Urate Lowering Therapy Could Prevent Death Associated with Cardiovascular Disease in People with Gout

Newswise — The use of urate lowering therapy might successfully prevent death from cardiovascular disease in people with gout, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Atlanta.

Hyperuricemia is an abnormally high level of uric acid in the blood that can lead to gout – a painful and potentially disabling form of arthritis that has been recognized since ancient times. Initial symptoms of gout usually consist of intense episodes of painful swelling in single joints, most often in the feet (especially the big toe). Gout occurs when excess uric acid (a normal waste product) accumulates in the body, and needle‐like crystals deposit in the joints. This may happen because uric acid production increases or, more often, the kidneys are unable to remove uric acid from the body adequately.

Previous studies have confirmed that there is an association between elevated serum uric acid levels and cardiovascular disease. Based on this information, researchers recently evaluated whether controlling serum acid levels with urate lowering therapy—drugs that also reduce gout flare ups and joint damage and deformity from gout—could help prevent the development of, and death from, cardiovascular disease in people with gout.

The researchers examined medical data on 45,215 participants—of whom 20,677 were men and 24,538 were women—from the MJ Health Clinical Center in Taiwan, the National Health Insurance database, and the National Mortality Registry for Cardiovascular Death to look for links between high levels of uric acid, urate lowering therapies and cardiovascular disease. While completing their comparison of information, the researchers took into account a number of other factors that could contribute to the development of and death from cardiovascular disease including age, gender, high blood sugar, high blood pressure, kidney disease, heart disease, arthritis, high cholesterol, and several drugs used to treat these conditions. Additionally, they considered if a person was overweight, had a history of cigarette smoking, and his or her level of alcohol consumption, level of exercise, education, occupation and work load.

Over an average of 11.3 years follow up, 519 subjects died of cardiovascular disease, including 308 men and 211 women. Urate lowering therapy reduced the risk of cardiovascular disease by 44 percent and reduced death from a stroke by 58 percent. Urate lowering therapy was also associated with a reduction in death from hemorrhagic stroke and high blood pressure of 88 percent and 71 percent, respectively.

Additionally, these researchers found that subjects who continued treatment for hyperuricemia for more than one year had a much lower risk of developing cardiovascular disease when compared to those who had been treated for less than two months.

“There is potential benefit of urate lowering therapy on reducing total cardiovascular disease and stroke mortality,” says Jiunn-Horng Chen, MD, PhD; assistant professor of medicine at China Medical University and lead investigator of the study. “Patients with hyperuricemia should be treated more aggressively and persistently than previously thought. This is not only for preventing incident gout, but also for the sake of cardiovascular disease prevention.”

Patients should talk to their rheumatologists to determine their best course of treatment.

The American College of Rheumatology is an international professional medical society that represents more than 8,000 rheumatologists and rheumatology health professionals around the world. Its mission is to advance rheumatology. The ACR/ARHP Annual Scientific Meeting is the premier meeting in rheumatology. For more information about the meeting, visit www.rheumatology.org/education or join the conversation on Twitter by using the official hashtag: #ACR2010.

Editor’s Notes: Jiunn-Horng Chen, MD, PhD, will present this research during the ACR Annual Scientific Meeting at the Georgia World Congress Center at 12:15 PM Wednesday, November 10 in Hall A3. Dr. Horng Chen will be available for media questions and briefing at 8:30 AM on Wednesday, November 10 in the on-site press conference room, B 212

Learn more about living well with rheumatic disease as well as rheumatologists and the role they play in health care.

Presentation Number: 2088

Effects of urate lowering therapy on cardiovascular mortality: A Taiwanese cohort study

Jiunn-Horng Chen, MD, PhD (School of Medicine, China Medical University, Taichung, Taiwan Division of Rheumatology, Internal Medicine Department, China Medical University Hospital, Taichung, Taiwan) Wen-Harn Pan, PhD (Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University Nutrition Medicine Program, Institute of Population Health Sciences, National Health Research Institutes, Taiwan)

Body: Objective: Gout and elevated serum uric acid (sUA) level have been associated with cardiovascular disease (CVD); however, whether urate lowering therapy (ULT) is beneficial is still inconclusive. This study aimed to clarify whether controlling sUA with ULT can improve outcomes of CVD.

Method: This prospective cohort study linked baseline clinical data of examinees from the MJ Health Clinical Center in Taiwan with drug dispensed database from the National Health Insurance, and outcome information from the National Mortality Registry for CVD death (ICD-9 code 390-459). Multivariate Cox proportional hazard model was applied to adjust for confounders including age, sex, hyperuricemia (>7.7 mg/dl for men or >6.6 mg/dl for women), overweight (BMI >24 kg/m2), hyperglycemia (>100 mg/dl), hypertension (SBP 130 mmHg, or DBP 80 mmHg), hypercholesterolemia (>200 mg/dl), hyper-triglyceridemia (>150 mg/dl), renal insufficiency (GFR <90 ml/min per 1.73 m2), and heart disease, kidney disease, arthritis, prior use of antihypertensive, anti-diabetic, steroid or analgesics, cigarette smoking, alcohol consumption, exercise, education, occupation, and working load.

Results: Among 45,215 participants (20,677 men and 24,538 women), 519 subjects died of CVD (308 men and 211 women) after a mean follow-up of 11.3 years. A preventive effect of ULT on CVD and stroke mortality was defined with respective hazard ratio (HR) of 0.56 (95% confidence interval, 0.46-0.70) and 0.42 (0.29-0.59) after multivariate adjustment. These effects were prominent for mortalities of hemorrhagic stroke and hypertension with corresponding HR of 0.12 (0.05-0.28) and 0.29 (0.13-0.63). Comparing with participants who did not use ULT, the users who continued treatment until outcome event or censor had better outcome (HR, 0.32; 0.21-0.49) than subjects who discontinue ULT for more than one year (HR, 0.68; 0.53-0.84). In the renal failure status (glomerular filtration rate <30 ml/min per 1.73 m2), allopurinol usage was more beneficial (HR, 0.04; 0.01-0.25) than benzbromarone (HR, 0.60; 0.11-3.18) for CVD outcomes.

Conclusion: This study demonstrates a preventive effect of ULT for CVD mortality. Further replication studies are needed in the future. Disclosure: Jiunn-Horng Chen, nothing to disclose; Wen-Harn Pan, nothing to disclose.

View press release with full abstract at www.rheumatology.org