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LIPID DISORDERS / STATE OF THE ART PAPER
2024: The Year in Cardiovascular Disease - The Year of Lipoprotein(a) – Research Advances and New Findings.
1
Department of Preventive Cardiology and Lipidology, Medical University of Lodz (MUL), Lodz, Poland
2
CGH Medical Center, Sterling, IL, and Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA
3
Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA, USA
4
Lipoprotein Metabolism Laboratory, Translational Vascular Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
5
Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA
6
Faculty of Medicine, the John Paul II Catholic University of Lublin (KUL), Lublin, Poland
7
Department of Cardiology and Adult Congenital Heart Diseases, Polish Mother’s Memorial Hospital Research Institute (PMMHRI), Lodz, Poland
Submission date: 2024-12-07
Final revision date: 2025-02-09
Acceptance date: 2025-02-20
Online publication date: 2025-02-22
Corresponding author
Bożena Sosnowska
Department of Preventive , Cardiology and Lipidology Medical University of Lodz, Rzgowska 281/289, 93-338 Lodz, Poland
Department of Preventive , Cardiology and Lipidology Medical University of Lodz, Rzgowska 281/289, 93-338 Lodz, Poland
Arch Med Sci 2025;21(2):355-373
KEYWORDS
aortic valve calcificationatherosclerosiscardiovascular diseaselipoprotein(a)apo(a) isoformsRNA therapeuticsoutcomesvariability
TOPICS
ABSTRACT
Elevated plasma lipoprotein(a) [Lp(a)] levels, which occur in as many as 1.5 billion people worldwide, are an independent and causal risk factor for atherosclerotic cardiovascular disease and calcific aortic valve disease. Unlike low-density lipoprotein cholesterol, Lp(a) levels are approximately 70–90% genetically determined. Currently, no approved pharmacological therapies specifically target lowering Lp(a) concentrations. Several drugs, mainly RNA-based therapies, that specifically and potently lower Lp(a), are under investigation. Three of these new therapeutic agents are advancing through clinical development to evaluate whether reducing Lp(a) levels can decrease cardiovascular risk. The outcomes of these trials could potentially transform cardiovascular disease prevention strategies; however, once approved, the drugs will likely be used for secondary prevention, and ongoing strategies for managing elevated Lp(a) in primary prevention will be important. Lipoprotein(a) research is a rapidly evolving field, but unanswered questions remain concerning the physiological function of Lp(a) and its true pathogenic mechanisms. This review of Lp(a) research focuses on new findings and clinical trial results that appeared in 2024.
REFERENCES (179)
1.
Cybulska B, Kłosiewicz-Latoszek L, Penson PE, Banach M. What do we know about the role of lipoprotein(a) in atherogenesis 57 years after its discovery? Prog Cardiovasc Dis 2020; 63: 219-27.
2.
Tsimikas S, Marcovina SM. Ancestry, lipoprotein(a), and cardiovascular risk thresholds. J Am Coll Cardiol 2022; 80: 934-46.
3.
Sosnowska B, Lewek J, Adach W, et al. The prevalence, patients’ characteristics, and hyper-Lp(a)-emia risk factors in the Polish population. The first results from the PMMHRI-Lp(a) Registry. Prog Cardiovasc Dis 2024; 86: 54-61.
4.
Dyrbuś K, Mędrala Z, Konsek K, et al. Lipoprotein(a) and its impact on cardiovascular disease – the Polish perspective: design and first results of the Zabrze-Lipoprotein(a) Registry. Arch Med Sci 2024; 20: 1069-76.
5.
Burzyńska M, Jankowski P, Babicki M, Banach M, Chudzik M. Prevalence of hyperlipoproteinemia(a) in individuals of European ancestry treated at outpatient cardiology clinics: results from a cross-sectional STAR-Lp(a) study. Pol Arch Intern Med 2024; 134: 16860.
6.
Koren MJ, Moriarty PM, Baum SJ, et al. Preclinical development and phase 1 trial of a novel siRNA targeting lipoprotein(a). Nat Med 2022; 28: 96-103.
7.
Nissen SE, Wolski K, Cho L, et al. Lipoprotein(a) levels in a global population with established atherosclerotic cardiovascular disease. Open Heart 2022; 9: e002060.
8.
Björnson E, Adiels M, Taskinen MR, et al. Lipoprotein(a) is markedly more atherogenic than LDL. J Am Coll Cardiol 2024; 83: 385-95.
9.
Marston NA, Melloni GEM, Murphy SA, et al. Per-particle cardiovascular risk of lipoprotein(a) vs non-Lp(a) apolipoprotein B-containing lipoproteins. J Am Coll Cardiol 2024; 83: 470-2.
10.
Tsimikas S, Bittner V. Particle number and characteristics of lipoprotein(a), LDL, and apoB. J Am Coll Cardiol 2024; 83: 396-400.
11.
Strandkjær N, Hansen MK, Nielsen ST, et al. Lipoprotein(a) levels at birth and in early childhood: the COMPARE study. J Clin Endocrinol Metab 2022; 107: 324-35.
12.
Clarke SL, Huang RDL, Hilliard AT, et al. Genetically predicted lipoprotein(a) associates with coronary artery plaque severity independent of low-density lipoprotein cholesterol. Eur J Prev Cardiol 2025; 32: 116-27.
13.
Rocha VZ, Santos RD. The mysterious lipoprotein(a): moving towards further understanding of its atherogenic role. Eur J Prev Cardiol 2025; 32: 128-30.
