A new large-scale study led by researchers at the University of Nottingham has found that drugs commonly used to treat gout may also reduce the risk of heart attacks and strokes in people with the condition.
The findings, published in JAMA Internal Medicine, suggest that lowering blood uric acid levels to recommended targets not only relieves gout symptoms, but may also help prevent serious cardiovascular events. The study was led by Professor Abhishek from the University of Nottingham’s School of Medicine, in collaboration with colleagues from Keele University and the London School of Hygiene & Tropical Medicine in the UK, the University of Gothenburg in Sweden and the Marche Polytechnic University in Italy.
What is Gout and Why Does it Matter?
Gout is an inflammatory joint disease caused by persistently high levels of uric acid in the blood. Uric acid is produced during the breakdown of purines, which are both produced by the body itself and absorbed through food. If the body produces more uric acid than it can excrete via the kidneys, hyperuricemia occurs. If the concentration exceeds a certain limit, needle-shaped uric acid crystals are deposited in the joints and surrounding tissue. These crystals trigger a strong immune reaction, which leads to the typical sudden and very painful inflammation. The metatarsophalangeal joint of the big toe is particularly frequently affected, but other joints can also be involved.
However, the significance of gout goes beyond acute pain. It is now understood as a systemic disease that is closely linked to other health problems. People with gout have an increased risk of cardiovascular diseases such as heart attack or stroke. In addition, it often occurs together with high blood pressure, obesity, diabetes or kidney disease. Gout is therefore also considered an indication that the metabolism as a whole is out of balance and may require more comprehensive medical care.
Treatment aims not only to alleviate acute symptoms, but above all to reduce uric acid levels in the long term. A commonly used medication is allopurinol, which inhibits the formation of uric acid in the body by blocking the enzyme xanthine oxidase. If taken consistently and in the correct dose, the uric acid level can be permanently reduced, gradually dissolving crystals that have already been deposited and preventing new attacks. It is important that the therapy is continuous, as discontinuation or irregular intake jeopardizes the success of the treatment. In some cases, alternative medication is used, for example if allopurinol is not tolerated.
Gout is widespread in Europe and affects around two to three percent of the adult population, with an upward trend. Medical care is based on guidelines, such as those of the European Alliance of Associations for Rheumatology, which set clear target values for uric acid levels and recommendations for treatment. In addition to medication, lifestyle also plays an important role: a low-purine diet, limited alcohol consumption, weight reduction and sufficient fluid intake can make a significant contribution to controlling the disease. Overall, gout can be treated well today, but requires long-term and consistent care in order to avoid both acute symptoms and secondary diseases.
Lowering Uric Acid Levels for Better Results
Previous research has shown that patients who lower their serum uric acid levels to below 360 micromol/l (6 mg/dl) experience fewer gout attacks. However, it remained unclear whether achieving this goal could also reduce the risk of heart attack and stroke. To investigate this, the researchers tested whether achieving a serum uric acid level below 360 micromol/L (6 mg/dL) through urate-lowering therapy, primarily with allopurinol, would lead to improved cardiovascular outcomes.
Professor Abhishek said: “People with gout are at increased risk of conditions such as heart disease and stroke. This is the first study to find that drugs such as allopurinol, which are used to treat gout, reduce the risk of heart attack and stroke when taken at the right dose. The correct dose varies from person to person and is the dose that lowers the uric acid level in the blood to below 360 micromol/l (6 mg/dl).”
Lower Risk of Heart Attack, Stroke and Death
The research team analyzed data from primary care records in the Clinical Practice Research Datalink Aurum, which were linked to hospital and mortality data between January 2007 and March 2021. The study included adults aged 18 years and older who had been diagnosed with gout and had serum uric acid levels above 360 micromol/L (6 mg/dL) prior to treatment. Using an “emulated target trial” approach, which relies on existing health data rather than traditional clinical trials, the researchers were able to analyze the results more quickly and efficiently.
The participants were divided into two groups. One group reached the target uric acid level of less than 360 micromol/l (6 mg/dl) within 12 months of starting urate-lowering therapy. The other group did not reach this target within the same period. The researchers then tracked whether the participants experienced a major cardiovascular event (i.e. heart attack, stroke or death due to cardiovascular disease) within five years of starting treatment.
Among nearly 110,000 patients, those who achieved target uric acid levels had higher survival rates and a lower likelihood of a major cardiovascular event than those who did not. The protective effect was even stronger in people who were already at high or very high cardiovascular risk. Patients who achieved an even lower uric acid level of less than 300 micromol/L (5 mg/dL) showed a greater reduction in risk. In addition, patients in the target value group had fewer gout attacks overall.
Study Underlines Double Benefit of Gout Therapy
“The results of our study are very positive and show that gout patients who were prescribed uric acid-lowering medication and who achieved serum uric acid levels below 360 micromol/L (6 mg/dL) within 12 months had a significantly lower risk of heart attack or stroke over the following five years. Previous research from Nottingham showed that targeted urate-lowering treatment prevents gout attacks. The current study provides an additional benefit in terms of reduced risk of heart attack, stroke and death from these conditions,” said Professor Abhishek. Overall, the results suggest that appropriate treatment of gout by achieving recommended urate targets may provide important benefits beyond joint health, including significant protection against serious heart disease.