The presence of tophi - crystal deposits of uric acid found on the surface of the joints or in the skin and cartilage - in people with gout can increase their risk of developing cardiovascular disease, according to research presented this week at the American College of Rheumatology Annual Meeting in San Francisco.
Gout is a painful and potentially disabling form of arthritis that has been recognized since ancient times. Initial symptoms usually consist of intense episodes of painful swelling in single joints, most often in the feet (especially the big toe). Gout is caused by monosodium urate crystals that precipitate in and around joint structures. Acute attacks of gout are treated with anti-inflammatory medications, such as NSAIDs, colchicines and corticosteroids. Agents that lower serum uric acid levels, such as allopurinol and febuxostat, are used to prevent disease flares.
Cardiovascular disease is a common complication of many rheumatic diseases. Despite this, there have been few, if any, studies that look at cardiovascular risk in the different stages of gout, so researchers based in Bulgaria recently embarked on a study that did just this.
"More than half of the deaths in the world are caused by cardiovascular diseases, and chronic inflammation is a proven risk factor," says lead investigator in the study, Rada Gancheva, MD, a resident at the University Rheumatology Clinic; St. Iv. Rilski; Sofia, Bulgaria. "Therefore, in recent decades the efforts of scientists have been focused on the early detection of risk factors and the possibilities to influence them. Some researchers consider that high serum uric acid is such a risk factor. Others turned their attention to gout, and proved that between gout attacks chronic inflammation is maintained. Analyzing these studies — and based on data that gouty tophi are not passive masses, but rather active granulomas — we decided to examine the different stages of gout and to compare the results."
Dr. Gancheva's team recruited 170 people to their study and divided them into four groups. The first group included 35 people — 20 of which were women; 15 were men —with an average age of 61 and a diagnosis of osteoarthritis. This group had conventional cardiovascular disease risk factors—such as high blood pressure, diabetes mellitus, obesity, dyslipidemia, reduced creatinine clearance, and smoking — and had normal levels of serum uric acid and no history of gout attacks. This group was considered the control group, and the other groups would be compared to them.
The other three groups were all in the stages of developing or having gout. The second group included 41 people (18 women and 23 men) with elevated levels of serum uric acid (called asymptomatic hyperuricemia) with an average age of 55 years. The third group included 52 people (seven women and 45 men) with gout who did not have tophi present with an average age of 56. The fourth group included 42 people (one woman and 41 men) with an average age of 59 who had gout and had tophi present.
All patients underwent a complex multimodal ultrasonography that included examination of the kidneys and measurement of renal resistive index (which reflects intrarenal blood flow); echocardiography to assess left ventricular hypertrophy and diastolic function of the heart; and examination of common carotid arteries for determination of thickening, stiffening of carotid arteries and blood flow.
The researchers analyzed the participants' test results to see how the patients in the three stages of gout compared with each other and with the patients who had osteoarthritis when it came to cardiovascular risks. There were no significant differences between the four groups of patients in the frequency of diabetes mellitus, arterial hypertension, cardiovascular events, chronic renal failure and obesity. However, the percentage of smokers was significantly lower in the group with asymptomatic hyperuricemia and 100 percent of the patients with gout (without tophi and with tophi) had dyslipidemia.
By conducting logistic regression to account for these differences, Dr. Gancheva's team found the presence of tophi in gout independently increased the risk of developing thicker and stiffer carotid arteries, a marker for increased risk of cardiovascular disease. In fact, the presence of tophi increased the risk of stiffer carotid arteries three times more than arterial hypertension. According to Dr. Gancheva, "These data suggest that the presence of tophi may confer an independent risk for cardiovascular disease that commensurable and even greater than that for hypertension." Based on these findings, Dr. Gancheva says, "With more studies like this one, with such an integrated approach, we believe criteria for the assessment of cardiovascular risk in gout could be established and easily applied by physicians to better ensure quality of care for people with gout."
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