Familial hypercholesterolaemia, not familial hypobetalipoproteinaemia, is linked to higher Lp(a) in a study of 1,153 subjects with genetically extreme LDL (Nutr Metab Cardiovasc Dis 2025)

Original title: Do genetically determined very high and very low LDL levels contribute to Lp(a) plasma concentration?

Nutr Metab Cardiovasc Dis · 28 August 2024 · 6

Giammanco A, Noto D, Nardi E, Gagliardo CM, Scrimali C, Brucato F, Spina R, Barbagallo CM, Caldarella R, Ciaccio M, Cefalù AB, Averna M

This Italian study compared Lp(a) plasma levels across 356 hypercholesterolaemic patients (212 with a causative familial hypercholesterolaemia [FH] mutation, 144 mutation-negative clinical FH), 52 with familial hypobetalipoproteinaemia type 1 (FHBL1), and 797 free-living subjects. Lp(a) was significantly higher in both FH groups (median 12.46 mg/dL and 14.0 mg/dL) than in FHBL1 or the general population (7.68 mg/dL and 7.18 mg/dL), and was similar regardless of whether the FH mutation was LDL-receptor defective or null. Subjects at high and very high cardiovascular risk had significantly higher Lp(a) (median 10.68 mg/dL and 9.20 mg/dL) than those at low or moderate risk (5.72 mg/dL and 7.80 mg/dL, p < 0.0008). The findings suggest genetically very low LDL does not lower Lp(a) in parallel, and that Lp(a) measurement in FH patients could help flag those needing earlier, more aggressive prevention.

Original abstract

Background And Aims: Lipoprotein(a) [Lp(a)] is a well-recognized risk factor for atherosclerotic cardiovascular disease (ASCVD). Few data are available on the distribution of Lp(a) levels among subjects at different cardiovascular risk and in subjects with monogenic and polygenic dyslipidemias (familial hypercholesterolemia, FH and familial hypobetalipoproteinemia type 1, FHBL1). The aim of this study was to investigate the distribution of Lp(a) plasma levels in subjects with high and low LDL-C levels (FH and FHBL1) and in the general population.

Methods And Results: The study cohorts included 356 hypercholesterolemic patients, 212 carrying a FH causative mutation, 144 with clinical FH (mutation negative - FHneg), 52 FHBL1 and 797 free-living subjects. Lp(a) levels were significantly higher in FH subjects (both FH and FHneg) (median 12.46 mg/dl and 14.0 mg/dl, respectively) compared with FHBL1 and free-living subjects (7.68 mg/dl and 7.18 mg/dl, respectively). More, Lp(a) levels were similar in FH subjects carrying LDLR defective and null mutations and FHneg. Subjects at high and very high CV risk exhibited significant higher Lp(a) levels (median 10.68 mg/dl and 9.20 mg/dl, respectively) compared with low and moderate CV risk (median 5.72 mg/dl and 7.80 mg/dl, respectively) (p < 0.0008).

Conclusions: FH subjects exhibit higher Lp(a) levels than FHBL1 and general population. Lp(a) slightly contribute to hypercholesterolemia in FH patients. Subjects at high and very high CV risk exhibited significant higher Lp(a) levels compared with low and moderate CV risk. Combined evaluation of Lp(a) levels in FH subjects with other traditional risk factors could identify very high-risk individuals who may benefit from early aggressive treatments to avoid premature CV events.

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