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ARS Home » Northeast Area » Boston, Massachusetts » Research » Publications at this Location » Publication #307509
Title: Lipoprotein(a) levels in familial hipercholesterolaemia: an important predictor for cardiovascular disease independent of the type of LDL-receptor mutation

Author
item ALONSO, RODRIGO - Iis-Fundacion Jimenez Diaz
item ANDRES, EDUARDO - Spanish National Cancer Research Centre
item MATA, NELVA - Madrid Health Authority And Fundacion
item FUENTES-JIMENEZ, FRANCISCO - Reina Sofia University
item BADIMON, LINA - Catalan Institute Of Health
item LOPEZ-MIRANDA, JOSE - Reina Sofia University
item PADRO, TERESA - Catalan Institute Of Health
item MUNIZ, OVIDIO - Virgen Del Rocio University Hospital
item DIAZ-DIAZ, JOSE LUIS - Hospital Abente Y Lago
item MAURI, MARTA - Hospital Terrace
item ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item MATA, PEDRO - Familial Hypercholesterolemia Foundation

Submitted to: American Journal of Ophthalmology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/20/2014
Publication Date: 5/1/2014
Citation: Alonso, R., Andres, E., Mata, N., Fuentes-Jimenez, F., Badimon, L., Lopez-Miranda, J., Padro, T., Muniz, O., Diaz-Diaz, J., Mauri, M., Ordovas, J.M., Mata, P. 2014. Lipoprotein(a) levels in familial hipercholesterolaemia: an important predictor for cardiovascular disease independent of the type of LDL-receptor mutation. American Journal of Opthalmology. 63(19):1982-1989.

Interpretive Summary: Circulating blood lipid levels have been associated with cardiovascular disease (CVD) risk. Most of the research has focused on the lipid fractions known as bad cholesterol (LDL-C) and good cholesterol (HDL-C). However, other plasma lipoproteins may be of great relevance to further refine the individual risk. One of them is known as lipoprotein(a) [Lp(a)]. The aim of this study was to determine the relationship between Lp(a) and cardiovascular disease (CVD) in a unique cohort of people with heterozygous familial hypercholesterolemia (FH). These people are at very high risk of CVD resulting from extremely high LDL-C levels due to genetic mutations in the LDL receptor gene. We carried out a cross-sectional analysis of 1,960 patients with FH and 957 non-FH relatives recruited for a long-term observational cohort study of a molecularly well-defined FH study group. We measured Lp(a) concentrations in blood. Our analyses reveal that patients with FH, especially those with CVD, had higher Lp(a) plasma levels compared with their unaffected relatives. Moreover, a significant difference in Lp(a) levels was observed when the most frequent null and defective mutations in LDLR mutations were analyzed. More refined analyses showed that Lp(a) was an independent predictor of cardiovascular disease. Thus, 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. In summary, our study shows that 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.

Technical Abstract: To determine the relationship between lipoprotein(a) [Lp(a)] and cardiovascular disease (CVD) in a large cohort of heterozygous familial hypercholesterolemia (FH) patients. Lipoprotein(a) is considered a cardiovascular risk factor. Nevertheless, the role of Lp(a) as a predictor of CVD in FH has been a controversial issue. Cross-sectional analysis of 1960 FH and 957 non-FH relatives recruited at SAFEHEART, a long-term observational cohort study of a molecularly well-defined FH population. Lipoprotein(a) concentrations were measured in plasma using an immunoturbidimetric method. 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 analysed (p<0.0016). In multivariate analysis, Lp(a) was an independent predictor for 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) < 50 mg/dL. Lipoprotein(a) is an independent predictor of CVD in men and women with FH. Cardiovascular risk is higher in those patients with lipoprotein(a) > 50 mg/dL carrying a receptor-negative mutation in LDLR gene compared with other less severe mutations.