Association of PCSK9 Variants With the Risk of Atherosclerotic Cardiovascular Disease and Variable Responses to PCSK9 Inhibitor Therapy

Current Problems in Cardiology - Tập 47 - Trang 101043 - 2022
Chayakrit Krittanawong1,2, Muzamil Khawaja1,2, Robert S Rosenson3, Christopher I. Amos4, Vijay Nambi1,2, Carl J Lavie5, Salim S. Virani1,2
1The Michael E. DeBakey VA Medical Center, Houston, TX
2Section of Cardiology, Baylor College of Medicine, Houston, TX
3Director, Cardiometabolics Unit, Mount Sinai Hospital, Mount Sinai Heart, NY, NY
4Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, TX
5John Ochsner Heart and Vascular Institute, Ochsner Clinical School, The University of Queensland School of Medicine, New Orleans, LA

Tài liệu tham khảo

Davies, 2018, Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians, BMJ, 362, k601, 10.1136/bmj.k601 Bays, 2018, Assessment of the 1% of patients with consistent <15% reduction in low-density lipoprotein cholesterol: pooled analysis of 10 phase 3 ODYSSEY alirocumab trials, Cardiovasc Drug Ther, 32, 175, 10.1007/s10557-018-6784-z Johnson, 2001, Drug target pharmacogenomics: an overview, Am J Pharmacogenomics, 1, 271, 10.2165/00129785-200101040-00004 Virani, 2021, American heart association council on E, prevention statistics C and stroke statistics S. heart disease and stroke statistics-2021 update: a report from the American heart association, Circulation, 143, e254, 10.1161/CIR.0000000000000950 Fryar, 2012, Prevalence of uncontrolled risk factors for cardiovascular disease: United States, 1999-2010, NCHS Data Brief, 1 Catapano, 2016, 2016 ESC/EAS guidelines for the management of dyslipidaemias, Eur Heart J, 37, 2999, 10.1093/eurheartj/ehw272 Ference, 2012, Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease: a Mendelian randomization analysis, J Am Coll Cardiol, 60, 2631, 10.1016/j.jacc.2012.09.017 Maxwell, 2004, Adenoviral-mediated expression of Pcsk9 in mice results in a low-density lipoprotein receptor knockout phenotype, Proc Natl Acad Sci USA, 101, 7100, 10.1073/pnas.0402133101 Park, 2004, Post-transcriptional regulation of low density lipoprotein receptor protein by proprotein convertase subtilisin/kexin type 9a in mouse liver, J Biol Chem, 279, 50630, 10.1074/jbc.M410077200 Benjannet, 2004, NARC-1/PCSK9 and its natural mutants: zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol, J Biol Chem, 279, 48865, 10.1074/jbc.M409699200 Di Taranto MD, 2017, Identification and in vitro characterization of two new PCSK9 Gain of Function variants found in patients with Familial Hypercholesterolemia, Sci Rep, 7, 15282, 10.1038/s41598-017-15543-x Kaya, 2017, PCSK 9 gain-of-function mutations (R496W and D374Y) and clinical cardiovascular characteristics in a cohort of Turkish patients with familial hypercholesterolemia, Anatol J Cardiol, 18, 266 Manocha, 2016, Lipoprotein: a unique independent risk factor for coronary artery disease, Indian J Clin Biochem, 31, 13, 10.1007/s12291-015-0483-3 Iannuzzo, 2021, Lipoprotein(a) where do we stand? from the physiopathology to innovative terapy, Biomedicines, 9, 10.3390/biomedicines9070838 Bennet, 2008, Lipoprotein(a) levels and risk of future coronary heart disease: large-scale prospective data, Arch Intern Med, 168, 598, 10.1001/archinte.168.6.598 Craig, 1998, Lipoprotein(a) as a risk factor for ischemic heart disease: metaanalysis of prospective studies, Clin Chem, 44, 2301, 10.1093/clinchem/44.11.2301 Danesh, 2000, Lipoprotein(a) and