The role of Lipoprotein(a) in cardiovascular disease: Current concepts and future perspectives

Berg, 1963, New serum type system in man--the lp system, Acta Pathol Microbiol Scand, 59, 369, 10.1111/j.1699-0463.1963.tb01808.x Gaubatz, 1983, Human plasma lipoprotein [a]. Structural properties, J Biol Chem, 258, 4582, 10.1016/S0021-9258(18)32663-2 Utermann, 1983, Protein composition of Lp(a) lipoprotein from human plasma, FEBS (Fed Eur Biochem Soc) Lett, 154, 357, 10.1016/0014-5793(83)80182-3 McLean, 1987, cDNA sequence of human apolipoprotein(a) is homologous to plasminogen, Nature, 330, 132, 10.1038/330132a0 Utermann, 1989, The mysteries of lipoprotein(a), Science, 246, 904, 10.1126/science.2530631 Callow, 1995, Site-specific mutagenesis demonstrates that cysteine 4326 of apolipoprotein B is required for covalent linkage with apolipoprotein (a) in vivo, J Biol Chem, 270, 23914, 10.1074/jbc.270.41.23914 Dieplinger, 1999, The seventh myth of lipoprotein(a): where and how is it assembled?, Curr Opin Lipidol, 10, 275, 10.1097/00041433-199906000-00010 Koschinsky, 1993, Identification of the cysteine residue in apolipoprotein(a) that mediates extracellular coupling with apolipoprotein B-100, J Biol Chem, 268, 19819, 10.1016/S0021-9258(19)36587-1 Kronenberg, 2013, Lipoprotein(a): resurrected by genetics, J Intern Med, 273, 6, 10.1111/j.1365-2796.2012.02592.x Haibach, 1998, The number of kringle IV repeats 3-10 is invariable in the human apo(a) gene, Gene, 208, 253, 10.1016/S0378-1119(97)00657-4 Tsimikas, 2017, A Test in Context: Lipoprotein(a): Diagnosis, Prognosis, Controversies, and Emerging Therapies, J Am Coll Cardiol, 69, 692, 10.1016/j.jacc.2016.11.042 Leibundgut, 2013, Determinants of binding of oxidized phospholipids on apolipoprotein (a) and lipoprotein (a)1, J Lipid Res, 54, 2815, 10.1194/jlr.M040733 Kraft, 1989, Changes of genetic apolipoprotein phenotypes caused by liver transplantation. Implications for apolipoprotein synthesis, J Clin Invest, 83, 137, 10.1172/JCI113849 Lobentanz, 1998, Intracellular metabolism of human apolipoprotein(a) in stably transfected Hep G2 cells, Biochemistry, 37, 5417, 10.1021/bi972761t White, 1994, Cell surface assembly of lipoprotein(a) in primary cultures of baboon hepatocytes, J Biol Chem, 269, 28716, 10.1016/S0021-9258(19)61964-2 White, 1994, Intracellular processing of apo(a) in primary baboon hepatocytes, Chem Phys Lipids, 67–68, 123, 10.1016/0009-3084(94)90131-7 White, 1997, Biogenesis of Lp(a) in transgenic mouse hepatocytes, Clin Genet, 52, 326, 10.1111/j.1399-0004.1997.tb04350.x Edelstein, 1994, Oleate stimulates the formation of triglyceride-rich particles containing apoB100-apo(a) in long-term primary cultures of human hepatocytes, Chem Phys Lipids, 67–68, 135, 10.1016/0009-3084(94)90132-5 Bonen, 1997, Expression of a recombinant apolipoprotein(a) in HepG2 cells. Evidence for intracellular assembly of lipoprotein(a), J Biol Chem, 272, 5659, 10.1074/jbc.272.9.5659 Su, 1998, Metabolism of Apo(a) and ApoB100 of lipoprotein(a) in women: effect of postmenopausal estrogen replacement, J Clin Endocrinol Metab, 83, 3267 Clarke, 2009, Genetic variants associated with Lp(a) lipoprotein level and coronary disease, N Engl J Med, 361, 2518, 10.1056/NEJMoa0902604 Boerwinkle, 1992, Apolipoprotein(a) gene accounts for greater than 90% of the variation in plasma lipoprotein(a) concentrations, J Clin Invest, 90, 52, 10.1172/JCI115855 Schmidt, 2016, Structure, function, and genetics of lipoprotein (a), J