Calcification and Cardiovascular Health

Abstract

Remic cardiovascular disease is characterized by acceler- ated calcifying atherosclerosis and valvular heart disease. Vascular calcification develops at 2 different sites within the vessel wall. Although intimal plaque calcification is a feature of genuine atherosclerosis, medial calcification is restricted to the smooth muscle cell layer and especially to the elastic laminae of arterial vessels (Figure 1). Both entities can be frequently observed in chronic kidney disease (CKD) patients. Dialysis patients with intimal calcifications are elderly and characterized by a history of "traditional" risk factors (eg, smoking and dyslipidemia) before the start of dialysis, whereas those with medial calcifications are, on average, 20 years younger and characterized by a longer time on dialysis treatment and a higher incidence of derangements in their calcium (Ca)phosphate (P) balance. 1 Another recent study in incident dialysis patients showed that those with rapid arterial calcification progress already had calcified coronary arteries before reaching the dialysis stage.2 This emphasizes that diagnostic, preventive, and therapeutic measures need to be initiated in early CKD stages. The clinical importance of this notion is stressed by a number of reports demonstrating that coronary artery and valvular calcifi- cations occur prematurely and are very prevalent in dialysis patients and that they are independent risk factors of cardiovas- cular death in this patient group. 1,3-7 Such calcifications can, therefore, serve to at least partially explain why cardiovascular mortality is dramatically increased in the uremic as compared with a normal population and why it is not appropriately explained by the traditional Framingham risk factors. 8 One of the mechanisms by which medial vascular calcification feeds into cardiovascular mortality may be via the associated increase in aortic pulse wave velocity.9,10 Calcified arteries become stiffer, causing quicker return of the systolic pulse wave from the periphery, thereby increasing left ventricular afterload. Through this mechanism, a high aortic pulse wave velocity is associated with increased left ventricular mass. Based on registry data and cross-sectional analyses, an in- creased CaP product because of hyperphosphatemia and/or hypercalcemia (derived from a positive Ca balance, eg, Ca- containing P binders) is thought to be a key determinant of cardiovascular mortality and progression factors of unwanted calcifications in uremia. 4,11,12 In 2 studies focusing on young dialysis patients with childhood-onset renal disease, coronary artery calcifications (quantified by electron-beam computed tomography) were highly prevalent in the age group of 20- to 40-year-old patients and associated with an increased CaP