Serum uric acid and cardiovascular disease.
Year: 2010
Type: article
Abstract: The relationship between the serum uric acid (SUA) and gout, hypertension and obesity has been known since the late 19th century. After 1960s many epidemiological studies confirm the relationship between the SUA level and various cardiovascular diseases, such as arterial hypertension, atherosclerosis, stroke, acute and chronic heart failure. This relationship is observed not only in frank hyperuricemia (defined by SUA > 7 mg in men and > 6 mg in women), but also in the high – normal values of SUA (defined by SUA > 5.5 mg/dl) (1, 2). The significance of this association is still unknown and in literature there are controversies concerning the significance of hyperuricemia in cardiovascular disease.
Uric acid is the final oxidation product of purine catabolism in humans and in higher primates. The last metabolic step, the conversion of hypoxanthine to uric acid is regulated by the enzyme xanthine oxidoreductase (XO). The major sources of XO are the liver and the small intestine, but there are evidences for local production of XO by the endothelium and the myocardium. As a part of this process reactive oxygen species (ROS) are produced (Figure (Figure1).1). XO activity is up-regulated in many cardiovascular diseases, such as myocardial ischemia, reperfusion injury, left ventricular remodeling after myocardial infarction and heart failure and is associated with enhanced oxidative stress.
Figure 1
Uric acid synthesis: In humans uric acid is the terminal step of purine methabolism, catalyzed by xanthinoxidase, which also produces superoxide. Xanthinoxidase is inhibited by allopurinol
Hyperuricaemia is a very common metabolic disorder. Elevated SUA levels occur in 2–18% of the population, varying in relationship to age, sex, and many other factors (Table (Table11).
Table 1
Most common features of trisomy 13 (the clinical signs that make up the classical triad for the recognition of Patau syndrome are marked in the table)
The SUA level reflects the net balance between its constant production and excretion. Dietary intake of urate provides a source of uric acid precursors. To maintain homeostasis, SUA is eliminated by the kidney and the gastrointestinal tract. Two thirds of the daily turnover of the urate is excreted by the kidney, where it is completely filtered at the glomerulus, completely reabsorbed in the proximal tubule, then secreted (aprox 50% of the filtered load), and finally reabsorbed.
The high SUA level can be due to an excessive production or to a decreased excretion. An increased dietary purine or fructose intake increases the SUA production. The SUA level is higher in postmenopausal women (because the uricosuric effect of estrogen) and in African Americans (3). In malignancies, polycytemia vera or haemolytic anemias, the rapid cellular turnover determines excessive SUA production. Renal insufficiency is a common cause of SUA increase. Hyperuricemia is highly prevalent in chronic kidney disease, reflecting the reducing renal excretion of SUA. The use of diuretics, by causing volume contraction, increases the SUA level by increasing urate absorbtion. The data of the recent experimental and clinical studies suggest that SUA is not only a marker of reduced kidney function, but it is also a causal factor in the development and progression of renal disease (4). ❑
Source: Europe PMC (PubMed Central)
Institution: Carol Davila University of Medicine and Pharmacy
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W46436459