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Is there a role for niacin in familial hypercholesterolaemia?
Abstracts / Atherosclerosis 241 (2015) e72ee148
EAS-0874. GENETIC ASSOCIATION OF SINGLE NUCLEOTIDE POLYMORPHISMS OF ABCA1, APOA1 AND LCAT GENES IN SUBJECTS WITH LOW CONCENTRATION OF HIGH DENSITY LIPOPROTEIN-CHOLESTEROL
e109
Conclusions: In a population of dyslipidemic patients, only lipid levels but not statin treatment correlates to Lp-PLA2 levels.
Familial hypercholesterolaemia F.H. Sakri 1, N.A. Mohd Mokhsin 1, W.N.H. Wan Ahmad 1, T. Abdul Rahman 1, B.P. Hoh 2, H. Mohd Nawawi 1, *. 1 Centre for Pathology Diagnostic and Research Laboratories, Faculty of Medicine Universiti Teknologi Mara, Sungai Buloh, Malaysia; 2 Institute of Medical Molecular Biotechnology, Faculty of Medicine Universiti Teknologi Mara, Sungai Buloh, Malaysia
* Corresponding author. Aim: Coronary artery disease (CAD) is the major cause of death in the developing world, including Malaysia. It has been well established that high density lipoprotein cholesterol (HDL-c) concentration is inversely correlated with risk of CAD. Molecular defects that lead to HDL-c deficiency have been identified in several candidate genes including ATPebinding cassette transporter A1 (ABCA1), Apolipoprotein A1 (APOA1) and Lecithin cholesterol acyltransferase (LCAT). Using a “power extreme” approach, this study attempts to investigate the genetic association of three candidate genes namely ABCA1, APOA1 and LCAT among 70 Malaysian subjects with low concentration of HDL-c. Methods: Candidate genes ABCA1, APOA1 and LCAT were amplified by polymerase chain reaction (PCR) and sequenced in 210 subjects of whom 70 had low HDL-c concentration (HDL-c 0.6 mmol/L and HDL-c 0.7 mmol/L). Results: ABCA1 (rs4149337 and rs2066881) and APOA1 (rs12718465, rs2070665, rs5072 and rs7116797) variants were significantly associated with low concentration of HDL-c (p <0.05). LCAT however was not associated with the HDL-c concentration in the studied subjects. Conclusion: Our study confirms that genetic variations of ABCA1 and APOA1 play an important role in HDL-c deficiency amongst Malaysians.
Lp-PLA2 EAS-0148. LP-PLA2 LEVELS ARE INDEPENDANT OF STATIN TREATMENT IN DYSLIPIDEMIC PATIENTS D. Rosenbaum 1, *, A. mattina 1, R. bittar 2, E. bruckert 3, D. bonnefont e-Salp^ etri ere, rousselot 2, P. giral 3. 1 Cardiovascular Prevention, GH Piti e-Salp^ etri ere, Paris, France; Paris, France; 2 Lipid Biochemistry, GH Piti 3 Cardiovascular Prevention Unit, GH Piti e-Salp^ etri ere, Paris, France
* Corresponding author. Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory biomarker transported by the LDL particles that has been lnked to cardiovascular events independently of LDL-C levels and traditional cardiovascular risk factors. Statins diminishes cardiovascular risk, LDL-C and therefore LpPLA2. The aim of this study was to study the determinants of Lp-PLA2 in a population of treated and untreated dyslipidemic patients in primary prevention. Methods: All patients recruited at our outpatient clinic underwent routine clinical and biological assessments. Lp-PLA2 activity was measured using an automated colorimetric method using a rate reaction assay with 1myristoyl-2-(4-nitrophenylsuccinyl) phosphatidylcholine as a substrate (Diadexus Inc; Eurobio, France). Results: 259 patients were included with 50% under statin. Mean age was 57±13 years. Lp-PLA2 levels ranged from 60 to 381 nmol/mL/min with a mean of 168±47 ng/mL. 137 patients presented with hypertension and 55 had treatment for diabetes.. In univariate analysis, we found a strong positive correlation between Lp-PLA2, LDL-C (r¼0.57 p<0.0001) and negative with HDL-C (r¼0.26 p<0.0001) but no association with other risk factors. Moreover, Lp-PLA2 was higher in smokers. In statin-treated patients, LDL-C but not HDL-C correlated to Lp-PLA2. Multivariate analysis showed that age, LDL-C, HDL-C, and gender independently determined Lp-PLA2 but not smoking, diabetes, body mass index, blood pressures or statin treatment.
