LDL-unbound apolipoprotein(a) and carotid atherosclerosis in hemodialysis patients

High lipoprotein(a) [Lp(a)] plasma concentrations, which are genetically determined by apo(a) size polymorphism, are directly associated with an increased risk for atherosclerosis. Patients with end-stage renal disease (ESRD), who show an enormous prevalence of cardiovascular disease, have elevated plasma concentrations of Lp(a). In recent studies we were able to show that apo(a) size polymorphism is a better predictor for carotid atherosclerosis and coronary artery disease in hemodialysis patients than concentrations of Lp(a) and other lipoproteins. Less than 5% of apo(a) in plasma exists in a low-density lipoprotein (LDL)-unbound form. This "free" apo(a) consists mainly of disintegrated apo(a) molecules of different molecular weight, ranging from about 125 to 360 kDa. LDL-unbound apo(a) molecules are elevated in patients with ESRD. The aim of this study was therefore to investigate whether the LDL-unbound form of apo(a) contributes to the prediction of carotid atherosclerosis in a group of 153 hemodialysis patients. The absolute amount of LDL-unbound apo(a) showed a trend to increasing values with the degree of carotid atherosclerosis, but the correlation of Lp(a) plasma concentrations with atherosclerosis was more pronounced. In multivariate analysis the two variables were related to neither the presence nor the degree of atherosclerosis. Instead, the apo(a) phenotype took the place of Lp(a) and LDL-unbound apo(a). After adjustment for other variables, the odds ratio for carotid atherosclerosis in patients with a low molecular weight apo(a) phenotype was about 5 (p<0.01). This indicates a strong association between the apo(a) phenotype and the prevalence of carotid atherosclerosis. Finally, multivariate regression analysis revealed age, angina pectoris and the apo(a) phenotype as the only significant predictors of the degree of atherosclerosis in these patients. In summary, it seems that LDL-unbound apo(a) levels do not contribute to the prediction of carotid atherosclerosis in hemodialysis patients. However, this does not mean that "free", mainly disintegrated, apo(a) has no atherogenic potential.