowlton, MD, both of Intermountain Medical Center in Salt Lake City, in an accompanying editorial.

“Clinicians should emphasize the importance of optimizing lifestyle measures and standard risk factor control, including adherence to diet, statins, anti-inflammatory drugs (e.g., aspirin, colchicine), smoking cessation, diabetic and blood pressure control, and antithrombotic medications as indicated,” they wrote.

Anderson and Knowlton also suggested that better control of gout pathology might be the best approach. “Preventing 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 concluded.

Cipolletta and colleagues drew on records from Britain’s Clinical Practice Research Datalink system, which captures data on patients treated in the country’s National Health Service. They identified 10,475 gout patients who had experienced strokes or MIs after their initial diagnosis, matching them by age, sex, BMI, gout duration, and other parameters with 52,099 gout patients without such events.

Mean patient age was about 77 and 70% were men. Importantly, about 52% among both cases and controls had never received urate-lowering therapy, and less than 20% were currently on it when records were examined.

“Patients with cardiovascular events, compared with those who did not have cardiovascular events, had significantly higher odds of gout flare within the prior 0 to 60 days,” the group reported, with an OR 1.93 after adjustments (95% CI 1.57-2.38). Actual flare incidence rates were 2.0% for those experiencing cardiovascular events versus 1.4% for those without.

Cipolletta and colleagues then performed another set of analyses on 1,421 patients who experienced gout flares plus at least one MI or stroke, comparing periods after the flare to those before. In the 60 days following a flare, these patients experienced events at a rate of 2.49 per 1,000 person-days, versus 1.32 per 1,000 person-days during periods before the flare.

The researchers noted that gout flares are accompanied by upticks in inflammatory markers, particularly those associated with neutrophils, which are also “associated with atherosclerotic plaque instability and rupture,” they wrote.

“This may explain the association between cardiovascular events and recent prior gout flares. Additionally, acute infection and surgery are associated with atrial fibrillation, and the same may be the case for gout flares, providing another potential mechanism,” the group added.