Fetuin-A: A Novel Cardiovascular Risk Factor

Abstract

Fetuin-A, or α2-Heremans–Schimd glycoprotein, is a potent inhibitor of calcium-phosphate precipitation. In end-stage renal disease (ESRD) patients, its serum levels are significantly reduced favouring ectopic calcifications, such as vascular and valvular calcifications for hyperphosphatemia and increased Ca × P product. Numerous evidences indicate that in low fetuin-A levels patients, mitral and/or aortic calcifications are often present. Coronary, carotid calcifications and/or other vascular phatological findings connected with increased calcium deposition in the lamina media of the arterial wall (Monkeberg’s calcinosis or arteriosclerosis), acute inflammation and/or endothelial dysfunction can be also found. Thus, low levels of fetuin-A in ESRD act as “non-traditional” risk factor for cardiovascular disease. Other “non-traditional” cardiovascular risk factors in dialyzed patients are: extracellular volume overload; insulin resistance; anaemia, and oxidative stress, many cross-sectional studies showed a direct associations of high fetuin-A levels with impaired glucose and lipid metabolism inducing metabolic syndrome in non-dialyzed patients. In these, high fetuin-A levels induce atherosclerotic lesions by insulin resistance. In conclusion, fetuin-A is able to induce both arteriosclerosis and atherosclerosis. Its serum levels seems to act (both in dialyzed and non-dialyzed patients) such as “non-traditional” cardiovascular risk factor, even if its action mechanism was not completely elucidated and further studies performed in wide range are requested. Therapeutically, some compounds such as Sevelamer, etidronate, calcium channel blockers and others interventions, are promising in to reduce calcium deposition in the vessel walls and acute inflammation induced by the low α2-Heremans–Schmid glycoprotein serum levels in dialyzed patients. On the contrary, extended-release niacin seems to be able to reduce cardiovascular, metabolic and inflammatory complicances dependent on high fetuin-A serum levels.