14.
Boerwinkle E, Leffert CC, Lin J, Lackner C, Chiesa G, Hobbs HH. Apolipoprotein(a) gene accounts for greater than 90% of the variation in plasma lipoprotein(a) concentrations. J Clin Invest 1992; 90: 52-60.
15.
Burgess S, Ference BA, Staley JR, et al. Association of LPA variants with risk of coronary disease and the implications for lipoprotein(a)-lowering therapies: a Mendelian randomization analysis. JAMA Cardiol 2018; 3: 619-27.
16.
Lamina C, Kronenberg F, for the Lp(a)-GWAS-Consortium. Estimation of the required lipoprotein(a)-lowering therapeutic effect size for reduction in coronary heart disease outcomes: a Mendelian randomization analysis. JAMA Cardiol 2019; 4: 575-9.
17.
Schmidt K, Noureen A, Kronenberg F, Utermann G. Structure, function, and genetics of lipoprotein (a). J Lipid Res 2016; 57: 1339-59.
18.
Becker L, Cook PM, Wright TG, Koschinsky ML. Quantitative evaluation of the contribution of weak lysine-binding sites present within apolipoprotein(a) kringle IV types 6–8 to lipoprotein(a) assembly. J Biol Chem 2004; 279: 2679-88.
19.
Koschinsky ML, Beisiegel U, Henne-Bruns D, Eaton DL, Lawn RM. Apolipoprotein(a) size heterogeneity is related to variable number of repeat sequences in its mRNA. Biochemistry 1990; 29: 640-4.
20.
Kostner KM, Marz W, Kostner GM. When should we measure lipoprotein (a)? Eur Heart J 2013; 34: 3268-76.
21.
Kronenberg F, Utermann G. Lipoprotein(a): resurrected by genetics. J Intern Med 2013; 273: 6-30.
22.
Lobentanz E, Dieplinger H. Biogenesis of lipoprotein(a) in human and animal hepatocytes. Electrophoresis 1997; 18: 2677-81.
23.
Coassin S, Kronenberg F. Lipoprotein(a) beyond the kringle IV repeat polymorphism: the complexity of genetic variation in the LPA gene. Atherosclerosis 2022; 349: 17-35.
24.
Clarke R, Peden JF, Hopewell JC, et al. Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N Engl J Med 2009; 361: 2518-28.
25.
Koschinsky ML, Kronenberg F. The long journey of lipoprotein(a) from cardiovascular curiosity to therapeutic target. Atherosclerosis 2022; 349: 1-6.
26.
Banach M. Lipoprotein(a): the enemy that we still don’t know how to defeat. Eur Heart J Open 2023; 3: oead080.
27.
Boffa MB, Koschinsky ML. Lipoprotein (a): truly a direct prothrombotic factor in cardiovascular disease? J Lipid Res 2016; 57: 745-57.
28.
Boffa MB. Beyond fibrinolysis: the confounding role of Lp(a) in thrombosis. Atherosclerosis 2022; 349: 72-81.
29.
Lawn RM, Schwartz K, Patthy L. Convergent evolution of apolipoprotein(a) in primates and hedgehog. Proc Natl Acad Sci 1997; 94: 11992-7.
30.
Riches K, Porter KE. Lipoprotein(a): cellular effects and molecular mechanisms. Cholesterol 2012; 2012: 923289.
31.
Yano Y, Shimokawa K, Okada Y, Noma A. Immunolocalization of lipoprotein(a) in wounded tissues. J Histochem Cytochem 1997; 45: 559-68.
32.
Von Zychlinski A, Kleffmann T, Williams MJA, McCormick SP. Proteomics of lipoprotein(a) identifies a protein complement associated with response to wounding. J Proteomics 2011; 74: 2881-91.
33.
Tsimikas S. A test in context: lipoprotein(a). J Am Coll Cardiol 2017; 69: 692-711.
34.
Tsimikas S, Witztum JL. Oxidized phospholipids in cardiovascular disease. Nat Rev Cardiol 2024; 21: 170-91.
35.
Martínez C, Rivera J, Loyau S, et al. Binding of recombinant apolipoprotein(a) to human platelets and effect on platelet aggregation. Thromb Haemost 2001; 85: 686-93.
36.
Kamstrup PR, Neely RDG, Nissen S, et al. Lipoprotein(a) and cardiovascular disease: sifting the evidence to guide future research. Eur J Prev Cardiol 2024; 31: 903-14.
37.
Zimodro JM, Gąsecka A, Arski P, Schwarz J, Banach M, Gouni-Berthold I. Lipoprotein (a) measurement: potential for personalized cardiovascular disease management in a patient with acute myocardial infarction. Arch Med Sci 2024; 20: 1043-7.
38.
Page MM, Watts GF. Contemporary perspectives on the genetics and clinical use of lipoprotein(a) in preventive cardiology. Curr Opin Cardiol 2021; 36: 272-80.
39.
Reyes-Soffer G, Ginsberg HN, Berglund L, et al. Lipoprotein(a): a genetically determined, causal, and prevalent risk factor for atherosclerotic cardiovascular disease: a scientific statement from the American Heart Association. Arterioscler Thromb Vasc Biol 2022; 42: e48-60.
40.
Heydari M, Rezayi M, Ruscica M, Jamialahmadi T, Johnston TP, Sahebkar A. The ins and outs of lipoprotein(a) assay methods. Arch Med Sci Atheroscler Dis 2024; 8: 128-39.
