ATHEROGENESIS AND CARDIAC DEATH - ARE THEY RELATED TO DIALYSIS PROCEDURE AND BIOCOMPATIBILITY

Cardiac events are a major cause of death in dialysed patients. This i s due, at least in part, to the high prevalence of atherosclerotic cor onary heart disease. To a large extent, however, coronary lesions are acquired in the predialytic phase of chronic renal failure. The suscep tibility of the heart to ischaemia is modulated by a number of factors , e.g. microvascular abnormalities, increased cardiac pulsatile worklo ad, disturbed cardiac glucose metabolism, imbalanced autonomic innerva tion. The paradoxical result of there being no relationship of cardiac death in dialysis patients to blood pressure may be explained by conf ounding factors. Intradialytic hypotension appears to be an independen t risk factor. The dialysis patient is exposed to hypertension and dys lipidaemia, two potent risk factors of atherosclerosis. Although no de finite information is available, it is conceivable that factors relate d to dialysis procedures may also influence early or late events in at herogenesis. Such potential factors include oxidative modification of lipids, modulation of insulin resistance or glucose metabolism by non- insulin-dependent pathways, expression of adhesion molecules and activ ation of potential effector cells in atherogenesis, particularly monoc ytes and platelets, changes of synthesis and/or response to endothelin and nitroxide (EDRF), and possibly also accelerated formation of adva nced plaques by hyperphosphataemia and/or hyperparathyroidism. Such pr oatherogenic mechanisms must be balanced against factors potentially p rotecting against atherogenesis; these comprise altered arachidonic ac id metabolism (increased prostacyclin and decreased thromboxane synthe sis), impaired platelet aggregation, antiatherosclerotic effects of he parin, and diminished concentrations of 1,25(OH)2D3, i.e. of a proathe rogenic compound.