References
- Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139(25):e1082–e1143. DOI: 10.1161/CIR.0000000000000625
- Kronenberg F, Mora S, Stroes ESG, Ference BA, Arsenault BJ, Berglund L, et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: A European Atherosclerosis Society consensus statement. Eur Heart J. 2022;43(39):3925–3946. DOI: 10.1093/eurheartj/ehac361
- Tsimikas S, Marcovina SM. Ancestry, lipoprotein(a), and cardiovascular risk thresholds: JACC review topic of the week. J Am Coll Cardiol. 2022;80(9):934–946. DOI: 10.1016/j.jacc.2022.06.019
- Melita H, Manolis AA, Manolis TA, Manolis AS. Lipoprotein(a) and cardiovascular disease: A missing link for premature atherosclerotic heart disease and/or residual risk. J Cardiovasc Pharmacol. 2022;79(1):e18–e35. DOI: 10.1097/FJC.0000000000001160
- Tsimikas S, Fazio S, Ferdinand KC, Ginsberg HN, Koschinsky ML, Marcovina SM, et al. NHLBI Working Group recommendations to reduce lipoprotein(a)-mediated risk of cardiovascular disease and aortic stenosis. J Am Coll Cardiol. 2018;71(2):177–192. DOI: 10.1016/j.jacc.2017.11.014
- Rehberger Likozar A, Zavrtanik M, Sebestjen M. Lipoprotein(a) in atherosclerosis: From pathophysiology to clinical relevance and treatment options. Ann Med. 2020;52(5):162–177. DOI: 10.1080/07853890.2020.1775287
- Bjornson E, Adiels M, Taskinen MR, Burgess S, Chapman MJ, Packard CJ, et al. Lipoprotein(a) is markedly more atherogenic than LDL: An apolipoprotein B-based genetic analysis. J Am Coll Cardiol. 2024;83(3):385–395. DOI: 10.1016/j.jacc.2023.10.039
- Willeit P, Ridker PM, Nestel PJ, Simes J, Tonkin AM, Pedersen TR, et al. Baseline and on-statin treatment lipoprotein(a) levels for prediction of cardiovascular events: Individual patient-data meta-analysis of statin outcome trials. Lancet. 2018;392(10155):1311–1320. DOI: 10.1016/S0140-6736(18)31652-0
- Berman AN, Biery DW, Besser SA, Singh A, Shiyovich A, Weber BN, et al. Lipoprotein(a) and major adverse cardiovascular events in patients with or without baseline atherosclerotic cardiovascular disease. J Am Coll Cardiol. 2024;83(9):873–886. DOI: 10.1016/j.jacc.2023.12.031
- Wong ND, Fan W, Hu X, Ballantyne C, Hoodgeveen RC, Tsai MY, et al. Lipoprotein(a) and long-term cardiovascular risk in a multi-ethnic pooled prospective cohort. J Am Coll Cardiol. 2024;83(16):1511–1525. DOI: 10.1016/j.jacc.2024.02.031
- Bhatia HS, Wandel S, Willeit P, Lesogor A, Bailey K, Ridker PM, et al. Independence of lipoprotein(a) and low-density lipoprotein cholesterol-mediated cardiovascular risk: A participant-level meta-analysis. Circulation. 2025;151(4):312–321. DOI: 10.1161/CIRCULATIONAHA.124.069556
- Wang Z, Tang J, Shi Q, Fang L, Liu N, Zhang J. Synergistic effect of lipoprotein(a) and high-sensitivity C-reactive protein on the risk of all-cause and cardiovascular death in patients with acute myocardial infarction: A large prospective cohort study. Front Endocrinol (Lausanne). 2024;15:
1392859 . DOI: 10.3389/fendo.2024.1392859 - Boffa MB, Koschinsky ML. Oxidized phospholipids as a unifying theory for lipoprotein(a) and cardiovascular disease. Nat Rev Cardiol. 2019;16(5):305–318. DOI: 10.1038/s41569-018-0153-2
