Gout & Mortality

Hi, this is Mark Fischer. I'm a rheumatologist in southeast Massachusetts and I'm here to talk to you about gout and mortality. So, as you all might guess, gout is associated with increased mortality. It is more than just episodic joint inflammation. And it's associated with a 20 to 25% increase in all cause mortality.

A 2023 meta-analysis by Shu Yun Wang and others with 11 cohort studies covering 2010 to 2022 and including 14.8 million patients with follow-up of up to 16 years showed a 23% increase in mortality. Cardiovascular mortality was increased by 29%. Infectious disease mortality by 24% and digestive disease mortality by 42%.

More striking, but not necessarily surprising, renal disease mortality was increased by 78% as shown by Dr. Vargas Santos and others using a Swedish registry. More surprising, however, Dr.Evelt and colleagues evaluated a cohort of 573 gout patients and found that the standardized mortality ratio for cancer was an incredible 3.58.

There are a number of risk factors associated with gout and mortality including tophaceous disease, a high uric acid of 9.4 or greater, coexisting chronic kidney disease, history of myocardial infarction, and history of heart failure. Dr. Lee and colleagues using the Korean National Health Insurance Service database showed that the combination of gout, CKD, and type 2 diabetes confers the highest risk with the impact being synergistic and not just additive.

And the bad news is we are not getting better at this. A study from the Han Cho group using a UK-based population study compared two time periods 1999 to 2006 and 2007 to 2014 and found an adjusted mortality hazard ratio of about 24%. And that did not improve. This is in marked contrast to rheumatoid arthritis which did see a reduction in mortality doing a similar comparison with the same data set.

The United States data is very similar. Another study by Natalie McCormack and the Han Cho group also showed no improvement over time with mortality hazard ratios of about 1.19 to 1.2. And this is after adjusting for serum uric acid and cardiovascular disease risk factors.

A little bit more insight into the cardiovascular piece of this. A case control study of gout patients by Dr. Perez-Ruiz and colleagues with over 62,000 patients compared those who had a cardiovascular event defined as MI or stroke with gout patients who did not have a cardiovascular event. And for those who did, they were 93% more likely to have had a gout flare in the 60 days before the event and 57% more likely from 61 to 120 days before the event. There was no difference after 120 days. And this suggests that gout flares are associated with an increased risk of cardiovascular events for up to 120 days following the flare.

Is there any good news? Well, there is some. First, gout was associated with a decreased risk of dementia related mortality as shown by Dr. Vargas Santos. And second, treating gout effectively may make a difference. Some observational studies did not show an improvement in mortality, but Dr. Cipolletta and colleagues showed that using a treat-to-target approach could lower the risk of cardiovascular events. Achieving a serum uric acid less than six increases survival at 5 years by 1%, and reaching uric acid below 6.0 could reduce the risk of cardiovascular events by 9%. Achieving a uric acid level below five reduces the risk of cardiovascular events by 23%.

Further, colchicine may be beneficial. Dan Solomon and colleagues using an EMR database linked with Medicare claims found colchicine use was associated with a 49% reduction in cardiovascular events and an incredible 73% reduction in mortality. Of note, this was a small study. Dr. Cipolletta and his colleagues showed that starting colchicine when starting urate lowering therapy not only reduced the risk of gout flares but also reduced the risk of cardiovascular events by 18% over the next 6 months. And a meta-analysis by Dr. Xie and colleagues supports the impact of colchicine on reducing cardiovascular events with a 24% reduction, although this did not show a reduction in CV associated mortality.

Colchicine is not surprisingly better than NSAIDs to reduce the risk of major adverse cardiac events among gout patients. Dr. Yokose and colleagues showed that NSAID use was worse and more dangerous than no prophylaxis at all and compared with colchicine increased the risk of major adverse cardiac events by 56% and the hazard ratio for cardiovascular death was an astonishing 2.5 compared to using colchicine.

So in summary, gout increases the risk of all-cause mortality by 20 to 25% and increases the risk of specifically cardiovascular, infectious disease, digestive disease, and cancer associated mortality. And this is not improving over time. A treat-to-target approach that achieves a uric acid level less than 6.0 does slightly improve mortality and clearly improves the risk of cardiovascular events. Adding colchicine for prophylaxis certainly reduces the risk of
cardiovascular events. Larger studies however show that it does not seem to reduce gout associated mortality. This is Mark Fischer for RheumNow. Tune in for other great content. Thanks.