Gout flares a red flag for CV risk

Heart attacks and strokes are more likely in the first few months after a gout flare, research suggests.

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Doctors are being urged to watch out for signs of heart attack or stroke in patients who’ve recently had a gout flare, after new research shows patients are at a higher risk over the next month.

The study in JAMA analysed the rates of cardiovascular events in more than 90,000 UK patients newly diagnosed with gout. This database analysis of primary care, hospital and death data found that the odds of having a cardiovascular event almost doubled if the patient had had a flare in the two months prior.

Of the 90,000 patients with gout, around 10,000 had a cardiovascular event after their diagnosis. Myocardial infarction accounted for around half of the cardiovascular events, with ischemic and haemorrhagic stroke making up the other half.

The odds of a flare were 50% higher among patients who had a stroke or heart attack 61-120 days after, compared to those who did not have a cardiovascular event.

However, the risks of a cardiovascular event then appeared to decline, returning to baseline after four months.

“Patients with cardiovascular events had significantly increased odds of a gout flare during the preceding 120 days compared with patients who did not experience cardiovascular events,” the researchers wrote.

“These findings suggest that gout flares are associated with a transient increase in cardiovascular events following flares.”

Gout is associated with cardiovascular disease, but there has been little research into whether there is a temporal association between the two.

The authors noted gout flares were characterised by neutrophil-rich acute inflammation due to NLRP-3 inflammasome activation. And neutrophilic inflammation was associated with atherosclerotic plaque instability and rupture, they said.

“This may explain the association between cardiovascular events and recent prior gout flares,” they wrote in JAMA.

“Additionally, acute infection and surgery are associated with atrial fibrillation, and the same may be the case for gout flares, providing another potential mechanism.”

Perth rheumatologist Helen Keen said the study was consistent with the findings of her team’s similar cohort study presented at the American Cardiology Association conference last year.

“We looked at major adverse cardiac events: coronary death, stroke, acute coronary syndrome and heart failure,” said Professor Keen, adjunct associate professor in rheumatology at UWA.

“We found increased rates of all those in the 30 days post-admission with acute gout compared to before or after.

“This study makes sense from what we know about acute inflammation causing plaque destabilisation in the setting of the flu or respiratory diseases such as pneumonia.”

Professor Keen said the UK study was a reminder that gout was a chronic disease that needed to be addressed.

“It’s a call to remind us that gout is not an intermittent arthritis, it’s a chronic systemic disease that is often given less attention than diabetes, high blood pressure and high cholesterol.

“We can see that having an acute attack of gout, which occurs if people haven’t got their gout well controlled, can lead to bad cardiovascular outcomes.

“It does raise questions about how aggressively we need to manage acute attacks of gout.”

Professor Keen said the association between gout and cardiovascular disease was multifactorial and influenced by comorbidities.

“People with gout are often overweight with metabolic syndrome, are hypertensive and have high cholesterol. Then there’s the direct impact of having high uric acid, which is both pro and antioxidant on the blood vessels, which can be associated with cardiovascular events as well.

“There is the added impact of acute inflammatory episodes which cause plaque destabilisation.

“So while we think that controlling gout better will prevent cardiovascular deaths because of all those reasons, it’s been quite difficult to show that lowering uric acid translates to better cardiovascular outcomes.”

Gout was often not well managed, but that was a failure of the medical community, Professor Keen said. Even in tertiary hospitals that manage patients with acute gout, patients were often not managed according to internationally recognised guidelines, she said.

“There’s also a perception in the community and perhaps among patients that it’s not a severe systemic disease with consequences, but that it’s an intermittent arthritis that goes away in two days or a week and then they don’t need to do anything about it.”

In a smaller analysis of patients who had both a gout flare and a subsequent cardiovascular event, the JAMA authors found the risk was highest in the two months following the flare-up, and dropped over time.

Gout patients were almost twice as likely to have a cardiovascular event in the first two months, 64% more likely in the third and fourth months and 30% more likely in the six months after the flare, compared to those who had a flare more than six months after the cardiovascular event or five months before.

JAMA 2022, online 2 August