Lipid Res, 57, 1339, 10.1194/jlr.R067314 Hrzenjak, 2003, Galactose-specific asialoglycoprotein receptor is involved in lipoprotein (a) catabolism, Biochem J, 376, 765, 10.1042/bj20030932 Cain, 2005, Lipoprotein [a] is cleared from the plasma primarily by the liver in a process mediated by apolipoprotein [a], J Lipid Res, 46, 2681, 10.1194/jlr.M500249-JLR200 McCormick, 2019, Lipoprotein(a) catabolism: a case of multiple receptors, Pathology, 51, 155, 10.1016/j.pathol.2018.11.003 Tabas, 2007, Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic implications, Circulation, 116, 1832, 10.1161/CIRCULATIONAHA.106.676890 Borén, 2016, The central role of arterial retention of cholesterol-rich apolipoprotein-B-containing lipoproteins in the pathogenesis of atherosclerosis: a triumph of simplicity, Curr Opin Lipidol, 27, 473, 10.1097/MOL.0000000000000330 Berliner, 2009, The role of oxidized phospholipids in atherosclerosis, J Lipid Res, 50, S207, 10.1194/jlr.R800074-JLR200 Bergmark, 2008, A novel function of lipoprotein [a] as a preferential carrier of oxidized phospholipids in human plasma, J Lipid Res, 49, 2230, 10.1194/jlr.M800174-JLR200 Tsimikas, 2003, Temporal increases in plasma markers of oxidized low-density lipoprotein strongly reflect the presence of acute coronary syndromes, J Am Coll Cardiol, 41, 360, 10.1016/S0735-1097(02)02769-9 Tsimikas, 2005, Oxidized Phospholipids, Lp(a) Lipoprotein, and Coronary Artery Disease, N Engl J Med, 12 Tsimikas, 2009, Relationship of Oxidized Phospholipids on Apolipoprotein B-100 Particles to Race/Ethnicity, Apolipoprotein(a) Isoform Size, and Cardiovascular Risk Factors: Results From the Dallas Heart Study, Circulation, 119, 1711, 10.1161/CIRCULATIONAHA.108.836940 Varvel, 2016, Prevalence of Elevated Lp(a) Mass Levels and Patient Thresholds in 532 359 Patients in the United States, Arterioscler Thromb Vasc Biol, 36, 2239, 10.1161/ATVBAHA.116.308011 van der Valk, 2016, Oxidized Phospholipids on Lipoprotein(a) Elicit Arterial Wall Inflammation and an Inflammatory Monocyte Response in Humans, Circulation, 134, 611, 10.1161/CIRCULATIONAHA.116.020838 Greenberg, 2006, Oxidized phosphatidylserine–CD36 interactions play an essential role in macrophage-dependent phagocytosis of apoptotic cells, J Exp Med, 203, 2613, 10.1084/jem.20060370 Caplice, 2001, Lipoprotein (a) binds and inactivates tissue factor pathway inhibitor: a novel link between lipoproteins and thrombosis, Blood, 98, 2980, 10.1182/blood.V98.10.2980 Kamstrup, 2012, Genetic Evidence That Lipoprotein(a) Associates With Atherosclerotic Stenosis Rather Than Venous Thrombosis, Arterioscler Thromb Vasc Biol, 32, 1732, 10.1161/ATVBAHA.112.248765 Lippi, 1999, Lipoprotein(a) concentration is not associated with venous thromboembolism in a case control study, Haematologica, 84, 726 Erqou, 2009, Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality, J Am Med Assoc, 302, 412, 10.1001/jama.2009.1063 Kamstrup, 2009, Genetically Elevated Lipoprotein(a) and Increased Risk of Myocardial Infarction, J Am Med Assoc, 301, 2331, 10.1001/jama.2009.801 Rallidis, 2020, Familial hypercholesterolaemia: New directions on the diagnosis and treatment of an old disease, Hellenic J Cardiol, 10.1016/j.hjc.2020.06.014 Langsted, 2016, High lipoprotein(a) as a possible cause of clinical familial hypercholesterolaemia: a prospective cohort study, The Lancet Diabetes & Endocrinology, 4, 577, 10.1016/S2213-8587(16)30042-0 von Eckardstein, 2001, Lipoprotein(a) further increases