coronary heart disease. Meta-analysis of prospective studies, Circulation, 102, 1082, 10.1161/01.CIR.102.10.1082 Kamstrup, 2009, Genetically elevated lipoprotein(a) and increased risk of myocardial infarction, Jama, 301, 2331, 10.1001/jama.2009.801 Kronenberg, 2013, Lipoprotein(a): resurrected by genetics, J Intern Med, 273, 6, 10.1111/j.1365-2796.2012.02592.x Sandholzer, 1992, Apo(a) isoforms predict risk for coronary heart disease. A study in six populations, Arterioscler Thromb, 12, 1214, 10.1161/01.ATV.12.10.1214 Tsimikas, 2018, NHLBI working group recommendations to reduce lipoprotein(a)-mediated risk of cardiovascular disease and aortic stenosis, J Am Coll Cardiol, 71, 177, 10.1016/j.jacc.2017.11.014 Reyes-Soffer, 2017, Effects of PCSK9 inhibition with alirocumab on lipoprotein metabolism in healthy humans, Circulation, 135, 352, 10.1161/CIRCULATIONAHA.116.025253 Villard, 2016, PCSK9 modulates the secretion but not the cellular uptake of lipoprotein(a) ex vivo: an effect blunted by Alirocumab, JACC Basic Transl Sci, 1, 419, 10.1016/j.jacbts.2016.06.006 O'Donoghue, 2019, Lipoprotein(a), PCSK9 inhibition, and cardiovascular risk, Circulation, 139, 1483, 10.1161/CIRCULATIONAHA.118.037184 Reiner, 2015, Management of patients with familial hypercholesterolaemia, Nat Rev Cardiol, 12, 565, 10.1038/nrcardio.2015.92 Reiner, 2015, PCSK9 inhibitors – past, present and future, Expert Opin Drug Metab Toxicol, 11, 1517, 10.1517/17425255.2015.1075506 Navarese, 2015, Effects of proprotein convertase Subtilisin/Kexin Type 9 antibodies in adults with hypercholesterolemia: a systematic review and meta-analysis, Ann Intern Med, 163, 40, 10.7326/M14-2957 Ito, 2015, Challenges in the diagnosis and treatment of homozygous familial hypercholesterolemia, Drugs, 75, 1715, 10.1007/s40265-015-0466-y Sabatine, 2017, Evolocumab and clinical outcomes in patients with cardiovascular disease, N Engl J Med, 376, 1713, 10.1056/NEJMoa1615664 Robinson, 2014, Effect of evolocumab or ezetimibe added to moderate- or high-intensity statin therapy on LDL-C lowering in patients with hypercholesterolemia: the LAPLACE-2 randomized clinical trial, Jama, 311, 1870, 10.1001/jama.2014.4030 Koren, 2014, Anti-PCSK9 monotherapy for hypercholesterolemia: the MENDEL-2 randomized, controlled phase III clinical trial of evolocumab, J Am Coll Cardiol, 63, 2531, 10.1016/j.jacc.2014.03.018 Koren, 2019, Long-term efficacy and safety of Evolocumab in patients with hypercholesterolemia, J Am Coll Cardiol, 74, 2132, 10.1016/j.jacc.2019.08.1024 Koskinas, 2019, Evolocumab for early reduction of LDL cholesterol levels in patients with acute coronary syndromes (EVOPACS), J Am Coll Cardiol, 74, 2452, 10.1016/j.jacc.2019.08.010 Raal, 2015, Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial, Lancet, 385, 341, 10.1016/S0140-6736(14)61374-X Raal, 2015, PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial, Lancet, 385, 331, 10.1016/S0140-6736(14)61399-4 Effect of Evolocumab in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or Stroke (VESALIUS-CV). Kereiakes, 2015, Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: the ODYSSEY COMBO I study, Am Heart J, 169, 906, 10.1016/j.ahj.2015.03.004 Roth, 2014, Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: results of a 24 week, double-blind, randomized Phase 3 trial, Int J Cardiol, 176, 55, 10.1016/j.ijcard.2014.06.049 Cannon, 2015, Efficacy and safety of alirocumab in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia on maximally tolerated doses of statins: the ODYSSEY COMBO II randomized controlled trial, Eur Heart J, 36, 1186, 10.1093/eurheartj/ehv028 Roth EM, Moriarty PM, Bergeron J, investigators OCI, et al. A phase III randomized trial evaluating alirocumab 300 mg every 4 weeks as monotherapy or add-on to statin: ODYSSEY CHOICE I. Atherosclerosis. 