Lp(a) predicts cardiovascular disease in familial hypercholesterolaemia independent of the LDLR mutation: SAFEHEART (Alonso et al., JACC 2014)

Original title: Lipoprotein(a) levels in familial hypercholesterolemia: an important predictor of cardiovascular disease independent of the type of LDL receptor mutation

J Am Coll Cardiol · 20 May 2014 · 7

Alonso R, Andres E, Mata N, Fuentes-Jiménez F, Badimón L, López-Miranda J, Padró T, Muñiz O, Díaz-Díaz JL, Mauri M, Ordovás JM, Mata P et al.

In 1,960 patients with molecularly defined heterozygous FH and 957 unaffected relatives, Lp(a) was higher in FH, higher still in FH with cardiovascular disease, and an independent predictor of events; patients with receptor-null LDLR mutations and Lp(a) above 50 mg/dL had the highest risk. The evidence base for measuring Lp(a) in every FH patient.

Original abstract

Objectives: The aim of this study was to determine the relationship between lipoprotein(a) [Lp(a)] and cardiovascular disease (CVD) in a large cohort of patients with heterozygous familial hypercholesterolemia (FH).

Background: Lp(a) is considered a cardiovascular risk factor. Nevertheless, the role of Lp(a) as a predictor of CVD in patients with FH has been a controversial issue.

Methods: A cross-sectional analysis of 1,960 patients with FH and 957 non-FH relatives recruited for SAFEHEART (Spanish Familial Hypercholesterolemia Cohort Study), a long-term observational cohort study of a molecularly well-defined FH study group, was performed. Lp(a) concentrations were measured in plasma using an immunoturbidimetric method.

Results: Patients with FH, especially those with CVD, had higher Lp(a) plasma levels compared with their unaffected relatives (p < 0.001). A significant difference in Lp(a) levels was observed when the most frequent null and defective mutations in LDLR mutations were analyzed (p < 0.0016). On multivariate analysis, Lp(a) was an independent predictor of cardiovascular disease. Patients carrying null mutations and Lp(a) levels >50 mg/dl showed the highest cardiovascular risk compared with patients carrying the same mutations and Lp(a) levels <50 mg/dl.

Conclusions: Lp(a) is an independent predictor of CVD in men and women with FH. The risk of CVD is higher in those patients with an Lp(a) level >50 mg/dl and carrying a receptor-negative mutation in the LDLR gene compared with other less severe mutations.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.