Recent Diuretic Use and the Risk of Recurrent Gout Attacks: The Online Case-Crossover Gout Study
DAVID J. HUNTER, MICHAEL YORK, CHRISTINE E. CHAISSON, RYAN WOODS, JINGBO NIU, and YUQING ZHANG
ABSTRACT. Objective. To assess several putative risk factors, including thiazide and loop diuretics use, thought to trigger recurrent gout attacks. Methods. We conducted an internet-based case-crossover study involving subjects who had a gout attack within the past year. Patients were recruited online and asked to provide access to medical records. Data were obtained on specific diuretic use on each day over the 2-day period prior to an acute gout attack (hazard period) and on each day of 2 days during the intercritical period (control period). We examined the relation of all diuretic use and use of specific diuretics, i.e., thiazide and loop, to the risk of recurrent gout attacks using a conditional logistic regression model adjusting for alcohol con- sumption and purine intake. Results. One hundred ninety-seven subjects completed both control and hazard period questionnaires. Participants were predominantly male (80%) and over half had a college education. The median time between onset of gout attack and logging on to the website was 2 days. Adjusting for alcohol con- sumption and purine intake, the odds ratio (OR) for recurrent gout attacks from all diuretic use over the last 48 h was 3.6 (95% confidence interval 1.4–9.7). OR of recurrent gout attacks were 3.2 and 3.8 for use of thiazide and loop, respectively. Conclusion. Recent use of diuretics is associated with a significantly increased risk for recurrent gouty arthritis. The increased risk of gout attacks from either thiazide or possibly loop diuretic therapies repre- sents an important modifiable risk factor in patients with gout. (J Rheumatol First Release June 1 2006)
Key Indexing Terms: DIURETICS
Gout affects about 8.4 per 1000 persons in the US1; epidemi- ologic data obtained from the last 4 decades are consistent with an increasing incidence and prevalence of gout in Western industrialized countries2. Although much is known about the pathophysiology of gout and clinically effective drug treatments are available, many patients with gout have
. These attacks cause progressive disability
and can lead to cumulative joint damage5. While a central therapeutic strategy in management of gout is avoidance of triggering events, investigations have concentrated on risk factors for initial occurrence of gout3,6-10 and few have explored factors that trigger recurrent attacks among individ- uals already diagnosed with gout.
From Boston University Clinical Epidemiology Research and Training Unit, Arthritis Cente , the Department of Medicine at Boston Medical Cente , and the Data Coordinating Cente , Boston University School of Public Health, Boston, Massachusetts, USA.
Supported by The Arthritis Foundation and NIH AR47785. Dr. Zhang was partly supported by Tap Pharmaceutical Co.
D.J. Hunte , MD; M. York, MD, Boston University Clinical Epidemiology Research and Training Unit; C.E. Chaisson, MD; R. Woods, MD, Data Coordinating Cente , Boston University School of Public Health; J. Niu, MD; Y. Zhang, MD, Boston University Clinical Epidemiology Research and Training Unit.
Address reprint requests to Dr. D.J. Hunte , A203, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA. E-mail: email@example.com
Accepted for publication February 26, 2006.
The association between hyperuricemia and diuretic thera- py has been known since 195811-13. Shortly after discovery of the thiazide class of diuretics, these medications were observed to raise serum uric acid levels. A similar effect was also later found for loop diuretics12. Diuretics raise uric acid levels through a combination of volume depletion and decreased renal tubular secretion of uric acid14. In a retro- spective cohort study of enrollees in the New Jersey Medicaid program, Gurwitz, et al14 found a 2-fold increased risk for ini- tiation of anti-gout medication in patients receiving thiazide diuretics. In a small case-control study of hypertensive patients who developed gout, gout was more strongly related to the use of loop diuretics than thiazides15. While knowledge of the association with hyperuricemia is clear, the relation of diuretic use as well as use of specific diuretics, such as thi- azide and loop, to the risk of recurrent gout attacks has not been formally investigated, and the magnitude of association, if existing, is unknown.
In addition to the burden of gout-related arthritis itself, patients with gout often have comorbidities including hyper- tension and coronary heart disease16. Further, hypertension itself is an independent risk factor for the development of gout17. Several investigators have hypothesized that signifi- cant increases over the last 2 decades in the prevalence of hypertension and concomitant diuretic therapy may contribute to the increased prevalence and incidence of gout in Western
Hunte , et al: Diuretics and recurrent gout