Lipoprotein apheresis lowers macrophage cholesterol-loading capacity alongside Lp(a), an Italian case-control study of 34 patients with two novel LPA variants (J Clin Lipidol 2020)

Original title: Lipoprotein(a) concentration, genetic variants, apo(a) isoform size, and cellular cholesterol efflux in patients with elevated Lp(a) and coronary heart disease submitted or not to lipoprotein apheresis: An Italian case-control multicenter study on Lp(a)

J Clin Lipidol · 1 January 2020 · 6

Stefanutti C, Pisciotta L, Favari E, Di Giacomo S, Vacondio F, Zenti MG, Morozzi C, Berretti D, Mesce D, Vitale M, Pasta A, Ronca A et al.

This Italian multicenter case-control study examined the relationship between Lp(a), apo(a) isoform size and cellular cholesterol loading capacity (CLC) in patients with elevated Lp(a) and premature coronary artery disease, comparing 18 patients receiving lipoprotein apheresis (LA) with 16 not receiving it. Mean macrophage CLC before apheresis was higher than in normolipidaemic controls (19.7±0.9 vs 16.01±0.98 μg/mg protein), and fell after apheresis to 16.1±0.8 μg/mg protein (P=.003), comparable to controls; CLC correlated with Lp(a) plasma concentration (P=.035). Apheresis did not significantly change apo(a) isoform size distribution. Genetic profiling identified two novel LPA gene variants (exon 21 c.3269C>G p.Pro1090Arg, and rs41259144 c.2969G>A p.Arg990Gln) alongside known common variants, though genetic assessment did not predict coronary disease risk in these patients. The findings show lipoprotein apheresis reduces both serum Lp(a) and macrophage cholesterol loading capacity.

Original abstract

Background: Coronary artery disease (CAD) risk is greater with higher plasma lipoprotein(a)[Lp(a)] concentrations or smaller apoisoform size and putatively with increased cellular cholesterol loading capacity (CLC). The relationship between Lp(a) and CLC is not known. Information on Lp(a) polymorphisms in Italian patients is lacking.

Objective: The objective of this study was to determine relationships between Lp(a) and CLC, the impact of lipoprotein apheresis (LA), and describe the genetic profile of Lp(a).

Methods: We conducted a multicenter, observational study in Italian patients with hyperLp(a) and premature CAD with (n = 18)/without (n = 16) LA in which blood samples were analyzed for Lp(a) parameter and CLC. Genetic profiling of LPA was conducted in patient receiving LA.

Results: Mean macrophage CLC of the pre-LA serum was significantly higher than that of normolipidemic controls (19.7 ± 0.9 μg/mg vs 16.01 ± 0.98 μg/mg of protein, respectively). After LA, serum macrophage CLC was markedly lower relative to preapheresis (16.1 ± 0.8 μg/mg protein; P = .003) and comparable with CLC of the normolipidemic serum. LA did not significantly affect average apo(a) isoform size distribution. No anthropometric or lipid parameters studied were related to serum CLC, but there was a relationship between CLC and the Lp(a) plasma concentration (P = .035). DNA analysis revealed a range of common genetic variants. Two rare, new variants were identified: LPA exon 21, c.3269C>G, p.Pro1090Arg, and rs41259144 p.Arg990Gln, c.2969G>A CONCLUSIONS: LA reduces serum Lp(a) and also reduces macrophage CLC. Novel genetic variants of the LPA gene were identified, and geographic variations were noted. The complexity of these polymorphisms means that genetic assessment is not a predictor of CAD risk in hyperLp(a).

Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.