Individuals with familial hypercholesterolemia and cardiovascular events have higher circulating Lp(a) levels
| Autor: | Kristina Bjorkman, Joakim Sandstedt, Stefano Romeo, Claudia Tarlarini, Rosellina Margherita Mancina, Chiara Pavanello, Laura Calabresi, Lorena Mosca, Carlo Pirazzi |
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| Rok vydání: | 2018 |
| Předmět: |
Oncology
Adult Male medicine.medical_specialty Endocrinology Diabetes and Metabolism Nonsense mutation Mutation Missense Familial hypercholesterolemia Disease 030204 cardiovascular system & hematology Cohort Studies Hyperlipoproteinemia Type II 03 medical and health sciences 0302 clinical medicine Internal medicine Internal Medicine medicine Humans 030212 general & internal medicine Risk factor Hypolipidemic Agents Nutrition and Dietetics medicine.diagnostic_test business.industry Genetic disorder Middle Aged medicine.disease Codon Nonsense Cohort Female Cardiology and Cardiovascular Medicine Lipid profile business Lipoprotein Lipoprotein(a) |
| Zdroj: | Journal of clinical lipidology. 13(5) |
| ISSN: | 1933-2874 |
| Popis: | Background Cardiovascular disease (CVD) is a major cause of mortality and morbidity. Increased low-density lipoprotein cholesterol (LDL-C) level is its major risk factor. Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated LDL-C since birth and subsequent premature CVD. There is a heterogeneity in the CVD onset in patients with FH. This is potentially due to the presence of other independent risk factors. Lipoprotein(a) [Lp(a)] is an LDL-like particle and represents a strong risk factor for CVD. Objective Our objective was to understand the contribution of Lp(a) in the susceptibility to CVD in individuals with genetic diagnosis of FH. Methods We measured Lp(a) levels in 2 independent and well-characterized genetic-FH cohorts: the FH-Gothenburg cohort (n = 190) and the FH-CEGP Milan cohort (n = 160). The genetic diagnosis was performed by targeted next-generation sequencing (FH-Gothenburg and part of the FH-CEGP Milan cohort), or by Sanger sequencing. Results We show that among individuals with genetic diagnosis of FH, those with previous CVD had higher Lp(a) levels. In addition, analyzing the response to the lipid-lowering therapies, we have also shown that statins had the same LDL-C–lowering effect irrespective of the type of FH-causative mutation. However, when we examined the lipid-lowering effect of proprotein convertase subtilisin/kexin type 9 inhibition by antibodies, we observed a trend in a better reduction of the LDL-C level in carriers of nonsense mutations. Conclusion In conclusion, our results suggest that Lp(a) contributes to CVD onset in individuals with genetic diagnosis of FH. Our finding supports the importance to identify an efficacious therapy to lower Lp(a) in patients with FH to prevent CVD onset or recurrence. |
| Databáze: | OpenAIRE |
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