title: Lipoprotein(a) levels in familial hypercholesterolemia: an important predictor of cardiovascular disease independent of the type of LDL receptor mutation.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Internal Medicine, IIS-Fundación Jiménez Díaz, Madrid, Spain. Electronic address: ralonso@fjd.es.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Alonso
authors.affiliation: Bioinformatic Unit, Spanish National Cancer Research, Madrid, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Andres
authors.affiliation: Department of Epidemiology, Madrid Health Authority, Madrid, Spain.
authors.forename: Nelva
authors.initials: N
authors.lastname: Mata
authors.affiliation: Department of Internal Medicine, Instituto Maimonides de Investigación Biomédica de Córdoba/Hospital Universitario Reina Sofía, Córdoba, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Fuentes-Jiménez
authors.affiliation: Instituto Catalán Ciencias Cardiovasculares, IIB-Sant Pau, Barcelona, Spain.
authors.forename: Lina
authors.initials: L
authors.lastname: Badimón
authors.affiliation: Department of Internal Medicine, Instituto Maimonides de Investigación Biomédica de Córdoba/Hospital Universitario Reina Sofía, Córdoba, Spain.
authors.forename: José
authors.initials: J
authors.lastname: López-Miranda
authors.affiliation: Instituto Catalán Ciencias Cardiovasculares, IIB-Sant Pau, Barcelona, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Padró
authors.affiliation: Department of Internal Medicine, Hospital Virgen del Rocío, Sevilla, Spain.
authors.forename: Ovidio
authors.initials: O
authors.lastname: Muñiz
authors.affiliation: Department of Internal Medicine, Hospital Abente y Lago, A Coruña, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Díaz-Díaz
authors.affiliation: Department of Internal Medicine, Hospital de Terrassa, Terrassa, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Mauri
authors.affiliation: Nutrition and Genomics Laboratory, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts.
authors.forename: Jose María
authors.initials: JM
authors.lastname: Ordovás
authors.affiliation: Fundación Hipercolesterolemia Familiar, Madrid, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Mata
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D017270:Lipoprotein(a) / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011237:Predictive Value of Tests; D011973:Receptors, LDL / Q000097:blood / Q000235:genetics*
chemical_list: D015415:Biomarkers; D017270:Lipoprotein(a); D011973:Receptors, LDL
keywords: LDL receptor mutations; cardiovascular disease; familial hypercholesterolemia; lipoprotein(a)