Presence of the metabolic syndrome results in a three-fold increased risk of atherosclerotic cardiovascular disease and a five-fold increased risk of type 2 diabetes. Higher insulin levels are known to reduce renal excretion of urate, Dr. Choi said.
Several studies have shown an independent association with serum uric acid and future risk of cardiovascular disease, stroke, and hypertension. The Coronary Artery Risk Development in Young Adults (CARDIA) study with 4,053 young adults found significantly higher body mass index, fasting insulin, and triglycerides and lower HDL cholesterol in patients with hyperuricemia.
The National Health and Nutrition Examination Survey III reported a 63% prevalence of the metabolic syndrome among patients with gout.3 In a Mexican case series, the prevalence was 82%, and in a Korean series, it was 44%.4,5
According to Dr. Choi, the British Columbia Linked Health Database found that women with gout have a 39% increased risk of myocardial infarction, whereas the increased risk for men was 11%.
Dr. Choi said that any patient with gout or hyperuricemia should trigger in the physician a “high clinical suspicion and investigation for potential coexistence of the metabolic syndrome and associated comorbidities.”
He stressed that, “every diagnosis of gout should raise a red flag to alert the physician to assess whether the patient is at risk for cardiovascular disease.”
Gout treatment should mirror treatment for hypertension, he noted, with lifestyle and dietary changes. The prevalence of gout has doubled since the 1970s, which could be related to the prevalence of high-fructose corn syrup in the American diet. Sweetened soft drinks should be eliminated because they have been found to increase the risk of gout twofold, Dr. Choi said.
Hypertensive patients with gout and the metabolic syndrome should be treated with losartan or amlodipine, which has a better risk–benefit ratio than diuretics for these patients, he said.
Biologic Activity of Uric Acid
According to Michael H. Pillinger, MD, associate professor of medicine and pharmacology at New York University Langone Medical Center in New York, uric acid seems to be a danger signal that drives the immune response. “A damaged, virally infected cell that is dying makes uric acid, and if it makes enough locally, you will get crystals forming and an immune response near the cell,” he said. “But it’s a fail-safe mechanism for not spreading the response where it doesn’t belong. Uric acid is a danger signal that acts as endogenous adjuvant when tissue is injured during immune presentation.”
