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Table 2 Hyperuricemia: clinical clusters at cardiovascular risk

From: Uric acid: A new look at an old risk marker for cardiovascular disease, metabolic syndrome, and type 2 diabetes mellitus: The urate redox shuttle

GROUPS Abbreviated Mechanisms
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