41.
O’Donoghue ML, Rosenson RS, Gencer B, et al. Small interfering RNA to reduce lipoprotein(a) in cardiovascular disease. N Engl J Med 2022; 387: 1855-64.
42.
Clouet-Foraison N, Vaisar T, Marcovina SM. Standardization of analytical methods for the measurement of lipoprotein(a): bridging past and future initiatives. In: Lipoprotein(a) [Internet]. Kostner K, Kostner GM, Toth PP (eds.). Cham: Springer International Publishing 2023; 297-323. (Contemporary Cardiology).
43.
Swearingen CA, Sloan JH, Rhodes GM, et al. Measuring Lp(a) particles with a novel isoform-insensitive immunoassay illustrates efficacy of muvalaplin. J Lipid Res 2024; 66: 100723.
44.
Kronenberg F. Lipoprotein(a) measurement issues: are we making a mountain out of a molehill? Atherosclerosis 2022; 349: 123-35.
45.
Kronenberg F, Mora S, Stroes ESG, et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. Eur Heart J 2022; 43: 3925-46.
46.
Ruhaak LR, Cobbaert CM. Quantifying apolipoprotein(a) in the era of proteoforms and precision medicine. Clin Chim Acta 2020; 511: 260-8.
47.
Szarek M, Reijnders E, Jukema JW, et al. Relating lipoprotein(a) concentrations to cardiovascular event risk after acute coronary syndrome: a comparison of 3 tests. Circulation 2024; 149: 192-203.
48.
Johansen AK, Bogsrud MP, Thoresen M, et al. Lipoprotein(a) in children and adolescents with genetically confirmed familial hypercholesterolemia followed up at a specialized lipid clinic. Atheroscler Plus 2024; 57: 13-8.
49.
Simony SB, Mortensen MB, Langsted A, Afzal S, Kamstrup PR, Nordestgaard BG. Sex differences of lipoprotein(a) levels and associated risk of morbidity and mortality by age: The Copenhagen General Population Study. Atherosclerosis 2022; 355: 76-82.
50.
Corral P, Matta MG, Aguilar-Salinas C, et al. Lipoprotein(a) throughout life in women. Am J Prev Cardiol 2024; 20: 100885.
51.
Sattar N, Clark P, Greer IA, Shepherd J, Packard CJ. Lipoprotein (a) levels in normal pregnancy and in pregnancy complicated with pre-eclampsia. Atherosclerosis 2000; 148: 407-11.
52.
Wang Q, Würtz P, Auro K, et al. Metabolic profiling of pregnancy: cross-sectional and longitudinal evidence. BMC Med 2016; 14: 205.
53.
Manten GTR, Franx A, Van Der Hoek YY, et al. Changes of plasma lipoprotein(a) during and after normal pregnancy in Caucasians. J Matern Fetal Neonatal Med 2003; 14: 91-5.
54.
Lewek J, Bielecka-Dąbrowa A, Toth PP, Banach M. Dyslipidaemia management in pregnant patients: a 2024 update. Eur Heart J Open 2024; 4: oeae032.
55.
Golawski M, Lejawa M, Osadnik T, et al. Genetically determined lipoprotein(a) levels do not cause an increased risk of preeclampsia – a two-sample Mendelian randomization study. Eur Heart J 2023; 44 (Suppl. 2): ehad655.2728.
56.
Sosnowska B, Stepinska J, Mitkowski P, et al. Recommendations of the Experts of the Polish Cardiac Society (PCS) and the Polish Lipid Association (PoLA) on the diagnosis and management of elevated lipoprotein(a) levels. Arch Med Sci 2024; 20: 8-27.
57.
Enkhmaa B, Berglund L. Non-genetic influences on lipoprotein(a) concentrations. Atherosclerosis 2022; 349: 53-62.
58.
Surma S, Sahebkar A, Banach M, endorsed by the International Lipid Expert Panel (ILEP). Low carbohydrate/ketogenic diet in the optimization of lipoprotein(a) levels: do we have sufficient evidence for any recommendation? Eur Heart J 2023; 44: 4904-6.
59.
Gaba P, Rosenson RS, López JAG, et al. Intraindividual variability in serial lipoprotein(a) concentrations among placebo-treated patients in the OCEAN(a)-DOSE trial. J Am Coll Cardiol 2025; 85: 550-3.
60.
Harb T, Ziogos E, Blumenthal RS, Gerstenblith G, Leucker TM. Intra-individual variability in lipoprotein(a): the value of a repeat measure for reclassifying individuals at intermediate risk. Eur Heart J Open 2024; 4: oeae064.
61.
Moriarty PM, Gorby LK, Stroes ES, Kastelein JP, Davidson M, Tsimikas S. Lipoprotein(a) and its potential association with thrombosis and inflammation in COVID-19: a testable hypothesis. Curr Atheroscler Rep 2020; 22: 48.
62.
Müller N, Schulte DM, Türk K, et al. IL-6 blockade by monoclonal antibodies inhibits apolipoprotein (a) expression and lipoprotein (a) synthesis in humans. J Lipid Res 2015; 56: 1034-42.
63.
Surma S, Sosnowska B, Reiner Ž, Banach M. New data allow to better understand the secrets of lipoprotein(a): is that for sure? Eur Heart J Open 2024; 4: oeae066.
64.