the risk of coronary events in men with high global cardiovascular risk, J Am Coll Cardiol, 37, 434, 10.1016/S0735-1097(00)01126-8 Anon, 2013, Large-scale association analysis identifies new risk loci for coronary artery disease, Nat Genet, 45, 25, 10.1038/ng.2480 Burgess, 2018, Association of LPA Variants With Risk of Coronary Disease and the Implications for Lipoprotein(a)-Lowering Therapies: A Mendelian Randomization Analysis, JAMA Cardiol, 3, 619, 10.1001/jamacardio.2018.1470 Kamstrup, 2013, Extreme Lipoprotein(a) Levels and Improved Cardiovascular Risk Prediction, J Am Coll Cardiol, 61, 1146, 10.1016/j.jacc.2012.12.023 Kamstrup, 2017, Oxidized Phospholipids and Risk of Calcific Aortic Valve Disease - The Copenhagen General Population Study, Arterioscler Thromb Vasc Biol, 37, 1570, 10.1161/ATVBAHA.116.308761 Vongpromek, 2015, Lipoprotein(a) levels are associated with aortic valve calcification in asymptomatic patients with familial hypercholesterolaemia, J Intern Med, 278, 166, 10.1111/joim.12335 Arsenault Benoit, 2014, Dubé Marie-Pierre, et al. Lipoprotein(a) Levels, Genotype, and Incident Aortic Valve Stenosis, Circulation: Cardiovascular Genetics, 7, 304 Thanassoulis, 2013, Genetic Associations with Valvular Calcification and Aortic Stenosis, N Engl J Med, 368, 503, 10.1056/NEJMoa1109034 Capoulade, 2015, Oxidized Phospholipids, Lipoprotein(a), and Progression of Calcific Aortic Valve Stenosis, J Am Coll Cardiol, 66, 1236, 10.1016/j.jacc.2015.07.020 Zheng, 2019, Lipoprotein(a) and Oxidized Phospholipids Promote Valve Calcification in Patients With Aortic Stenosis, J Am Coll Cardiol, 73, 2150, 10.1016/j.jacc.2019.01.070 Tsimikas, 2004, Percutaneous Coronary Intervention Results in Acute Increases in Oxidized Phospholipids and Lipoprotein(a): Short-Term and Long-Term Immunologic Responses to Oxidized Low-Density Lipoprotein, Circulation, 109, 3164, 10.1161/01.CIR.0000130844.01174.55 Rallidis, 2018, High levels of lipoprotein (a) and premature acute coronary syndrome, Atherosclerosis, 269, 29, 10.1016/j.atherosclerosis.2017.12.011 Isser, 2001, Lipoprotein (a) and lipid levels in young patients with myocardial infarction and their first-degree relatives, Indian Heart J, 53, 463 Faghihnia, 2010, Changes in lipoprotein(a), oxidized phospholipids, and LDL subclasses with a low-fat high-carbohydrate diet, J Lipid Res, 51, 3324, 10.1194/jlr.M005769 Berk, 2017, Effect of diet-induced weight loss on lipoprotein(a) levels in obese individuals with and without type 2 diabetes, Diabetologia, 60, 989, 10.1007/s00125-017-4246-y Tsimikas, 2019, Statin therapy increases lipoprotein(a) levels, Eur Heart J Willeit, 2018, Baseline and on-statin treatment lipoprotein(a) levels for prediction of cardiovascular events: individual patient-data meta-analysis of statin outcome trials, Lancet, 392, 1311, 10.1016/S0140-6736(18)31652-0 Lincoff, 2017, Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease, N Engl J Med, 376, 1933, 10.1056/NEJMoa1609581 Sahebkar, 2016, Effect of extended-release niacin on plasma lipoprotein(a) levels: A systematic review and meta-analysis of randomized placebo-controlled trials, Metab, Clin Exp, 65, 1664, 10.1016/j.metabol.2016.08.007 Yeang, 2016, Effect of therapeutic interventions on oxidized phospholipids on apolipoprotein B100 and lipoprotein(a), Journal of Clinical Lipidology, 10, 594, 10.1016/j.jacl.2016.01.005 Albers, 2013, Relationship of Apolipoproteins A-1 and B, and Lipoprotein(a) to Cardiovascular Outcomes: The