- Katkenov N, Mukhatayev Z, Kozhakhmetov S, Sailybayeva A, Bekbossynova M, Kushugulova A. Systematic review on the role of IL-6 and IL-1 beta in cardiovascular diseases. J Cardiovasc Dev Dis. 2024;11(7):
206 . DOI: 10.3390/jcdd11070206 - Zhang W, Speiser JL, Ye F, Tsai MY, Cainzos-Achirica M, Nasir K, et al. High-sensitivity C-reactive protein modifies the cardiovascular risk of lipoprotein(a): Multi-ethnic study of atherosclerosis. J Am Coll Cardiol. 2021;78(11):1083–1094. DOI: 10.1016/j.jacc.2021.07.016
- Mensah GA, Arnold N, Prabhu SD, Ridker PM, Welty FK. Inflammation and Cardiovascular Disease: 2025 ACC Scientific Statement: A Report of the American College of Cardiology. J Am Coll Cardiol. Published online September 29, 2025. DOI: 10.1016/j.jacc.2025.08.047
- Pearson GJ, Thanassoulis G, Anderson TJ, Barry AR, Couture P, Dayan N, 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(8):1129–1150. DOI: 10.1016/j.cjca.2021.03.016
- Koschinsky ML, Bajaj A, Boffa MB, Dixon DL, Ferdinand KC, Gidding SS, et al. A focused update to the 2019 NLA Scientific Statement on Use of Lipoprotein(a) in Clinical Practice. J Clin Lipidol. 2024;18(3):e308–e319. DOI: 10.1016/j.jacl.2024.03.001
- Shapiro MD, Haddad TM, Weintraub HS, Baum SJ, Abdul-Nour K, Sarwat S, et al. Lipoprotein(a) levels in a population with clinical atherosclerotic cardiovascular disease in the United States: A subanalysis from the Lp(a)HERITAGE study. J Clin Lipidol. 2025;19(1):28–38. DOI: 10.1016/j.jacl.2024.11.007
- Nissen SE, Wolski K, Cho L, Nicholls SJ, Kastelein J, Leitersdorf E, et al. Lipoprotein(a) levels in a global population with established atherosclerotic cardiovascular disease. Open Heart. 2022;9(2):
e002060 . DOI: 10.1136/openhrt-2022-002060 - Tian X, Zhang N, Tse G, Li G, Sun Y, Liu T. Association between lipoprotein(a) and premature atherosclerotic cardiovascular disease: A systematic review and meta-analysis. Eur Heart J Open. 2024;4(3):
oeae031 . DOI: 10.1093/ehjopen/oeae031 - Rallidis LS, Pavlakis G, Foscolou A, Kotakos C, Katsimardos A, Drosatos A, et al. High levels of lipoprotein (a) and premature acute coronary syndrome. Atherosclerosis. 2018;269:29–34. DOI: 10.1016/j.atherosclerosis.2017.12.011
- Yu MM, Wang ML, Wang JJ, Lin BL, Zhao X, Tao XW, et al. Association of lipoprotein(a) levels with myocardial infarction in patients with low-attenuation plaque. J Am Coll Cardiol. 2024;83(18):1743–1755. DOI: 10.1016/j.jacc.2024.03.367
- Thomas IC, Forbang NI, Criqui MH. The evolving view of coronary artery calcium and cardiovascular disease risk. Clin Cardiol. 2018;41(1):144–150. DOI: 10.1002/clc.22842
- Voros S, Maurovich-Horvat P, Marvasty IB, Bansal AT, Barnes MR, Vazquez G, et al. Precision phenotyping, panomics, and system-level bioinformatics to delineate complex biologies of atherosclerosis: Rationale and design of the “Genetic Loci and the Burden of Atherosclerotic Lesions” study. J Cardiovasc Comput Tomogr. 2014;8(6):442–451. DOI: 10.1016/j.jcct.2014.08.006
- Hasin Y, Seldin M, Lusis A. Multi-omics approaches to disease. Genome Biol. 2017;18(1):
