Table 2 Hyperuricemia: clinical clusters at cardiovascular risk

Patients with CVD

Accelerated atherosclerosis

Congestive heart failure

Increased apoptosis – necrosis of the arterial vessel wall and capillary resulting in increased purine metabolism and hyperuricemia.

Increased oxidative – redox stress

Antioxidant – Prooxidant Paradox:

Urate Redox Shuttle

Patients with (T2DM)

Accelerated atherosclerosis

(Atheroscleropathy)

Acting through obesity and insulin resistance.

Accelerated atherosclerosis with increased vascular cell apoptosis and inflammatory necrosis with increased purine metabolism resulting in hyperuricemia and increased oxidative stress through ischemia-reperfusion and xanthine oxidase.

Additional reductive stress associated with glucotoxicity and pseudohypoxia.

Increased oxidative-redox stress

Antioxidant – Prooxidant Paradox:

Urate Redox Shuttle

Obesity – Insulin resistance

Hyperinsulinemia – Insulin toxicity

Metabolic Syndrome (figure 1):

Hyperinsulinemia

Hypertension

Hyperlipidemia dyslipidemia, obesity

Hyperglycemia

Leptin may induce hyperuricemia.

Insulin increases sodium reabsorption and is tightly linked to urate reabsorption.

Increased oxidative – redox stress

Antioxidant – Prooxidant Paradox:

Urate Redox Shuttle

Men and Postmenopausal females

Estrogen is uricosuric

Renal diseases

Decreases in GFR increases uric acid levels

Hypertension

Urate reabsorption increased in setting of increased renal vascular resistance, microvascular disease predisposes to tissue ischemia that leads to increased urate generation (excess purine metabolism) and reduced excretion (due to lactate competing with urate transporter in the proximal tubule).

Increased oxidative – redox stress

Antioxidant – Prooxidant Paradox:

Urate Redox Shuttle

African American

Unknown (assumed genetic causes as yet unidentified)

Diuretic use

Volume contraction promotes urate reabsorption

Alcohol use (in excess)

Increases urate generation and decreased urate excretion