AIM-HIGH Trial (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglyceride and Impact on Global Health Outcomes), J Am Coll Cardiol, 62, 1575, 10.1016/j.jacc.2013.06.051 Lamina, 2019, Estimation of the Required Lipoprotein(a)-Lowering Therapeutic Effect Size for Reduction in Coronary Heart Disease Outcomes: A Mendelian Randomization Analysis, JAMA Cardiol, 4, 575, 10.1001/jamacardio.2019.1041 Gaudet, 2014, Effect of Alirocumab, a Monoclonal Proprotein Convertase Subtilisin/Kexin 9 Antibody, on Lipoprotein(a) Concentrations (a Pooled Analysis of 150 mg Every Two Weeks Dosing from Phase 2 Trials), Am J Cardiol, 114, 711, 10.1016/j.amjcard.2014.05.060 Raal, 2014, Reduction in lipoprotein(a) with PCSK9 monoclonal antibody evolocumab (AMG 145): a pooled analysis of more than 1,300 patients in 4 phase II trials, J Am Coll Cardiol, 63, 1278, 10.1016/j.jacc.2014.01.006 Sabatine, 2017, Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease, N Engl J Med, 376, 1713, 10.1056/NEJMoa1615664 Schwartz, 2018, Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome, N Engl J Med, 379, 2097, 10.1056/NEJMoa1801174 O'Donoghue Michelle, 2019, Lipoprotein(a), PCSK9 Inhibition, and Cardiovascular Risk, Circulation, 139, 1483, 10.1161/CIRCULATIONAHA.118.037184 Bittner, 2020, Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome, J Am Coll Cardiol, 75, 133, 10.1016/j.jacc.2019.10.057 Rallidis, 2016, PCSK9 inhibition as an emerging lipid lowering therapy: Unanswered questions, Hellenic J Cardiol, 57, 86, 10.1016/j.hjc.2016.03.002 Yang, 2016, Analysis of the association between plasma PCSK9 and Lp(a) in Han Chinese, J Endocrinol Invest, 39, 875, 10.1007/s40618-016-0433-9 Sarah, 2018, Impact of Apolipoprotein(a) Isoform Size on Lipoprotein(a) Lowering in the HPS2-THRIVE Study, Circulation: Genomic and Precision Medicine, 11 Graham, 2016, Antisense inhibition of apolipoprotein (a) to lower plasma lipoprotein (a) levels in humans, J Lipid Res, 57, 340, 10.1194/jlr.R052258 Tsimikas, 2015, Antisense therapy targeting apolipoprotein(a): a randomised, double-blind, placebo-controlled phase 1 study, Lancet, 386, 1472, 10.1016/S0140-6736(15)61252-1 Viney, 2016, Antisense oligonucleotides targeting apolipoprotein(a) in people with raised lipoprotein(a): two randomised, double-blind, placebo-controlled, dose-ranging trials, Lancet, 388, 2239, 10.1016/S0140-6736(16)31009-1 Tsimikas, 2020, Lipoprotein(a) Reduction in Persons with Cardiovascular Disease, N Engl J Med, 382, 244, 10.1056/NEJMoa1905239 Kronenberg, 2019, The challenges of measuring Lp(a): A fight against Hydra?, Atherosclerosis, 289, 181, 10.1016/j.atherosclerosis.2019.08.019 Marcovina, 1995, Effect of the number of apolipoprotein(a) kringle 4 domains on immunochemical measurements of lipoprotein(a), Clin Chem, 41, 246, 10.1093/clinchem/41.2.246 Marcovina, 2016, Lipoprotein (a) measurements for clinical application, J Lipid Res, 57, 526, 10.1194/jlr.R061648 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 Nordestgaard, 2010, Lipoprotein(a) as a cardiovascular risk factor: current status, Eur Heart J, 31, 2844, 10.1093/eurheartj/ehq386 Mach, 2019, ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk, Eur Heart J, 41, 111, 10.1093/eurheartj/ehz455 Tsimikas, 2012, Lipoprotein(a) as a potential causal genetic risk factor of cardiovascular disease: a rationale for increased efforts to understand its pathophysiology and develop targeted therapies, J Am Coll Cardiol, 60, 716, 10.1016/j.jacc.2012.04.038