Sourij C, Aziz F, Krappinger S, et al. Changes in lipoprotein(a) levels in people after ST elevation myocardial infarction – the STEMI-Lipids Study. Int J Mol Sci 2023; 24: 15531.
65.
Ziogos E, Vavuranakis MA, Harb T, et al. Lipoprotein(a) concentrations in acute myocardial infarction patients are not indicative of levels at six month follow-up. Eur Heart J Open 2023; 3: oead035.
66.
Barth JH, Jackson BM, Farrin AJ, et al.; SPACE ROCKET Trial Group. Change in serum lipids after acute coronary syndromes: secondary analysis of SPACE ROCKET study data and a comparative literature review. Clin Chem 2010; 56: 1592-8.
67.
Chiesa G, Zenti MG, Baragetti A, et al. Consensus document on lipoprotein(a) from the Italian Society for the Study of Atherosclerosis (SISA). Nutr Metab Cardiovasc Dis 2023; 33: 1866-77.
68.
Durlach V, Bonnefont-Rousselot D, Boccara F, et al. Lipoprotein(a): pathophysiology, measurement, indication and treatment in cardiovascular disease. A consensus statement from the Nouvelle Société Francophone d’Athérosclérose (NSFA). Arch Cardiovasc Dis 2021; 114: 828-47.
69.
Pearson GJ, Thanassoulis G, Anderson TJ, et al. 2021 Canadian Cardiovascular Society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in adults. Can J Cardiol 2021; 37: 1129-50.
70.
Puri R, Nissen SE, Arsenault BJ, et al. Effect of C-reactive protein on lipoprotein(a)-associated cardiovascular risk in optimally treated patients with high-risk vascular disease: a prespecified secondary analysis of the ACCELERATE trial. JAMA Cardiol 2020; 5: 1136-43.
71.
Li JJ, Ma CS, Zhao D, et al. Lipoprotein(a) and cardiovascular disease in Chinese population. JACC Asia 2022; 2: 653-65.
72.
Koschinsky ML, Bajaj A, Boffa MB, et al. A focused update to the 2019 NLA scientific statement on use of lipoprotein(a) in clinical practice. J Clin Lipidol 2024; 18: e308-19.
73.
Loh WJ, Pang J, Chakraborty A, et al. Cascade testing of children and adolescents for elevated Lp(a) in pedigrees with familial hypercholesterolaemia. J Clin Lipidol 2024; 18: e33-7.
74.
Patel AP, Wang M, Pirruccello JP, et al. Lp(a) (lipoprotein[a]) concentrations and incident atherosclerotic cardiovascular disease: new insights from a large National Biobank. Arterioscler Thromb Vasc Biol 2021; 41: 465-74.
75.
Kamstrup PR. Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA 2009; 301: 2331.
76.
Burzynska M, Babicki M, Banach M, Jankowski P, Chudzik M. Lipoprotein(a) as a predictive marker of coronary artery calcification (CAC). The results from the STAR-Lp(a) cohort study. Eur Heart J 2024; 45 (Suppl. 1): ehae666.2829.
77.
Bhatia HS, Hurst S, Desai P, Zhu W, Yeang C. Lipoprotein(a) testing trends in a large academic health system in the United States. J Am Heart Assoc 2023; 12: e031255.
78.
Zafrir B, Aker A, Saliba W. Lipoprotein(a) testing in clinical practice: real-life data from a large healthcare provider. Eur J Prev Cardiol 2022; 29: e331-3.
79.
Nurmohamed NS, Kaiser Y, Schuitema PCE, et al. Finding very high lipoprotein(a): the need for routine assessment. Eur J Prev Cardiol 2022; 29: 769-76.
80.
Thanassoulis G, Campbell CY, Owens DS, et al. Genetic associations with valvular calcification and aortic stenosis. N Engl J Med 2013; 368: 503-12.
81.
Langsted A, Nordestgaard BG, Kamstrup PR. Elevated lipoprotein(a) and risk of ischemic stroke. J Am Coll Cardiol 2019; 74: 54-66.
82.
Masson W, Lobo M, Barbagelata L, Molinero G, Bluro I, Nogueira JP. Elevated lipoprotein (a) levels and risk of peripheral artery disease outcomes: a systematic review. Vasc Med 2022; 27: 385-91.
83.
Kamstrup PR, Nordestgaard BG. Elevated lipoprotein(a) levels, LPA risk genotypes, and increased risk of heart failure in the general population. JACC Heart Fail 2016; 4: 78-87.
84.
Lewek J, Sosnowska B, Bielecka-Dąbrowa A, Mierczak K, Adach W, Banach M. Lipoprotein(a) and other risk factors in dyslipidemic patients with and without heart failure. Arch Med Sci 2024; 20: 1705-9.
85.
Singh S, Baars DP, Desai R, Singh D, Pinto-Sietsma SJ. Association between lipoprotein(a) and risk of atrial fibrillation: a systematic review and meta-analysis of Mendelian randomization studies. Curr Probl Cardiol 2024; 49: 102024.
86.
Grant JK, Martin SS, Zhang S, et al. Racial differences in the burden of atherosclerotic cardiovascular disease related to elevated lipoprotein(a) levels: the ARIC study. Circulation 2024; 150: 250-2.
87.
Ridker PM, Moorthy MV, Cook NR, Rifai N, Lee IM, Buring JE. Inflammation, cholesterol, lipoprotein(a), and 30-year cardiovascular outcomes in women. N Engl J Med 2024; 391: 2087-97.
88.