83 . DOI: 10.1186/s13059-017-1215-1 - Sniderman AD, Thanassoulis G, Glavinovic T, Navar AM, Pencina M, Catapano A, et al. Apolipoprotein B particles and cardiovascular disease: A narrative review. JAMA Cardiol. 2019;4(12):1287–1295. DOI: 10.1001/jamacardio.2019.3780
- Šuran D, Blažun Vošner H, Završnik J, Kokol P, Sinkovič A, Kanič V, et al. Lipoprotein(a) in cardiovascular diseases: Insight from a bibliometric study. Front Public Health. 2022;10:
923797 . DOI: 10.3389/fpubh.2022.923797 - Boffa MB, Koschinsky ML. Lipoprotein (a): Truly a direct prothrombotic factor in cardiovascular disease? J Lipid Res. 2016;57(5):745–757. DOI: 10.1194/jlr.R060582
- Kronenberg F, Utermann G. Lipoprotein(a): Resurrected by genetics. J Intern Med. 2013;273(1):6–30. DOI: 10.1111/j.1365-2796.2012.02592.x
- Voros S, Brown BO, Watson DS, Boatwright W, Dayspring T, Barnes MR. Elevated levels of Lp(a) are associated with circulating levels of PCSK9 and coronary atherosclerosis as detected by cardiac computed tomography angiography. National Lipid Association (NLA) Scientific Sessions;
May 30–June 2, 2024 ; Las Vegas, NV, USA. - Chan DC, Watts GF, Coll B, Wasserman SM, Marcovina SM, Barrett PHR. Lipoprotein(a) particle production as a determinant of plasma lipoprotein(a) concentration across varying apolipoprotein(a) isoform sizes and background cholesterol-lowering therapy. J Am Heart Assoc. 2019;8(7):
e011781 . DOI: 10.1161/JAHA.118.011781 - Afanasieva OI, Tyurina AV, Ezhov MV, Razova OA, Klesareva EA, Pokrovsky SN. Lipoprotein(a) and low-molecular-weight Apo(a) phenotype as determinants of new cardiovascular events in patients with premature coronary heart disease. Diseases. 2023;11(4):
145 . DOI: 10.3390/diseases11040145 - Langsted A, Kamstrup PR, Nordestgaard BG. High lipoprotein(a) and high risk of mortality. Eur Heart J. 2019;40(33):2760–2770. DOI: 10.1093/eurheartj/ehy902
- Kaiser Y, Daghem M, Tzolos E, Meah MN, Doris MK, Moss AJ, et al. Association of lipoprotein(a) with atherosclerotic plaque progression. J Am Coll Cardiol. 2022;79(3):223–233. DOI: 10.1016/j.jacc.2021.10.044
- van Dijk RA, Kolodgie F, Ravandi A, Leibundgut G, Hu PP, Prasad A, et al. Differential expression of oxidation-specific epitopes and apolipoprotein(a) in progressing and ruptured human coronary and carotid atherosclerotic lesions. J Lipid Res. 2012;53(12):2773–2790. DOI: 10.1194/jlr.P030890
- Dweck MR, Maurovich-Horvat P, Leiner T, Cosyns B, Fayad ZA, Gijsen FJH, et al. Contemporary rationale for non-invasive imaging of adverse coronary plaque features to identify the vulnerable patient: A Position Paper from the European Society of Cardiology Working Group on Atherosclerosis and Vascular Biology and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2020;21(11):1177–1183. DOI: 10.1093/ehjci/jeaa201
- Kolossváry M, Szilveszter B, Édes IF, Nardai S, Voros V, Hartyánszky I, et al. Comparison of quantity of coronary atherosclerotic plaques detected by computed tomography versus angiography. Am J Cardiol. 2016;117(12):1863–1867. DOI: 10.1016/j.amjcard.2016.03.031
- Blankstein R, Shiyovich A. Can plaque imaging improve risk assessment among individuals with elevated Lp(a)? J Am Coll Cardiol. 2024;83(18):1756–1759. DOI: 10.1016/j.jacc.2024.03.386
