Rodrigo Alonso1, Eduardo Andres2, Nelva Mata3, Francisco Fuentes-Jiménez4, Lina Badimón5, José López-Miranda4, Teresa Padró5, Ovidio Muñiz6, Jose Luis Díaz-Díaz7, Marta Mauri8, Jose María Ordovás9, Pedro Mata10. 1. Department of Internal Medicine, IIS-Fundación Jiménez Díaz, Madrid, Spain. Electronic address: ralonso@fjd.es. 2. Bioinformatic Unit, Spanish National Cancer Research, Madrid, Spain. 3. Department of Epidemiology, Madrid Health Authority, Madrid, Spain. 4. Department of Internal Medicine, Instituto Maimonides de Investigación Biomédica de Córdoba/Hospital Universitario Reina Sofía, Córdoba, Spain. 5. Instituto Catalán Ciencias Cardiovasculares, IIB-Sant Pau, Barcelona, Spain. 6. Department of Internal Medicine, Hospital Virgen del Rocío, Sevilla, Spain. 7. Department of Internal Medicine, Hospital Abente y Lago, A Coruña, Spain. 8. Department of Internal Medicine, Hospital de Terrassa, Terrassa, Spain. 9. Nutrition and Genomics Laboratory, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts. 10. Fundación Hipercolesterolemia Familiar, Madrid, Spain.
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.
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.
Authors: Patrick M Moriarty; Stephen A Varvel; Philip L S M Gordts; Joseph P McConnell; Sotirios Tsimikas Journal: Arterioscler Thromb Vasc Biol Date: 2017-01-05 Impact factor: 8.311