Bhatia HS, Wandel S, Willeit P, et al. Independence of lipoprotein(a) and low-density lipoprotein cholesterol-mediated cardiovascular risk: a participant-level meta-analysis. Circulation 2025; 151: 312-21.
90.
Small AM, Pournamdari A, Melloni GEM, et al. Lipoprotein(a), C-reactive protein, and cardiovascular risk in primary and secondary prevention populations. JAMA Cardiol 2024; 9: 385.
91.
Thomas PE, Vedel-Krogh S, Kamstrup PR, Nordestgaard BG. Lipoprotein(a) is linked to atherothrombosis and aortic valve stenosis independent of C-reactive protein. Eur Heart J 2023; 44: 1449-60.
92.
Arnold N, Blaum C, Goßling A, et al. C-reactive protein modifies lipoprotein(a)-related risk for coronary heart disease: the BiomarCaRE project. Eur Heart J 2024; 45: 1043-54.
93.
Zhang W, Speiser JL, Ye F, et al. High-sensitivity C-reactive protein modifies the cardiovascular risk of lipoprotein(a). J Am Coll Cardiol 2021; 78: 1083-94.
94.
Yuan D, Wang P, Jia S, et al. Lipoprotein(a), high-sensitivity C-reactive protein, and cardiovascular risk in patients undergoing percutaneous coronary intervention. Atherosclerosis 2022; 363: 109-16.
95.
Alebna PL, Han CY, Ambrosio M, et al. Association of lipoprotein(a) with major adverse cardiovascular events across hs-CRP. JACC Adv 2024; 3: 101409.
96.
Chung YH, Lee BK, Kwon HM, et al. Coronary calcification is associated with elevated serum lipoprotein (a) levels in asymptomatic men over the age of 45 years: a cross-sectional study of the Korean national health checkup data. Medicine (Baltimore) 2021; 100: e24962.
97.
Mehta A, Vasquez N, Ayers CR, et al. Independent association of lipoprotein(a) and coronary artery calcification with atherosclerotic cardiovascular risk. J Am Coll Cardiol 2022; 79: 757-68.
98.
Kaiser Y, Daghem M, Tzolos E, et al. Association of lipoprotein(a) with atherosclerotic plaque progression. J Am Coll Cardiol 2022; 79: 223-33.
99.
Qiu Y, Hao W, Guo Y, et al. The association of lipoprotein (a) with coronary artery calcification: a systematic review and meta-analysis. Atherosclerosis 2024; 388: 117405.
100.
Zheng KH, Tsimikas S, Pawade T, et al. Lipoprotein(a) and oxidized phospholipids promote valve calcification in patients with aortic stenosis. J Am Coll Cardiol 2019; 73: 2150-62.
101.
Khan MI, Zahir RS, Dominguez AC, Romeo FJ. Role of Lipoprotein (A) in aortic valve stenosis: novel disease mechanisms and emerging pharmacotherapeutic approaches. IJC Heart Vasc 2024; 55: 101543.
102.
Arsenault BJ, Loganath K, Girard A, et al. Lipoprotein(a) and calcific aortic valve stenosis progression: a systematic review and meta-analysis. JAMA Cardiol 2024; 9: 835-42.
103.
Surma S, Zembala MO, Okopień B, Banach M. Lipoprotein (a) and lipid-lowering treatment from the perspective of a cardiac surgeon. An impact on the prognosis in patients with aortic valve replacement and after heart transplantation. Int J Cardiol Cardiovasc Risk Prev 2024; 22: 200297.
104.
Kim AR, Ahn JM, Kang DY, et al. Association of lipoprotein(a) with severe degenerative aortic valve stenosis. JACC Asia 2024; 4: 751-60.
105.
Tsimikas S. Lp(a) and accelerated progression of aortic stenosis. JACC Asia 2024; 4: 761-3.
106.
Wu B, Zhang Z, Long J, Zhao H, Zeng F. Association between lipoprotein (a) and heart failure with reduced ejection fraction development. J Clin Lab Anal 2022; 36: e24083.
107.
Singh S, Baars DP, Aggarwal K, Desai R, Singh D, Pinto-Sietsma SJ. Association between lipoprotein (a) and risk of heart failure: a systematic review and meta-analysis of Mendelian randomization studies. Curr Probl Cardiol 2024; 49: 102439.
108.
Januzzi JL, Van Kimmenade RRJ, Liu Y, et al. Lipoprotein(a), oxidized phospholipids, and progression to symptomatic heart failure: the CASABLANCA study. J Am Heart Assoc 2024; 13: e034774.
109.
Zheng W, Chilazi M, Park J, et al. Assessing the accuracy of estimated lipoprotein(a) cholesterol and lipoprotein(a)-free low-density lipoprotein cholesterol. J Am Heart Assoc 2022; 11: e023136.
110.
Solnica B, Sygitowicz G, Sitkiewicz D, et al. 2024 Guidelines of the Polish Society of Laboratory Diagnostics and the Polish Lipid Association on laboratory diagnostics of lipid metabolism disorders. Arch Med Sci 2024; 20: 357-74.
111.
Arnold N, Blaum C, Goßling A, et al. Impact of lipoprotein(a) level on low-density lipoprotein cholesterol– or apolipoprotein b–related risk of coronary heart disease. J Am Coll Cardiol 2024; 84: 165-77.
112.
Tsimikas S, Yeang C, Kronenberg F. In search of an accurate measurement of LDL-C. J Am Coll Cardiol 2024; 84: 178-81.