2016;254:254-262. Robinson, 2015, Efficacy and safety of alirocumab in reducing lipids and cardiovascular events, N Engl J Med, 372, 1489, 10.1056/NEJMoa1501031 Kastelein, 2015, ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia, Eur Heart J, 36, 2996 Blom, 2020, Efficacy and Safety of Alirocumab in Adults With Homozygous Familial Hypercholesterolemia: The ODYSSEY HoFH Trial, J Am Coll Cardiol, 76, 131, 10.1016/j.jacc.2020.05.027 Gavrilov, 2012, Therapeutic siRNA: principles, challenges, and strategies, Yale J Biol Med, 85, 187 Raal, 2020, Inclisiran for the Treatment of Heterozygous Familial Hypercholesterolemia, N Engl J Med, 382, 1520, 10.1056/NEJMoa1913805 Ray, 2020, Two phase 3 trials of Inclisiran in patients with elevated LDL cholesterol, N Engl J Med, 382, 1507, 10.1056/NEJMoa1912387 Wright, 2021, Pooled patient-level analysis of Inclisiran trials in patients with familial hypercholesterolemia or atherosclerosis, J Am Coll Cardiol, 77, 1182, 10.1016/j.jacc.2020.12.058 Bartel, 2004, MicroRNAs: genomics, biogenesis, mechanism, and function, Cell, 116, 281, 10.1016/S0092-8674(04)00045-5 Jovanovic, 2006, miRNAs and apoptosis: RNAs to die for, Oncogene, 25, 6176, 10.1038/sj.onc.1209912 Lin, 2015, MicroRNA biogenesis pathways in cancer, Nature reviews Cancer, 15, 321, 10.1038/nrc3932 Moore, 2010, microRNAs and cholesterol metabolism, Trends Endocrinol Metab, 21, 699, 10.1016/j.tem.2010.08.008 Goedeke, 2016, miRNA regulation of LDL-cholesterol metabolism, Biochim Biophys Acta Mol Cell Biol Lipids, 1861, 2047, 10.1016/j.bbalip.2016.03.007 Esau, 2006, miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting, Cell metabolism, 3, 87, 10.1016/j.cmet.2006.01.005 Mohammadmoradi, 2017, Abstract 566: MicroRNA-146a deficiency prevents PCSK9 gain-of-function mutation-induced hypercholesterolemia in mice, Arterioscler Thromb Vasc Biol, 37, A566, 10.1161/atvb.37.suppl_1.566 Bai, 2017, A retrospective study of NENs and miR-224 promotes apoptosis of BON-1 cells by targeting PCSK9 inhibition, Oncotarget, 8, 6929, 10.18632/oncotarget.14322 Alvarez, 2015, MicroRNA-27a decreases the level and efficiency of the LDL receptor and contributes to the dysregulation of cholesterol homeostasis, Atherosclerosis, 242, 595, 10.1016/j.atherosclerosis.2015.08.023 Momtazi, 2017, PCSK9 and diabetes: is there a link?, Drug Discovery Today, 22, 883, 10.1016/j.drudis.2017.01.006 Momtazi, 2017, PCSK9 inhibitors in sepsis: a new potential indication?, Expert Opin Investig Drugs, 26, 137, 10.1080/13543784.2017.1272570 Li, 2016, MicroRNA-132 cause apoptosis of glioma cells through blockade of the SREBP-1c metabolic pathway related to SIRT1, Biomed Pharmacother, 78, 177, 10.1016/j.biopha.2016.01.022 Li, 2013, MicroRNA-185 and 342 inhibit tumorigenicity and induce apoptosis through blockade of the SREBP metabolic pathway in prostate cancer cells, PloS one, 8, e70987, 10.1371/journal.pone.0070987 Yang, 2014, Identification of miR-185 as a regulator of de novo cholesterol biosynthesis and low density lipoprotein uptake, J Lipid Res, 55, 226, 10.1194/jlr.M041335 Cohen, 2005, Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9, Nat