Hyperuricemia has for many years been linked to cardiovascular diseases, such as hypertension, coronary artery disease, peripheral vascular disease and stroke.16-18 In 2011, a meta-analysis showed that for every 1 mg/dL increase in serum uric acid there is a 13% increased risk for hypertension.19
A growing number of studies are demonstrating that hyperuricemia is an independent risk factor for progression of chronic kidney disease.20,21
Evidence is growing that chronically elevated serum uric acid can contribute to a variety of health problems, including type II diabetes, hypertension, vascular disease & chronic kidney disease.
There is a paucity of human studies attempting to demonstrate the benefits of treating asymptomatic hyperuricemia. Animal studies have shown the benefit of xanthine oxidase inhibition preventing vascular complications of insulin resistance.22,23 Several studies have shown the benefits of allopurinol, febuxostat and oxipurinol (the active metabolite of allopurinol) in myocardial function.24-26
In 2008, a double-blind, placebo-controlled, crossover study demonstrated that allopurinol successfully lowered blood pressure in hypertensive adolescents, suggesting that allopurinol could be as effective as most conventional antihypertensive drugs.27 A model designed to simulate the effects of uric acid lowering with allopurinol predicted that a significant reduction of vascular events, such as stroke and myocardial infarction, could be achieved in men with serum urate levels >7.0 mg/dL and women with levels >5.0 mg/dL.28 A randomized, open, parallel-controlled study in patients with type II diabetes and asymptomatic hyperuricemia showed that allopurinol improved insulin resistance, reduced serum levels of high-sensitivity C-reactive protein and reduced carotid intima-media thickness, suggesting a delay in development of atherosclerosis.29 Kidney function was also significantly improved in this group.30
A retrospective study following 111,992 patients with a serum uric acid level >7.0 mg/dL over nine years showed that urate-lowering therapy treated patients who achieved a serum uric acid level <6.0 mg/dL had 37% reduction in renal disease progression.20
Drug Therapies
So should we be treating asymptomatic hyperuricemia?
We do not routinely monitor uric acid levels in patients with at-risk diseases who do not have gout. Should we be testing more frequently?
Allopurinol is an inexpensive and relatively safe medication. Two synthetic uricase products are available for clinical use: Pegloticase (Kreystexxa) is now marketed for treatment refractory gout and rasburicase (Elitek) for prevention and treatment of tumor lysis syndrome, but because of the relatively high rates of side effects, these are not practical for use in most patients with hyperuricemia.
More than 30 studies can be found on ClincalTrials.gov—recruiting, active or completed—where uric acid lowering with allopurinol or febuxostat is being tested for effects on insulin resistance, hypertension, kidney disease, heart failure, left ventricular hypertrophy and vascular disease. Perhaps, we will soon have answers as to how to survive the evolutionary advantage that has failed us in the modern world.