EAS-0162. IS THERE A ROLE FOR NIACIN IN FAMILIAL HYPERCHOLESTEROLAEMIA? M. Hu 1, Y.L. Yang 1, D. Masuda 2, S. Yamashita 2, B. Tomlinson 1, *. 1 Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong, China; 2 Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
* Corresponding author. Aim: Recent studies with extended release (ER) niacin in patients receiving intensive statin treatment with very low levels of low-density lipoprotein cholesterol (LDL-C) showed no benefit. In HPS2-THRIVE there was a trend for better outcomes in subgroups with higher baseline LDL-C or apolipoprotein (apo) B. We compared the lipid responses to ER niacin/ laropiprant in Chinese patients with and without familial hypercholesterolaemia (FH) to identify if those with higher baseline LDL-C might benefit. Methods: Lipid responses were compared in patients with FH (n¼30, 28 on statins) or those with other dyslipidaemias (n¼91, 38 on statins) treated with ER niacin/laropiprant combination 1000/20 mg for 4 weeks and then 2000/40 mg for 8 weeks. Results: FH patients had higher (P<0.05) baseline levels of LDL-C (3.56±0.86 mmol/L vs. 3.07±0.92 mmol/L) and had greater reductions (P<0.05) in LDL-C (-30.9±17.0% vs. -16.1±27.7%), non-high-density lipoprotein cholesterol (-32.0±17.4% vs. -22.3±18.8%) and apo B (-27.8±14.2% vs. -20.7±15.1%) than those without FH. Seven patients with FH (23%) had reductions in LDL-C of 50-60% after treatment with niacin. Multivariate regression analysis showed that patients with higher baseline LDL-C and those receiving statins had greater LDL-C reductions. Conclusion: Patients with FH had greater reductions in LDL-C with ER niacin/laropiprant than those without FH. The effect was greater in those with higher baseline LDL-C and in some it was similar in magnitude to the effects of PCSK9 monoclonal antibodies. Niacin may have a role in some FH patients not reaching LDL-C targets with statins.
EAS-0105. IDENTIFICATION AND IN SILICO CHARACTERIZATION OF A NEW MUTATION IN THE LDL-RECEPTOR GENE IN AN OMANI ARAB FAMILY WITH FAMILIAL HYPERCHOLESTEROLEMIA Y. Banerjee*. Biochemistry, Sultan Qaboos University, Muscat, Oman
* Corresponding author. Autosomal dominant familial hypercholesterolemia (FH) is caused due to mutations in the low-density lipoprotein receptor (LDLR), proprotein convertase subtilisin/kexin type 9 (PCSK9) and apolipoprotein B (ApoB) genes. Little is known regarding its occurrence in the Arab population, which not only exhibits relative genetic homogeneity, but also has a lengthy tradition of consanguinity. In this study we report a new mutation causing homozygous form of the disease in an Omani-Arab family. The index patient (9-year-old female) exhibited: eye xanthelasmata and thickening of both Achilles tendons. Her off treatment lipid-profile showed: total cholesterol: 896 mg/dL, LDL-cholesterol of 853 mg/dL, APOB of 4.5 g/L, triglyceride of 71 mg/dL, and HDL-cholesterol of 0.74 mmol/L. She was treated with a combination of rosuvastatin/ezetimibe and LDL apheresis. Genetic analysis of the LDLR gene showed a homozygous frame-shift deletion mutation (272delG) at exon 3, which truncates the protein after 90 amino acid residues (versus ~840 amino acids in the wild-type). The
EAS-0874. GENETIC ASSOCIATION OF SINGLE NUCLEOTIDE POLYMORPHISMS OF ABCA1, APOA1 AND LCAT GENES IN SUBJECTS WITH LOW CONCENTRATION OF HIGH DENSITY LIPOPROTEIN-CHOLESTEROL
e109
Conclusions: In a population of dyslipidemic patients, only lipid levels but not statin treatment correlates to Lp-PLA2 levels.
