Ana Cenarro1, José Puzo2, Juan Ferrando3, Rocío Mateo-Gallego1, Ana M Bea1, Pilar Calmarza4, Estíbaliz Jarauta1, Fernando Civeira5. 1. Lipid Unit and Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, IIS Aragón, Universidad de Zaragoza, Zaragoza, Spain. 2. Lipid Unit, Hospital San Jorge, Huesca, Spain. 3. Lipid Unit, Hospital Royo Villanova, Zaragoza, Spain. 4. Biochemistry Department, Hospital Universitario Miguel Servet, Zaragoza, Spain. 5. Lipid Unit and Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, IIS Aragón, Universidad de Zaragoza, Zaragoza, Spain. Electronic address: civeira@unizar.es.
Abstract
BACKGROUND: Lipoprotein(a) [Lp(a)] is a lipoprotein in which apolipoproteinB-100 is linked to apolipoprotein(a) [apo(a)]. Significant variation in Lp(a) concentration is specific to LPA gene, which codes for apo(a). Nicotinic acid (NA) is used for treatment of dyslipidemias, and the lowering effect of NA on Lp(a) has been previously reported. OBJECTIVE: To evaluate the Lp(a) lowering effect of 1g/20mg and 2g/40mgday of Nicotinic acid/Laropiprant in subjects with different baseline Lp(a) concentrations and depending on the LPA genotype. METHODS: In an open-label, 10-week study, 1g/20mgday of NA/Laropiprant for 4weeks followed by 6weeks of 2g/40mgday conducted at 3 centers in Spain, 82 subjects were enrolled. Patients were studied at baseline and at the end of both treatment periods and were enrolled in three groups: normal Lp(a) (<50mg/dL), high Lp(a) (50-120mg/dL) and very high Lp(a) (>120mg/dL). The LPA genetic polymorphism was analyzed by a real-time PCR. RESULTS: There was a significant difference in LPA genotypes among Lp(a) concentration groups and an inverse and significant correlation between baseline Lp(a) concentration and LPA genotype was found (R=-0.372, p<0.001). There were a significant decrease in total cholesterol, triglycerides, LDL cholesterol, apo B and Lp(a), and a significant increase in HDL cholesterol after NA/Laropiprant treatment, without changes in BMI. However, there were no statistical differences in percentage variation of analyzed variables depending on LPA genotype. CONCLUSION: LPA genotype is a major determinant of Lp(a) baseline concentration. However, the lipid lowering effect of NA is not related to LPA genotype.
BACKGROUND:Lipoprotein(a) [Lp(a)] is a lipoprotein in which apolipoproteinB-100 is linked to apolipoprotein(a) [apo(a)]. Significant variation in Lp(a) concentration is specific to LPA gene, which codes for apo(a). Nicotinic acid (NA) is used for treatment of dyslipidemias, and the lowering effect of NA on Lp(a) has been previously reported. OBJECTIVE: To evaluate the Lp(a) lowering effect of 1g/20mg and 2g/40mgday of Nicotinic acid/Laropiprant in subjects with different baseline Lp(a) concentrations and depending on the LPA genotype. METHODS: In an open-label, 10-week study, 1g/20mgday of NA/Laropiprant for 4weeks followed by 6weeks of 2g/40mgday conducted at 3 centers in Spain, 82 subjects were enrolled. Patients were studied at baseline and at the end of both treatment periods and were enrolled in three groups: normal Lp(a) (<50mg/dL), high Lp(a) (50-120mg/dL) and very high Lp(a) (>120mg/dL). The LPA genetic polymorphism was analyzed by a real-time PCR. RESULTS: There was a significant difference in LPA genotypes among Lp(a) concentration groups and an inverse and significant correlation between baseline Lp(a) concentration and LPA genotype was found (R=-0.372, p<0.001). There were a significant decrease in total cholesterol, triglycerides, LDL cholesterol, apo B and Lp(a), and a significant increase in HDL cholesterol after NA/Laropiprant treatment, without changes in BMI. However, there were no statistical differences in percentage variation of analyzed variables depending on LPA genotype. CONCLUSION: LPA genotype is a major determinant of Lp(a) baseline concentration. However, the lipid lowering effect of NA is not related to LPA genotype.
Authors: Yansheng Liu; Alfonso Buil; Ben C Collins; Ludovic C J Gillet; Lorenz C Blum; Lin-Yang Cheng; Olga Vitek; Jeppe Mouritsen; Genevieve Lachance; Tim D Spector; Emmanouil T Dermitzakis; Ruedi Aebersold Journal: Mol Syst Biol Date: 2015-02-04 Impact factor: 11.429
Authors: Lotte C A Stiekema; Koen H M Prange; Renate M Hoogeveen; Simone L Verweij; Jeffrey Kroon; Johan G Schnitzler; Kim E Dzobo; Arjen J Cupido; Sotirios Tsimikas; Erik S G Stroes; Menno P J de Winther; Mahnoush Bahjat Journal: Eur Heart J Date: 2020-06-21 Impact factor: 35.855