Cascade testing for elevated lipoprotein(a) in relatives of probands with familial hypercholesterolaemia and elevated lipoprotein(a)

Abstract Background and aims Familial hypercholesterolaemia (FH) and elevated plasma lipoprotein(a) [Lp(a)] are inherited conditions independently associated with atherosclerotic cardiovascular disease. This study investigated the detection of new cases of elevated Lp(a) during cascade testing of relatives of probands with a definite diagnosis of FH and elevated Lp(a) (≥50 mg/dL). Methods Relatives from 62 adult probands were tested for FH genetically and for elevated Lp(a) using an immunoassay. The prevalence and yield of new cases of FH with or without elevated Lp(a) (≥50 mg/dL) among relatives and the association between the detection of elevated Lp(a) and the Lp(a) concentration of the probands were assessed. Results Among 162 relatives tested (136 adults and 26 children), the prevalence of FH and elevated Lp(a) was 60.5% and 41.4%, respectively: FH alone was detected in 31.5%, elevated Lp(a) alone in 12.3%, FH with elevated Lp(a) in 29.0%, and neither disorder in 27.2% of the relatives. Cascade testing detected a new case of FH, elevated Lp(a) and FH with elevated Lp(a) for every 1.5, 2.1 and 3.0 relatives tested, respectively. The proportion of relatives detected with elevated Lp(a) was significantly higher when tested from probands with Lp(a) ≥100 mg/dL compared with those from probands with Lp(a) between 50-99 mg/dL (53% vs 34%, p = 0.018). The concordance between the detection of FH and elevated Lp(a) was 56.2% (kappa statistic 0.154), indicating a poor agreement. Conclusions A dual approach to cascade testing families for FH and high Lp(a) from appropriate probands can effectively identify not only new cases of FH, but also new cases of elevated Lp(a) with or without FH. The findings accord with the co-dominant and independent heritability of FH and Lp(a).