Further characterization of the plasma lipoprotein(a) distribution

The plasma lipoprotein(a) [Lp(a)] distribution in caucasians is heavily skewed to the right, with evidence of bimodality. As there is a well-described inverse relationship between apolipoprotein(a) [apo(a)] size and Lp(a) concentration, it is likely that the presence of multiple apo(a) isoforms of differing frequency has a significant impact on the final distribution of Lp(a) concentrations. We have previously described an immunoblot method for examining the relationship between apolipoprotein(a) [apo(a)] size and lipoprotein(a) [Lp(a)] mass among samples heterozygous for apo(a) size, thus eliminating confounding by null or undetected apo(a) isoforms. In the present study, this method has been applied to examine the plasma Lp(a) distribution, independent of the effects of apo(a) isoform size and frequency. Seventy subjects heterozygous for apo(a) size were studied. To take into account the inverse relationship (P <0.001) between apo(a) isoform size and Lp(a) concentration, Lp(a) data associated with each apo(a) isoform were normalized as multiples of the median Lp(a) concentration for that isoform. These apo(a) isoform-independent Lp(a) data demonstrated a strikingly multimodal distribution, with five major peaks. The relative frequencies of Lp(a) peaks 1–5 were 17.1%, 15.0%, 35.7%, 23.6%, and 8.6%, and associated median Lp(a) concentrations were 1.0, 6.2,15.0, 21.8, and 39.6 mg/dL, respectively. Multivariate analysis demonstrated that apo(a) isoform size accounted for 23% and isoform-independent Lp(a) peaks for 59.5% of the variation in Lp(a) concentration. Further investigation of the characteristics of the apo(a) isoform-independent Lp(a) distribution is warranted.     

Low-density lipoprotein metabolism and its association to plasma lipoprotein(a) in the nephrotic syndrome

Patients with nephrotic syndrome have multiple abnormalities of lipoprotein metabolism, but the cause and exact nature of these abnormalities have not been established. In the present study we have determined the kinetics of plasma low-density lipoprotein (LDL) apoB in seven nephrotic patients demonstrating an elevated LDL apoB production rate (25.7 ± 6.4 vs. 13.1 ± 0.3 mg kg^–1 day^–1; P  < 0.001) but a normal LDL apoB fractional catabolic rate (FCR) (0.31 ± 0.04 vs. 0.33 ± 0.008 pools day^–1; NS) compared with 41 healthy control subjects. However, two out of the seven patients had a markedly low LDL apoB-FCR. Serum albumin was inversely correlated with the LDL apoB production rate ( R  = –0.82; P  < 0.05). Plasma lipoprotien (a) [Lp(a)] levels were significantly ( P  < 0.001) increased in the nephrotic patients compared with control subjects. Significant correlations were observed between log Lp(a) and LDL apoB production rate ( R  = 0.90; P  < 0.01), VLDL-cholesterol ( R  = 0.95; P  < 0.001) and VLDL-triglycerides ( R  = 0.80; P  < 0.05) respectively. In summary, the present study suggests that nephrotic hyperlipidaemia may be caused by at least two independent mechanisms. The elevated LDL apoB production rate is highly correlated with the prevailing levels of serum albumin, whereas some nephrotic patients seem to have a decreased LDL apoB clearance, suggesting impaired LDL receptor-mediated clearance. The present results also suggest that the elevated plasma Lp(a) levels in nephrosis are related to an increased hepatic synthesis rather than a decreased catabolism of lipoproteins.     

Free cholesterol distribution during in vitro lipolysis of rat plasma very low density lipoprotein: lack of a role for blood and heart cells

Abstract. In the present study, an attempt was made to quantify free cholesterol transfer from lipolyzed VLDL to HDL, blood cells and heart cells. The experiments were carried out in vitro or in the isolated perfused rat heart with rat plasma VLDL labelled biosynthetically with [¹⁴C]-palmitic acid and [³H]cholesterol, and with bovine milk lipoprotein lipase, human blood cells (erythrocytes, leucocytes and platelets) or rat plasma HDL. Exchange and transfer of free cholesterol was followed by radioactivity and specific activity determinations. The study demonstrated an exchange of free cholesterol between VLDL and blood cells (6–10 h) and VLDL and HDL (120 min). However, none of the blood cells tested served as acceptor for lipolysis-generated free cholesterol, whereas HDL did. In the isolated perfused rat heart, a maximum of 25% of the free cholesterol radioactivity lost from VLDL was found in the tissue. Since exchange must have contributed to this process, the transfer of free cholesterol molecules to the heart is necessarily lower. The study thus demonstrated minimal or possibly no net transport of free cholesterol from VLDL to cells and cell membranes.     

Quantification of lipoprotein(a) in dried blood spots and screening for above-normal lipoprotein(a) concentrations in newborns

Lipoprotein(a) [Lp(a)] is considered an additional, independent, and largely genetically determined risk factor for the development of premature coronary heart disease. Analogous with increased Lp(a) concentrations that represent an additional risk factor in adults, above-normal concentrations of Lp(a) can be detected in five- to seven-day-old newborns. We describe a simple enzyme-linked immunosorbent assay for measuring Lp(a) in dried blood spots collected by heel-prick in five- to seven-day-old infants. Lp(a) could be quantitatively recovered from blood spots. We chose a cutoff value of 100 mg/L for identifying the newborns at risk, based on the Lp(a) distribution in 180 such infants.