Familial hypercholesterolaemia F.H. Sakri 1, N.A. Mohd Mokhsin 1, W.N.H. Wan Ahmad 1, T. Abdul Rahman 1, B.P. Hoh 2, H. Mohd Nawawi 1, *. 1 Centre for Pathology Diagnostic and Research Laboratories, Faculty of Medicine Universiti Teknologi Mara, Sungai Buloh, Malaysia; 2 Institute of Medical Molecular Biotechnology, Faculty of Medicine Universiti Teknologi Mara, Sungai Buloh, Malaysia
* Corresponding author. Aim: Coronary artery disease (CAD) is the major cause of death in the developing world, including Malaysia. It has been well established that high density lipoprotein cholesterol (HDL-c) concentration is inversely correlated with risk of CAD. Molecular defects that lead to HDL-c deficiency have been identified in several candidate genes including ATPebinding cassette transporter A1 (ABCA1), Apolipoprotein A1 (APOA1) and Lecithin cholesterol acyltransferase (LCAT). Using a “power extreme” approach, this study attempts to investigate the genetic association of three candidate genes namely ABCA1, APOA1 and LCAT among 70 Malaysian subjects with low concentration of HDL-c. Methods: Candidate genes ABCA1, APOA1 and LCAT were amplified by polymerase chain reaction (PCR) and sequenced in 210 subjects of whom 70 had low HDL-c concentration (HDL-c 0.6 mmol/L and HDL-c 0.7 mmol/L). Results: ABCA1 (rs4149337 and rs2066881) and APOA1 (rs12718465, rs2070665, rs5072 and rs7116797) variants were significantly associated with low concentration of HDL-c (p <0.05). LCAT however was not associated with the HDL-c concentration in the studied subjects. Conclusion: Our study confirms that genetic variations of ABCA1 and APOA1 play an important role in HDL-c deficiency amongst Malaysians.
Lp-PLA2 EAS-0148. LP-PLA2 LEVELS ARE INDEPENDANT OF STATIN TREATMENT IN DYSLIPIDEMIC PATIENTS D. Rosenbaum 1, *, A. mattina 1, R. bittar 2, E. bruckert 3, D. bonnefont e-Salp^ etri ere, rousselot 2, P. giral 3. 1 Cardiovascular Prevention, GH Piti e-Salp^ etri ere, Paris, France; Paris, France; 2 Lipid Biochemistry, GH Piti 3 Cardiovascular Prevention Unit, GH Piti e-Salp^ etri ere, Paris, France
* Corresponding author. Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory biomarker transported by the LDL particles that has been lnked to cardiovascular events independently of LDL-C levels and traditional cardiovascular risk factors. Statins diminishes cardiovascular risk, LDL-C and therefore LpPLA2. The aim of this study was to study the determinants of Lp-PLA2 in a population of treated and untreated dyslipidemic patients in primary prevention. Methods: All patients recruited at our outpatient clinic underwent routine clinical and biological assessments. Lp-PLA2 activity was measured using an automated colorimetric method using a rate reaction assay with 1myristoyl-2-(4-nitrophenylsuccinyl) phosphatidylcholine as a substrate (Diadexus Inc; Eurobio, France). Results: 259 patients were included with 50% under statin. Mean age was 57±13 years. Lp-PLA2 levels ranged from 60 to 381 nmol/mL/min with a mean of 168±47 ng/mL. 137 patients presented with hypertension and 55 had treatment for diabetes.. In univariate analysis, we found a strong positive correlation between Lp-PLA2, LDL-C (r¼0.57 p<0.0001) and negative with HDL-C (r¼0.26 p<0.0001) but no association with other risk factors. Moreover, Lp-PLA2 was higher in smokers. In statin-treated patients, LDL-C but not HDL-C correlated to Lp-PLA2. Multivariate analysis showed that age, LDL-C, HDL-C, and gender independently determined Lp-PLA2 but not smoking, diabetes, body mass index, blood pressures or statin treatment.
