Background/Purpose:  Elevated serum uric acid (sUA) levels, with and without gout, are associated with systemic inflammation, coronary artery disease (CAD), chronic kidney disease, and diabetes. Patients with asymptomatic hyperuricemia may have subclinical urate deposits in joints and arteries. Positron emission tomography (PET)-measured coronary flow reserve (CFR) is a senstive marker of myocardial perfusion and a quantitative predictor of clinical CAD risk.  Patients with CFR <2.0 are at increased risk for major adverse cardiac events and cardiac death. We aimed to determine the association between sUA levels and CFR, insulin resistance, renal function, systemic inflammation, and subclinical urate deposits in patients with asymptomatic hyperuricemia and metabolic syndrome.   

Methods: Adults aged ≥40 years with sUA levels ≥6.5 mg/dl and metabolic syndrome according to the National Cholesterol Education Program –Adult Treatment Panel III criteria were eligible. Patients with gout, nephrolithiasis, symptomatic CAD or pulmonary disease and those using xanthine oxidase inhibitors or probenecid were excluded. We assessed resting and stress induced (after adenosine infusion) myocardial blood flow (MBF) using a cardiac PET and calculated CFR from these data. We also measured sUA, IL-6, high-sensitivity c-reactive protein (hs-CRP), serum creatinine, insulin resistance by homeostatic model assessment (HOMA-IR) method, and urate deposits using dual-energy CT (DECT) of the foot and carotid arteries.    

Results: We conducted an interim analysis including 18 subjects (Table) with the mean (SD) age of 66.0 (7.4) years and mean (SD) sUA level of 8.1 mg/dl (1.1). The mean (SD) CFR was abnormaly low at 1.9 (0.4) and the mean (SD) stress MBF was 1.5 (0.4) ml/min/g. On univariate regression analyses, sUA had no signficant association with CFR (β=-0.05, p=0.9), stress MBF (β=0.17, p=0.7), IL-6 (β=-1.14, p=0.5), serum creatinine (β=0.31, p=0.5) HOMA-IR (β=0.95, p=0.5), hs-CRP(β=-5.45, p=0.06), and eGFR (β=-0.76, p=0.15). Four patients (22.2%) were found to have urate deposits in the foot by DECT with urate volume ranging between 0.01 to 0.39 cm³. None had urate deposits in the carotid arteries.            

Conclusion: In this interim analysis of the pilot study involving patients with asymptomatic hyperuricemia, no relationship was noted between sUA and CFR and other cardiometabolic markers. However, we found urate deposits in the foot in over one-fifth of the patients. Final analyis that further determines the link bewteen sUA and cardiometabolic risk in patients with asymptomatic hyperuricemia and metabolic syndrome is underway.