113.
Banach M, Surma S, Toth PP; endorsed by the International Lipid Expert Panel (ILEP). 2023: The year in cardiovascular disease – the year of new and prospective lipid lowering therapies. Can we render dyslipidemia a rare disease by 2024? Arch Med Sci 2023; 19: 1602-15.
114.
Banach M, Burchardt P, Chlebus K, et al. PoLA/CFPiP/PCS/PSLD/PSD/PSH guidelines on diagnosis and therapy of lipid disorders in Poland 2021. Arch Med Sci 2021; 17: 1447-547.
115.
Yahya R, Berk K, Verhoeven A, et al. Statin treatment increases lipoprotein(a) levels in subjects with low molecular weight apolipoprotein(a) phenotype. Atherosclerosis 2019; 289: 201-5.
116.
Tsimikas S, Gordts PLSM, Nora C, Yeang C, Witztum JL. Statin therapy increases lipoprotein(a) levels. Eur Heart J 2020; 41: 2275-84.
117.
Banach M, Penson PE. Statins and Lp(a): do not make perfect the enemy of excellent. Eur Heart J 2020; 41: 190-1.
118.
Banach M, Surma S, Kapłon-Cieślicka A, et al. Position paper of the Polish Expert Group on the use of pitavastatin in the treatment of lipid disorders in Poland endorsed by the Polish Lipid Association. Arch Med Sci 2024; 20: 28-42.
119.
Sahebkar A, Simental-Mendía LE, Pirro M, et al. Impact of ezetimibe on plasma lipoprotein(a) concentrations as monotherapy or in combination with statins: a systematic review and meta-analysis of randomized controlled trials. Sci Rep 2018; 8: 17887.
120.
Awad K, Mikhailidis DP, Katsiki N, Muntner P, Banach M. Effect of ezetimibe monotherapy on plasma lipoprotein(a) concentrations in patients with primary hypercholesterolemia: a systematic review and meta-analysis of randomized controlled trials. Drugs 2018; 78: 453-62.
121.
Ridker PM, Lei L, Ray KK, Ballantyne CM, Bradwin G, Rifai N. Effects of bempedoic acid on CRP, IL-6, fibrinogen and lipoprotein(a) in patients with residual inflammatory risk: a secondary analysis of the CLEAR harmony trial. J Clin Lipidol 2023; 17: 297-302.
122.
Chemello K, Chan DC, Lambert G, Watts GF. Recent advances in demystifying the metabolism of lipoprotein(a). Atherosclerosis 2022; 349: 82-91.
123.
The HPS2-THRIVE Collaborative Group. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med 2014; 371: 203-12.
124.
Haynes R, Valdes-Marquez E, Hopewell JC, et al. Serious adverse effects of extended-release niacin/laropiprant: results from the Heart Protection Study 2–Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) Trial. Clin Ther 2019; 41: 1767-77.
125.
O’Donoghue ML, Fazio S, Giugliano RP, et al. Lipoprotein(a), PCSK9 inhibition, and cardiovascular risk: insights from the FOURIER Trial. Circulation 2019; 139: 1483-92.
126.
Bittner VA, Szarek M, Aylward PE, et al. Effect of alirocumab on lipoprotein(a) and cardiovascular risk after acute coronary syndrome. J Am Coll Cardiol 2020; 75: 133-44.
127.
Toth PP, Jones SR, Monsalvo ML, Elliott-Davey M, López JAG, Banach M. Effect of evolocumab on non-high-density lipoprotein cholesterol, apolipoprotein b, and lipoprotein(a): a pooled analysis of phase 2 and phase 3 studies. J Am Heart Assoc 2020; 9: e014129.
128.
Ray KK, Kallend D, Leiter LA, et al. Effect of inclisiran on lipids in primary prevention: the ORION-11 trial. Eur Heart J 2022; 43: 5047-57.
129.
Katsiki N, Vrablik M, Banach M, Gouni-Berthold I. Inclisiran, low-density lipoprotein cholesterol and lipoprotein (a). Pharmaceuticals (Basel) 2023; 16: 577.
130.
Blanchard V, Chemello K, Hollstein T, et al. The size of apolipoprotein (a) is an independent determinant of the reduction in lipoprotein (a) induced by PCSK9 inhibitors. Cardiovasc Res 2022; 118: 2103-11.
131.
Akinlonu A, Boffa MB, Lyu C, et al. Variation in lipoprotein(a) response to potent lipid lowering: the role of apolipoprotein (a) isoform size. J Clin Lipidol 2025; 19: 39-50.
132.
Connelly‐Smith L, Alquist CR, Aqui NA, et al. Guidelines on the use of therapeutic apheresis in clinical practice – evidence‐based approach from the writing committee of the American Society for Apheresis: the ninth special issue. J Clin Apheresis 2023; 38: 77-278.
133.
Safarova MS, Moriarty PM. Lipoprotein apheresis: current recommendations for treating familial hypercholesterolemia and elevated lipoprotein(a). Curr Atheroscler Rep 2023; 25: 391-404.
134.
Waldmann E, Parhofer KG. Lipoprotein apheresis to treat elevated lipoprotein (a). J Lipid Res 2016; 57: 1751-7.
135.
Stefanutti C, Mazza F, Pasqualetti D, et al. Lipoprotein apheresis downregulates IL-1, IL-6 and TNF- mRNA expression in severe dyslipidaemia. Atheroscler Suppl 2017; 30: 200-8.
