Cardiovascular calcifications in uremic patients: clinical impact on cardiovascular function

Cardiovascular disease is the leading cause of mortality among patients with ESRD (chronic kidney disease stage 5). Left ventricular hypertrophy and arterial diseases are the two principal risk factors for cardiovascular mortality in hemodialysis patients. Epidemiologic studies show that damage to large conduit arteries contributes to morbidity and mortality in patients with chronic kidney disease. Atherosclerosis is primarily an intimal disease characterized by the presence of plaques and occlusive lesions. Although atherosclerosis is the most frequent underlying cause of cardiovascular disease in patients with ESRD, it represents only one form of structural response to metabolic and hemodynamic alterations that interfere with the process of aging. Arterial alterations in ESRD include nonocclusive arterial remodeling accompanying the growing hemodynamic burden and humoral abnormalities that are associated with chronic uremia. The consequences of these alterations are different from those attributed to atherosclerotic plaques and are characterized principally by hardening (stiffening) of arteries. Arteriosclerosis, characterized by stiffening of the aorta and large capacitative arteries, is a major determinant of left ventricular pressure overload and of abnormal coronary perfusion. Atherosclerosis and arteriosclerosis are frequently comorbid and characterized by a high degree of both intimal and medial calcifications in patients with ESRD. The extent of calcifications and the degree of arterial stiffening are independent predictors of mortality. Studies in patients with ESRD have shown that attenuation of arterial stiffness can have a favorable effect, associated with regression of left ventricular hypertrophy, on survival. Calcium-free, metal-free phosphate binders such as sevelamer can reduce calcification scores.