Genet, 37, 161, 10.1038/ng1509 Berge, 2006, Missense mutations in the PCSK9 gene are associated with hypocholesterolemia and possibly increased response to statin therapy, Arterioscler Thromb Vasc Biol, 26, 1094, 10.1161/01.ATV.0000204337.81286.1c Kotowski, 2006, A spectrum of PCSK9 alleles contributes to plasma levels of low-density lipoprotein cholesterol, Am J Hum Genet, 78, 410, 10.1086/500615 Cohen, 2006, Sequence variations in PCSK9, low LDL, and protection against coronary heart disease, N Engl J Med, 354, 1264, 10.1056/NEJMoa054013 Kent, 2017, PCSK9 loss-of-function variants, low-density lipoprotein cholesterol, and risk of coronary heart disease and stroke: data from 9 studies of blacks and whites, Circ Cardiovasc Genet, 10, 10.1161/CIRCGENETICS.116.001632 Benn, 2010, PCSK9 R46L, low-density lipoprotein cholesterol levels, and risk of ischemic heart disease: 3 independent studies and meta-analyses, J Am Coll Cardiol, 55, 2833, 10.1016/j.jacc.2010.02.044 Scartezini, 2007, The PCSK9 gene R46L variant is associated with lower plasma lipid levels and cardiovascular risk in healthy U.K. men, Clinical Sci, 113, 435, 10.1042/CS20070150 Chernogubova, 2012, Common and low-frequency genetic variants in the PCSK9 locus influence circulating PCSK9 levels, Arterioscler Thromb Vasc Biol, 32, 1526, 10.1161/ATVBAHA.111.240549 Postmus, 2013, PCSK9 SNP rs11591147 is associated with low cholesterol levels but not with cognitive performance or noncardiovascular clinical events in an elderly population, J Lipid Res, 54, 561, 10.1194/jlr.M033969 Tsai, 2015, Both rare and common variants in PCSK9 influence plasma low-density lipoprotein cholesterol level in American Indians, J Clin Endocrinol Metab, 100, E345, 10.1210/jc.2014-3340 Kathiresan, 2008, A PCSK9 missense variant associated with a reduced risk of early-onset myocardial infarction, N Engl J Med, 358, 2299, 10.1056/NEJMc0707445 Guella, 2010, Effects of PCSK9 genetic variants on plasma LDL cholesterol levels and risk of premature myocardial infarction in the Italian population, J Lipid Res, 51, 3342, 10.1194/jlr.M010009 Nikpay, 2015, A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease, Nat Genet, 47, 1121, 10.1038/ng.3396 Jeenduang, 2015, Combined PCSK9 and APOE polymorphisms are genetic risk factors associated with elevated plasma lipid levels in a Thai population, Lipids, 50, 543, 10.1007/s11745-015-4017-9 Mayne, 2013, Differential effects of PCSK9 loss of function variants on serum lipid and PCSK9 levels in Caucasian and African Canadian populations, Lipids Health Dis, 12, 70, 10.1186/1476-511X-12-70 Shioji, 2004, Genetic variants in PCSK9 affect the cholesterol level in Japanese, J Hum Genet, 49, 109, 10.1007/s10038-003-0114-3 He, 2016, E670G polymorphism of PCSK9 gene of patients with coronary heart disease among Han population in Hainan and three provinces in the northeast of China, Asian Pac J Trop Med, 9, 172, 10.1016/j.apjtm.2016.01.008 Hsu, 2009, The PCSK9 gene E670G polymorphism affects low-density lipoprotein cholesterol levels but is not a risk factor for coronary artery disease in ethnic Chinese in Taiwan, Clin Chem Lab Med, 47, 154, 10.1515/CCLM.2009.032 Slimani, 2014, Effect of E670G Polymorphism in PCSK9 gene on the risk and severity of coronary heart disease and ischemic stroke in a Tunisian cohort, J Mol Neurosci, 53, 150, 10.1007/s12031-014-0238-2 Xu, 2010, Minor allele C of chromosome 1p32 single nucleotide polymorphism