EAS-0162. IS THERE A ROLE FOR NIACIN IN FAMILIAL HYPERCHOLESTEROLAEMIA? M. Hu 1, Y.L. Yang 1, D. Masuda 2, S. Yamashita 2, B. Tomlinson 1, *. 1 Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong, China; 2 Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
* Corresponding author. Aim: Recent studies with extended release (ER) niacin in patients receiving intensive statin treatment with very low levels of low-density lipoprotein cholesterol (LDL-C) showed no benefit. In HPS2-THRIVE there was a trend for better outcomes in subgroups with higher baseline LDL-C or apolipoprotein (apo) B. We compared the lipid responses to ER niacin/ laropiprant in Chinese patients with and without familial hypercholesterolaemia (FH) to identify if those with higher baseline LDL-C might benefit. Methods: Lipid responses were compared in patients with FH (n¼30, 28 on statins) or those with other dyslipidaemias (n¼91, 38 on statins) treated with ER niacin/laropiprant combination 1000/20 mg for 4 weeks and then 2000/40 mg for 8 weeks. Results: FH patients had higher (P<0.05) baseline levels of LDL-C (3.56±0.86 mmol/L vs. 3.07±0.92 mmol/L) and had greater reductions (P<0.05) in LDL-C (-30.9±17.0% vs. -16.1±27.7%), non-high-density lipoprotein cholesterol (-32.0±17.4% vs. -22.3±18.8%) and apo B (-27.8±14.2% vs. -20.7±15.1%) than those without FH. Seven patients with FH (23%) had reductions in LDL-C of 50-60% after treatment with niacin. Multivariate regression analysis showed that patients with higher baseline LDL-C and those receiving statins had greater LDL-C reductions. Conclusion: Patients with FH had greater reductions in LDL-C with ER niacin/laropiprant than those without FH. The effect was greater in those with higher baseline LDL-C and in some it was similar in magnitude to the effects of PCSK9 monoclonal antibodies. Niacin may have a role in some FH patients not reaching LDL-C targets with statins.
EAS-0105. IDENTIFICATION AND IN SILICO CHARACTERIZATION OF A NEW MUTATION IN THE LDL-RECEPTOR GENE IN AN OMANI ARAB FAMILY WITH FAMILIAL HYPERCHOLESTEROLEMIA Y. Banerjee*. Biochemistry, Sultan Qaboos University, Muscat, Oman
* Corresponding author. Autosomal dominant familial hypercholesterolemia (FH) is caused due to mutations in the low-density lipoprotein receptor (LDLR), proprotein convertase subtilisin/kexin type 9 (PCSK9) and apolipoprotein B (ApoB) genes. Little is known regarding its occurrence in the Arab population, which not only exhibits relative genetic homogeneity, but also has a lengthy tradition of consanguinity. In this study we report a new mutation causing homozygous form of the disease in an Omani-Arab family. The index patient (9-year-old female) exhibited: eye xanthelasmata and thickening of both Achilles tendons. Her off treatment lipid-profile showed: total cholesterol: 896 mg/dL, LDL-cholesterol of 853 mg/dL, APOB of 4.5 g/L, triglyceride of 71 mg/dL, and HDL-cholesterol of 0.74 mmol/L. She was treated with a combination of rosuvastatin/ezetimibe and LDL apheresis. Genetic analysis of the LDLR gene showed a homozygous frame-shift deletion mutation (272delG) at exon 3, which truncates the protein after 90 amino acid residues (versus ~840 amino acids in the wild-type). The