Testing for Lipoprotein(a) Concentration and Apolipoprotein(a) Phenotypes: Method Standardization and Pediatric Reference Values

Abstract

Increased levels of lipoprotein(a) (Lp[a])are known independent risk factor for atherosclerosis, heart disease, and stroke in adults. Even in children it could be shown that elevated levels of Lp(a) are an independent risk factor for symptomatic thromboembolism. The aim of this work was to describe the methods used for evaluating Lp(a) phenotypes, to link them to Lp(a) plasma concentrations, and to establish age-dependent reference values in children. Lp(a) plasma concentrations were measured with enzyme-linked immunosorbent assay technique in parallel to agarose gel electrophoresis and subsequent anti-apolipoprotein(a) immunoblotting. We included 184 pediatric patients with stroke or venous thromboembolism, and 150 healthy age-matched controls in this study. In the control children we could find a mean Lp(a) concentration of 3 mg/dL for children 1 to 12 months of age, and in subjects 1.2 to 18 years of age, the mean Lp(a) concentration was 10 mg/dL. Using percentile classification the upper percentile cut-offs were as follows: age 3 to 6 months: 14 mg/dL; 6.1 to 12 months: 15 mg/dL; 1.1 to 9 years: 22 mg/dL; and 9.1 to 18 years: 30 mg/dL, respectively. In the present study we have established age-dependent reference values of plasma Lp(a) concentrations. The latter will help to harmonize international pediatric studies and to further evaluate the role of elevated Lp(a) in childhood vascular disease.