rs11206510 confers risk of ischemic stroke in the Chinese Han population, Stroke, 41, 1587, 10.1161/STROKEAHA.110.583096 Kathiresan, 2009, Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants, Nat Genet, 41, 334, 10.1038/ng.327 Zhang, 2013, Association between PCSK9 and LDLR gene polymorphisms with coronary heart disease: case-control study and meta-analysis, Clinical biochemistry, 46, 727, 10.1016/j.clinbiochem.2013.01.013 Dorado, 2014, Relationship between the CYP2C9 IVS8-109A>T polymorphism and high losartan hydroxylation in healthy Ecuadorian volunteers, Pharmacogenomics, 15, 1417, 10.2217/pgs.14.85 Hamadeh, 2014, Impact of CYP2D6 polymorphisms on clinical efficacy and tolerability of metoprolol tartrate, Clin Pharmacol Ther, 96, 175, 10.1038/clpt.2014.62 Uchida, 2003, Altered pharmacokinetics and excessive hypotensive effect of candesartan in a patient with the CYP2C91/3 genotype, Clin Pharmacol Ther, 74, 505, 10.1016/j.clpt.2003.08.001 Higashi, 2002, Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy, Jama, 287, 1690, 10.1001/jama.287.13.1690 Cohen, 2006, Sequence variations in PCSK9, low LDL, and protection against coronary heart disease, N Engl J Med, 354, 1264, 10.1056/NEJMoa054013 Huang, 2009, Longitudinal association of PCSK9 sequence variations with low-density lipoprotein cholesterol levels: the coronary artery risk development in young adults study, Circ Cardiovasc Genet, 2, 354, 10.1161/CIRCGENETICS.108.828467 Qamar, 2019, Interindividual variation in low-density lipoprotein cholesterol level reduction with Evolocumab: an analysis of FOURIER trial data, JAMA Cardiol, 4, 59, 10.1001/jamacardio.2018.4178 Ridker, 2017, Lipid-reduction variability and antidrug-antibody formation with Bococizumab, N Engl J Med, 376, 1517, 10.1056/NEJMoa1614062 Farnier, 2015, An evaluation of alirocumab for the treatment of hypercholesterolemia, Expert Rev Cardiovasc Ther, 13, 1307, 10.1586/14779072.2015.1111759 Warden, 2020, Unusual responses to PCSK9 inhibitors in a clinical cohort utilizing a structured follow-up protocol, Am J Prev Cardiol, 1, 10.1016/j.ajpc.2020.100012 Edmiston, 2017, Discordant response of low-density lipoprotein cholesterol and lipoprotein(a) levels to monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9, J Clin Lipidol, 11, 667, 10.1016/j.jacl.2017.03.001 Cong, 2013, Multiplex genome engineering using CRISPR/Cas systems, Science, 339, 819, 10.1126/science.1231143 Carreras, 2019, In vivo genome and base editing of a human PCSK9 knock-in hypercholesterolemic mouse model, BMC Biol, 17, 4, 10.1186/s12915-018-0624-2 Komor, 2016, Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage, Nature, 533, 420, 10.1038/nature17946 Musunuru, 2021, In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates, Nature, 593, 429, 10.1038/s41586-021-03534-y Ding, 2014, Permanent alteration of PCSK9 with in vivo CRISPR-Cas9 genome editing, Circ Res, 115, 488, 10.1161/CIRCRESAHA.115.304351 Wang, 2021, Long-term stable reduction of low-density lipoprotein in nonhuman primates following in vivo genome editing of PCSK9, Mol Ther, 29, 2019, 10.1016/j.ymthe.2021.02.020 Krittanawong, 2016, Practical pharmacogenomic approaches to heart failure therapeutics, Curr Treat Options Cardiovasc Med, 18, 60, 10.1007/s11936-016-0483-5 Blackston, 2020, Cardiovascular disease events and mortality after myocardial infarction among black and white adults: REGARDS study, Circ Cardiovasc Qual Outcomes, 13, 10.1161/CIRCOUTCOMES.120.006683