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Gout incidence is intertwined with serum urate, but only up to a point

 

Key clinical point: After 15 years of serum uric acid at 10 mg/dL or more, about half of people develop gout, likely leaving additional factors that contribute to its pathogenesis.

Major finding: The incidence of gout rose to about 1% after 15 years in patients with a serum uric acid (sUA) level of less than 6 mg/dL to almost 49% in those with 10 mg/dL or higher.

Data source: An analysis of 18,889 participants in four longitudinal observational cohort studies for whom baseline serum uric acid levels were available.

Disclosures: The Health Research Council of New Zealand supported the research. Dr. Dalbeth reported receiving consulting fees, grants, or speaking fees from Takeda, Horizon, Menarini, AstraZeneca, Ardea Biosciences, Pfizer, and Cymabay, but none are related to this study. Two other authors also had several financial disclosures, but none of the others did.


 

AT ACR 2017

 

– The incidence of gout is strongly linked to patients’ concentration of serum uric acid over time, but even so, less than half of patients with levels of 10 mg/dL or above develop the condition by 15 years, according to the largest individual person-level analysis to examine the relationship.

The incidence of gout rose from about 1% after 15 years in patients with a serum uric acid (sUA) level of less than 6 mg/dL to almost 49% in those with 10 mg/dL or higher in the study, which implies “a long period of hyperuricemia preceding the onset of clinical gout” and also “supports a role for additional factors in the pathogenesis of gout,” Nicola Dalbeth, MD, said in her presentation of the results at the annual meeting of the American College of Rheumatology.

A uric acid test tube. jarun011/Thinkstock
The cumulative incidence of gout in the study across 15 years of follow-up at 1-mg/dL intervals of sUA from less than 6 mg/dL to 10 mg/dL or more provides “estimates to guide discussion with hyperuricemic individuals about their risk of developing gout over time,” according to Dr. Dalbeth of the University of Auckland (New Zealand), and her colleagues.

Dr. Dalbeth and her associates found four studies in a search of PubMed and the Database of Genotype and Phenotype from Jan. 1, 1980, to June 11, 2016, that met the inclusion criteria of containing publicly available participant level data, recorded incident gout (via classification criteria, doctor’s diagnosis, or self report of disease), and had a minimum of 3 years of follow-up. The four studies were the Atherosclerosis Risk in Communities study, the Coronary Artery Risk Development in Young Adults study, the original cohort of the Framingham Heart Study, and the offspring cohort of the Framingham Heart Study, comprising 18,889 individuals who were gout free at the beginning of follow-up, which lasted a mean of 11.2 years.

In all studies combined, the incidence of gout at an sUA level of less than 6 mg/dL steadily increased from 0.21% at 3 years of follow-up to 1.12% at 15 years. In contrast, sUA at 10 mg/dL or higher led to gout in 10.00% at 3 years and in 48.57% at 15 years.

The same general pattern held for the incidence of gout in both men and women, although men had a higher incidence across nearly all sUA concentration ranges.

Female sex provided a 30% reduced risk of gout, and European ethnicity nearly halved the risk for gout, compared with non-Europeans, The risk for gout rose across decades of age, starting at 40-49 years, and also increased significantly for each 1-mg/dL interval of sUA starting at 6 mg/dL.

The study’s conclusions are limited by the use of variable definitions of gout and how it was ascertained. In addition, the study did not analyze other endpoints that are associated with hyperuricemia and may be relevant to discuss in counseling people with elevated sUA levels, such as hypertension, chronic kidney disease, and cardiovascular disease, Dr. Dalbeth said.

Audience member Daniel H. Solomon, MD, of Brigham and Women’s Hospital, Boston, said after the presentation that it is possible that age might not be independent of sUA level because it’s unknown when patients first had hyperuricemia, and so it could just serve as a marker of the duration of the effect of hyperuricemia. “You showed us that the longer you wait for people who have higher [sUA] levels, the more likely you are to observe gout. So it’s probably some mixture of duration [of hyperuricemia] and age,” he said.

Dr. Dalbeth agreed, saying that it could also help to explain why the incidence of gout is lower at younger ages in women but then subsequently becomes higher.

The Health Research Council of New Zealand supported the research. Dr. Dalbeth reported receiving consulting fees, grants, or speaking fees from Takeda, Horizon, Menarini, AstraZeneca, Ardea Biosciences, Pfizer, and Cymabay, but none are related to this study. Two other authors also had several financial disclosures, but none of the others did.
 
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