136.
Leebmann J, Roeseler E, Julius U, et al. Lipoprotein apheresis in patients with maximally tolerated lipid-lowering therapy, lipoprotein(a)-hyperlipoproteinemia, and progressive cardiovascular disease: prospective observational multicenter study. Circulation 2013; 128: 2567-76.
137.
Lipoprotein Apheresis: First FDA Indicated Treatment for Elevated Lipoprotein(a). J Clin Cardiol [Internet]. 15 październik 2020 [cytowane 8 styczeń 2025];1(1). Available: https://www.scientificarchives....
138.
Kayikcioglu M. LDL Apheresis and Lp (a) apheresis: a clinician’s perspective. Curr Atheroscler Rep 2021; 23: 15.
139.
The ASCEND Study Collaborative Group. Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med 2018; 379: 1529-39.
140.
Gaziano JM, Brotons C, Coppolecchia R, et al. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial. Lancet 2018; 392: 1036-46.
141.
McNeil JJ, Wolfe R, Woods RL, et al. Effect of aspirin on cardiovascular events and bleeding in the healthy elderly. N Engl J Med 2018; 379: 1509-18.
142.
Zheng SL, Roddick AJ. Association of aspirin use for primary prevention with cardiovascular events and bleeding events: a systematic review and meta-analysis. JAMA 2019; 321: 277-87.
143.
Lacaze P, Bakshi A, Riaz M, et al. Aspirin for primary prevention of cardiovascular events in relation to lipoprotein(a) genotypes. J Am Coll Cardiol 2022; 80: 1287-98.
144.
Bhatia HS, Trainor P, Carlisle S, et al. Aspirin and cardiovascular risk in individuals with elevated lipoprotein(a): the multi‐ethnic study of atherosclerosis. J Am Heart Assoc 2024; 13: e033562.
145.
Chasman DI, Shiffman D, Zee RYL, et al. Polymorphism in the apolipoprotein(a) gene, plasma lipoprotein(a), cardiovascular disease, and low-dose aspirin therapy. Atherosclerosis 2009; 203: 371-6.
146.
Razavi AC, Richardson LC, Coronado F, et al. Aspirin use for primary prevention among US adults with and without elevated lipoprotein(a). Am J Prev Cardiol 2024; 18: 100674.
147.
Patel SM, Bonaca MP, Morrow DA, et al. Lipoprotein(a) and benefit of antiplatelet therapy: insights from the PEGASUS-TIMI 54 Trial. JACC Adv 2023; 2: 100675.
148.
Della Bona R, Giubilato S, Palmieri M, et al. Aspirin in primary prevention: looking for those who enjoy it. J Clin Med 2024; 13: 4148.
149.
Banach M, Surma S, Bielecka-Dąbrowa A, et al. Rosuvastatin-based combination treatment with acetylsalicylic acid or ezetimibe in the management of patients at high and very high cardiovascular risk. Expert opinion paper of the Polish Lipid Association 2025. Arch Med Sci 2025; 21: 1-15.
150.
Sosnowska B, Surma S, Banach M. Targeted treatment against lipoprotein (a): the coming breakthrough in lipid lowering therapy. Pharmaceuticals 2022; 15: 1573.
151.
O’Donoghue ML, Rosenson RS, López JAG, et al. The off-treatment effects of olpasiran on lipoprotein(a) lowering. J Am Coll Cardiol 2024; 84: 790-7.
152.
Nissen SE, Wang Q, Nicholls SJ, et al. Zerlasiran – a small-interfering RNA targeting lipoprotein(a): a phase 2 randomized clinical trial. JAMA 2024; 332: 1992.
153.
Nissen SE, Linnebjerg H, Shen X, et al. Lepodisiran, an extended-duration short interfering RNA targeting lipoprotein(a): a randomized dose-ascending clinical trial. JAMA 2023; 330: 2075-83.
154.
Kulkarni JA, Witzigmann D, Thomson SB, et al. The current landscape of nucleic acid therapeutics. Nat Nanotechnol 2021; 16: 630-43.
155.
Novartis Pharmaceuticals. A Randomized Double-blind, Placebo-controlled, Multicenter Trial Assessing the Impact of Lipoprotein (a) Lowering With Pelacarsen (TQJ230) on Major Cardiovascular Events in Patients With Established Cardiovascular Disease [Internet]. clinicaltrials.gov; 2025 [accessed 12 January 2025]. Report No.: NCT04023552. Available at: https://clinicaltrials.gov/stu....
156.
Novartis Pharmaceuticals. A Randomized Double-blind, Placebo-controlled, Multicenter Trial Assessing the Impact of Lipoprotein(a) Lowering With Pelacarsen (TQJ230) on the Progression of Calcific Aortic Valve Stenosis [Lp(a)FRONTIERS CAVS] [Internet]. clinicaltrials.gov; 2024 [accessed 12 January 2025]. Report No.: NCT05646381. Available at: https://clinicaltrials.gov/stu....
157.
Amgen. A Double-blind, Randomized, Placebo-controlled, Multicenter Study Assessing the Impact of Olpasiran on Major Cardiovascular Events in Participants With Atherosclerotic Cardiovascular Disease and Elevated Lipoprotein(a) [Internet]. clinicaltrials.gov; 2024 [accessed 12 January 2025]. Report No.: NCT05581303. Available at: https://clinicaltrials.gov/stu....
158.
