Excess Non-CV Mortality Persists in Gout Save

Patients with gout not only have a well-recognized increased risk of dying from cardiovascular (CV) disease, but also have higher all-cause mortality and die prematurely from other diseases, a Swedish study indicated.

In an analysis that included more than 800,000 individuals, patients with gout had a 17% higher risk of death from any cause compared with those without gout (HR 1.17, 95% CI 1.14-1.21), according to Aleksandra Turkiewicz, PhD, of Lund University, and colleagues.

For specific diseases, the strongest association was seen for renal diseases, with an almost 80% increased risk of mortality (HR 1.78, 95% CI 1.34-2.35), the researchers reported in Arthritis & Rheumatology.

The overall burden of excess mortality has recently been declining, particularly because of decreased mortality from cardiovascular disease. However, this has not been the case for patients with gout, with a recent study showing persistent elevated mortality in these patients.

"Whether this finding of a stable premature mortality gap remains true for the 21st century, and what comorbidities may be contributing to the excess burden of mortality beyond CV diseases in persons with gout requires clarification," Turkiewicz and colleagues stated.

Accordingly, they analyzed outcomes from several Swedish national databases for individuals living in Skåne County (the country's southernmost county, adjacent to Denmark) from 1998 to 2002 who were then followed from 2003 to 2013 to identify new cases of gout. These cases were age- and sex-matched with individuals without gout, and compared for mortality rates from CV disease, renal disease, dementia, diabetes, digestive diseases, pulmonary disease, infection, neoplasm, and other causes such as urinary tract problems and falls.

Among 832,258 individuals, there were 19,497 new diagnoses of gout; these were matched with 194,947 controls. Mean age was 70 and 68% were men. Patients with gout had higher rates of many comorbidities, including hypertension, ischemic heart disease, and chronic kidney disease. Women were older than men at the time of gout diagnosis (74.7 vs 67.9 years). 

During a median follow-up of 4.2 years, there were 5,881 deaths in the gout group and during 4.5 years of follow-up, there were 46,268 deaths among controls. The all-cause mortality rate was 63.6/1,000 person-years for patients with gout and 47.3/1,000 among controls.

For both gout patients and controls, CV disease was the most common cause of death, occurring in 49.5% and 41.3%, respectively, for an adjusted hazard ratio of 1.27 (95% CI 1.22-1.33).

Increased mortality risks for other non-CV causes were seen for diseases of the digestive system (HR 1.56, 95% CI 1.34-1.83) and infections (HR 1.20, 95% CI 1.06-1.35), while the risk of death associated with dementia was decreased (HR 0.83, 95% CI 0.72-0.97).

There also were differences when the analysis was stratified by sex. The excess all-cause mortality was greater among women than men, with hazard ratios of 1.23 (95% CI 1.17-1.30) and 1.15 (95% CI 1.10-1.19), respectively.

For renal diseases, women also had much higher risks (HR 4.19, 95% CI 2.81-6.23) than men (HR 1.38, 95% CI 0.97-1.97), and for infections, the risk again was greater for women (HR 1.51, 95% CI 1.25-1.83) than for men (HR 1.05, 95% CI 0.90-1.23). 

This is one of the few studies of gout mortality that included a large number (32%) of women, and precise estimates of mortality risks have therefore been lacking for women, the authors pointed out. The apparent higher risks for women may reflect their lower background mortality risk, "although we cannot rule out a possible real difference since women with gout are older and seem to be sicker than men," they wrote.

Death from renal disease among gout patients may have various explanations, including hyperuricemia-related vascular and interstitial damage, and the frequent use of medications such as diuretics and nonsteroidal anti-inflammatory drugs (NSAIDs) for acute attacks. "With the increasing body of evidence suggesting a protective renal effect of urate-lowering therapies, the results of our study of high risk of death related to renal diseases among gout subjects reinforce the need for better gout care," the researchers noted.   

In addition, the risks for gastrointestinal-related mortality may relate to the use of medications such as NSAIDs and prednisone, which also may enhance the risk for infection-related death.

Analysis of the risk for dementia-associated death in gout patients was a novel aspect of this study. Previous studies considering urate levels and dementia have had contradictory findings, with some showing lower risks because of the antioxidant properties of urate, and others suggesting higher risks because urate may also have pro-oxidant effects in certain circumstances.

"Therefore, urate may play complex and different roles in the central nervous system depending on its concentration, microenvironment, and other factors," Turkiewicz's group explained.

The study highlights the necessity for improved management of comorbidities in patients with gout, they concluded.

A limitation of the study was its reliance on registry data.

One author has received support from the National Institutes of Health. All stated that they have no financial conflicts.