Gout, Hyperuricemia Linked to Higher Comorbidities

Troy Brown

June 25, 2012

June 25, 2012 — Individuals with gout or hyperuricemia have a higher prevalence of major comorbidities, including hypertension, chronic kidney disease, diabetes, and obesity, according to a study published in the July issue of the American Journal of Medicine.

Yanyan Zhu, PhD, a research assistant professor in the Clinical Epidemiology Unit at Boston University School of Medicine in Massachusetts, and colleagues used data on 5707 participants from the National Health and Nutrition Examination Survey (NHANES) 2007-2008 to calculate the national prevalence and population estimates of 8 major comorbidities in patients with gout and hyperuricemia compared with in individuals without those conditions.

The NHANES is a nationally representative sample of men and women in the United States. Participants were adults aged 20 years and older for whom interview, examination, and laboratory data were available.

All NHANESs conducted between 1999 and 2008 have collected serum urate data, so the researchers also analyzed the data of 24,693 participants from those 10 years to calculate more precise estimates of comorbidity prevalence associated with various serum urate levels.

Commenting on the study for Medscape Medical News, Herbert S.B. Baraf, MD, FACP, FACR, said, "Gout is probably underdiagnosed, as painful as it is. In women, it's because it doesn't present in the usual fashion, and hyperuricemia, which is quite prevalent, is under-recognized because it's no longer a part of standard screening."

Dr. Baraf is the managing partner of Arthritis & Rheumatism Associates in Wheaton, Maryland, and a clinical professor of medicine at George Washington University in Washington, DC.

Overall, 3.9% of adults studied reported a diagnosis of gout. Of these, 73.9% (6.1 million) had hypertension, 71.1% (5.5 million) had stage 2 or worse chronic kidney disease, 53.3% (4.3 million) were obese, 25.7% (2.1 million) had diabetes, 23.8% (2.0 million) had nephrolithiasis, 19.9% had stage 3 or worse chronic kidney disease, 14.4% (1.2 million) had myocardial infarction, 11.2% (0.9 million) had heart failure, and 10.4% (0.9 million) had stroke.

Compared with individuals without gout, the age-and sex-adjusted odds ratios (ORs) were 4.19 (95% confidence interval [CI], 2.75 - 6.39) for hypertension, 2.68 (95% CI, 1.88 - 3.83) for heart failure, 2.37 (95% CI, 1.54 - 3.65) for myocardial infarction, 2.36 (95% CI, 1.49 - 3.73) for diabetes, 2.35 (95% CI, 1.55 - 3.57) for obesity, 2.32 (95% CI, 1.65 - 3.26) for stage 3 or worse chronic kidney disease (glomerular filtration rate [GFR] < 30), 2.10 (95% CI, 1.39 - 3.18) for nephrolithiasis, 2.02 (95% CI, 0.98 - 4.19) for stroke, and 1.75 (95% CI, 1.23 - 2.49) for stage 2 or worse chronic kidney disease (GFR < 60) .

When the analyses were stratified by sex, women with gout tended to have comorbidities more frequently than men with gout, except for obesity, nephrolithiasis, and stage 2 or worse chronic kidney disease. After adjustment for age, ORs for heart failure were 5.84 among women and 1.72 among men (P for interaction < .001), for myocardial infarction, they were 6.86 among women and 1.45 among men (P for interaction = .012), and for diabetes they were 4.23 among women and 1.73 among men (P for interaction = .006).

Prevalence of Comorbidities Increases as Hyperuricemia Levels Rise

Using the data from the NHANES 2007-2008 study, the researchers looked at the prevalence of comorbidities in US adults with hyperuricemia. They found the overall prevalence of hyperuricemia (serum urate level > 7.0 mg/dL among men and serum urate level > 5.7 mg/dL among women) among US adults was 21.4%. Overall, the mean serum urate level was 6.14 mg/dL (95% CI, 6.06 - 6.23 mg/dL) among men and 4.87 mg/dL (95% CI, 4.79 - 4.94 mg/dL) among women.

Of the participants with hyperuricemia, 61.4% had stage 2 or worse chronic kidney disease, 54.4% were obese, 49.7% had hypertension, 14.8% had stage 3 or worse chronic kidney disease, 13.5% had diabetes, 12.3% had nephrolithiasis, 5.7% had stroke, 5.1% had myocardial infarction, and 5.1% had heart failure.

Using the combined NHANES data from 1999-2008, the researchers analyzed the comorbidities according to serum urate level categories with 1-mg/dL increments because this allowed larger sample sizes in each serum urate level category.

Increasing levels of hyperuricemia were associated with graded increases in comorbidity prevalence. The highest serum urate level category (≥10 mg/dL) had a prevalence of 85.9% for stage 2 or worse chronic kidney disease, 66.0% for hypertension, 65.3% for obesity, 53.5% for stage 3 or worse chronic kidney disease, 32.9% for heart failure, 32.6% for diabetes, 23.1% for myocardial infarction, and 11.7% for stroke. These findings were similar to the analyses limited to the NHANES 2007-2008 data.

Sex-stratified analyses of serum urate level outcomes found a higher prevalence of comorbidities in women than men in the same serum urate level categories.

"When you see a person with high uric acid, you're probably looking at someone who's diabetic, hypertensive, hypercholesterolemic...these things are commonly seen together. Sometimes it's the gout that brings these other things to the clinical forefront. Sometimes it's the presence of these things that should raise the suspicion of gout," Dr. Baraf said.

"The presence of gout or hyperuricemia, particularly at higher levels, should trigger a high level of clinical suspicion and investigation for the potential coexistence of these comorbidities. If present, comorbidities need to be recognized as factors potentially more life-threatening than gout or hyperuricemia, and must be appropriately managed," write the authors in the journal.

There is the question of what to do about patients who have high uric acid levels but no clinical signs of gout, said Dr. Baraf. Medical management of asymptomatic hyperuricemia is not currently recommended, at least not with drugs to lower the uric acid, he said.

"Patients who have asymptomatic hyperuricemia typically have some of these comorbidities, so those things can be treated more aggressively. If one controls hypertension better, one decreases the risk of subsequent heart disease, and subsequent renal disease. So this plays more into prevention, not of hyperuricemia, but of those comorbidities, and tighter control of those comorbidities is essential for outcomes of cardiovascular disease and for diabetes," said Dr. Baraf.

"But in the absence of gout, we're not recommending that the hyperuricemia itself be treated," Dr. Baraf said.

The study was supported by Takeda Pharmaceuticals International Inc. One author is an employee of Takeda Pharmaceuticals International Inc; another author has received research funding for other projects from Takeda Pharmaceuticals and has served on advisory boards for Takeda Pharmaceuticals, URL Pharma, and Savient Pharmaceuticals. Dr. Baraf has done speaking for Takeda, speaking and consulting for Savient, and consulting for Ardea, as well as clinical trials for all 3 of those companies.

Am J Med. 2012;125:679-687. Abstract