Eli Lilly and Company. A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of LY3819469 in Adults With Elevated Lipoprotein(a) [Internet]. clinicaltrials.gov; 2025 [accessed 12 January 2025]. Report No.: NCT05565742. Available at: https://clinicaltrials.gov/stu....
159.
Eli Lilly and Company. A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Effect of Lepodisiran on the Reduction of Major Adverse Cardiovascular Events in Adults With Elevated Lipoprotein(a) Who Have Established Atherosclerotic Cardiovascular Disease or Are at Risk for a First Cardiovascular Event - ACCLAIM-Lp(a) [Internet]. clinicaltrials.gov; 2024 [accessed 12 January 2025]. Report No.: NCT06292013. Available at: https://clinicaltrials.gov/stu....
160.
Nicholls SJ, Nissen SE, Fleming C, et al. Muvalaplin, an oral small molecule inhibitor of lipoprotein(a) formation: a randomized clinical trial. JAMA 2023; 330: 1042.
161.
Morrow PK, D’Souza S, Wood T, et al. Abstract 17013: CTX320: An Investigational in vivo CRISPR-Based Therapy Efficiently and Durably Reduces Lipoprotein (a) Levels in Non-Human Primates After a Single Dose. Circulation 2023; 148 (Suppl_1). https://www.ahajournals.org/do....
162.
Nicholls SJ. Therapeutic potential of lipoprotein(a) inhibitors. Drugs 2024; 84: 637-43.
163.
Nicholls SJ, Ni W, Rhodes GM, et al. Oral muvalaplin for lowering of lipoprotein(a): a randomized clinical trial. JAMA 2025; 333: 222-31.
164.
CTX320: An Investigational In Vivo CRISPR-Based Therapy Efficiently And Durably Reduces Lipoprotein(a) Levels In Non-Human Primates After A Single Dose. [Internet]. Available at: https://ir.crisprtx.com/static....
165.
Nicholls SJ, Ditmarsch M, Kastelein JJ, et al. Lipid lowering effects of the CETP inhibitor obicetrapib in combination with high-intensity statins: a randomized phase 2 trial. Nat Med 2022; 28: 1672-8.
166.
Tsimikas S, Yang X, Hsieh A, Ditmarsch M, Davidson M, Kastelein J. Obicetrapib demonstrates significant reductions of Lp(a) on top of high-intensity statins. Atherosclerosis 2024; 395: 118412.
167.
Nicholls S, Nelson A, Ditmarsch M, et al. 4171281 Safety and efficacy of obicetrapib in patients with heterozygous familial hypercholesterolemia. Circulation 2024; 150: https://doi.org/10.1161/CIR.00....
168.
NewAmsterdam Pharma. A Phase 2 Study to Evaluate the Effect of Obicetrapib Alone and in Combination With Evolocumab (Repatha®) on Lipoprotein (a) in Patients With Mild Dyslipidemia: The VINCENT Study [Internet]. clinicaltrials.gov; 2024 lis [accessed January 2025]. Report No.: NCT06496243. Available at: https://clinicaltrials.gov/stu....
169.
Gudbjartsson DF, Thorgeirsson G, Sulem P, et al. Lipoprotein(a) concentration and risks of cardiovascular disease and diabetes. J Am Coll Cardiol 2019; 74: 2982-94.
170.
Kamstrup PR, Nordestgaard BG. Lipoprotein(a) concentrations, isoform size, and risk of type 2 diabetes: a Mendelian randomisation study. Lancet Diabetes Endocrinol 2013; 1: 220-7.
171.
Paige E, Masconi KL, Tsimikas S, et al. Lipoprotein(a) and incident type-2 diabetes: results from the prospective Bruneck study and a meta-analysis of published literature. Cardiovasc Diabetol 2017; 16: 38.
172.
Tsimikas S. In search of a physiological function of lipoprotein(a): causality of elevated Lp(a) levels and reduced incidence of type 2 diabetes. J Lipid Res 2018; 59: 741-4.
173.
Farukhi ZM, Mora S. Lifelong low Lp(a) levels: genetics give a green light? Eur Heart J 2021; 42: 1157-9.
174.
Ye Z, Haycock PC, Gurdasani D, et al. The association between circulating lipoprotein(a) and type 2 diabetes: is it causal? Diabetes 2014; 63: 332-42.
175.
Goławski M, Lejawa M, Banach M, Jóźwiak J, Gierlotka M, Osadnik T. Association between Lp(a) and T2D: a Mendelian randomization study. Arch Med Sci 2024; 20: 1002-5.
176.
Yeung MW, Said MA, Van De Vegte YJ, Verweij N, Dullaart RPF, Van Der Harst P. Associations of very low lipoprotein(a) levels with risks of new-onset diabetes and non-alcoholic liver disease. Atheroscler Plus 2024; 57: 19-25.
177.
Lejawa M, Goławski M, Fronczek M, et al. Causal associations between insulin and Lp(a) levels in Caucasian population: a Mendelian randomization study. Cardiovasc Diabetol 2024; 23: 316.
178.
Sabouret P, Dib J, Ecarnot F, Banach M, Lellouche N. Eligibility for icosapent ethyl in a French population of coronary outpatients with type 2 diabetes. Arch Med Sci 2023; 19: 1901-3.
179.
Konieczyńska M, Natorska J, Ząbczyk M, Undas A. Lipoprotein(a) and thromboembolism: current state of knowledge and unsolved issues. Arch Med Sci 2024; 20: 1770-83.
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