Lipoprotein(a) Levels in Familial Hypercholesterolemia

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 o...

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Published in:Journal of the American College of Cardiology 2014-05, Vol.63 (19), p.1982-1989
Main Authors: Alonso, Rodrigo, MD, PhD, Andres, Eduardo, BSc, Mata, Nelva, MD, Fuentes-Jiménez, Francisco, MD, PhD, Badimón, Lina, PhD, López-Miranda, José, MD, PhD, Padró, Teresa, PhD, Muñiz, Ovidio, MD, PhD, Díaz-Díaz, Jose Luis, MD, PhD, Mauri, Marta, MD, Ordovás, Jose María, PhD, Mata, Pedro, MD, PhD
Format: Article
Language:English
Subjects:
Body mass index
Cardiology
Cardiovascular
Cardiovascular disease
Cholesterol
familial hypercholesterolemia
Heart attacks
Internal Medicine
LDL receptor mutations
lipoprotein(a)
Mutation
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Summary: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 and carrying a receptor-negative mutation in the LDLR gene compared with other less severe mutations.
ISSN:0735-1097
1558-3597
DOI:10.1016/j.jacc.2014.01.063