- Niccoli G, Cin D, Scalone G, Panebianco M, Abbolito S, Cosentino N, et al. Lipoprotein (a) is related to coronary atherosclerotic burden and a vulnerable plaque phenotype in angiographically obstructive coronary artery disease. Atherosclerosis. 2016;246:214–220. DOI: 10.1016/j.atherosclerosis.2016.01.020
- Nurmohamed NS, Gaillard EL, Malkasian S, de Groot RJ, Ibrahim S, Bom MJ, et al. Lipoprotein(a) and long-term plaque progression, low-density plaque, and pericoronary inflammation. JAMA Cardiol. 2024;9(9):826–834. DOI: 10.1001/jamacardio.2024.1874
- Yeang C, Cotter B, Tsimikas S. Experimental animal models evaluating the causal role of lipoprotein(a) in atherosclerosis and aortic stenosis. Cardiovasc Drugs Ther. 2016;30(1):75–85. DOI: 10.1007/s10557-015-6634-1
- Assini JM, Clark JR, Youssef A, Xing C, Doerfler AM, Park SH, et al. High levels of lipoprotein(a) in transgenic mice exacerbate atherosclerosis and promote vulnerable plaque features in a sex-specific manner. Atherosclerosis. 2023;384:
117150 . DOI: 10.1016/j.atherosclerosis.2023.05.019 - Joshi A, Rienks M, Theofilatos K, Mayr M. Systems biology in cardiovascular disease: A multiomics approach. Nat Rev Cardiol. 2021;18(5):313–330. DOI: 10.1038/s41569-020-00477-1
- Voros S, Bansal AT, Barnes MR, Narula J, Maurovich-Horvat P, Vazquez G, et al. Bayesian network analysis of panomic biological big data identifies the importance of triglyceride-rich LDL in atherosclerosis development. Front Cardiovasc Med. 2022;9:
960419 . DOI: 10.3389/fcvm.2022.960419 - Leon-Mimila P, Wang J, Huertas-Vazquez A. Relevance of multi-omics studies in cardiovascular diseases. Front Cardiovasc Med. 2019;6:
91 . DOI: 10.3389/fcvm.2019.00091 - Chen G, Yao C, Hwang SJ, Liu C, Song C, Huan T, et al. Integrated proteomic analysis of cardiovascular disease reveals novel protein quantitative trait loci. Circulation. 2016;134(Suppl. 1):Abstract
18806 .https://www.ahajournals.org/doi/10.1161/circ.134.suppl_1.18806 - Vakili D, Radenkovic D, Chawla S, Bhatt DL. Panomics: New databases for advancing cardiology. Front Cardiovasc Med. 2021;8:
587768 . DOI: 10.3389/fcvm.2021.587768 - Khomtchouk BB, Vand KA, Koehler WC, Tran DT, Middlebrook K, Sudhakaran S, et al. HeartBioPortal. Circ Genom Precis Med. 2019;12(4):
e002426 . DOI: 10.1161/CIRCGEN.118.002426 - G3 Therapeutics. Little (a), big risk: G3 Therapeutics sets out to unravel Lp(a)-driven cardiovascular disease (lipoprotein(a)-driven cardiovascular disease). [Internet]; 2024 Jan 04 [cited 2026 Jan 29]. Available from:
https://www.prnewswire.com/news-releases/little-a-big-risk-g3-therapeutics-sets-out-to-unravel-lpa-driven-cardiovascular-disease-lipoproteina-driven-cardiovascular-disease-302025736 - Hou ZH, Lu B, Gao Y, Jiang SL, Wang Y, Li W, et al. Prognostic value of coronary CT angiography and calcium score for major adverse cardiac events in outpatients. JACC Cardiovasc Imaging. 2012;5(10):990–999. DOI: 10.1016/j.jcmg.2012.06.006
- Linton MF, Yancey PG, Davies SS, Jerome WG, Linton EF, Song WL, et al.
The role of lipids and lipoproteins in atherosclerosis . In: Adler RA, Ahmed SF, Anawalt B, Blackman MR, Chrousos G, Corpas E, et al., editors. Endotext. South Dartmouth, MA: MDText.com, Inc.; 2000. - Durham AL, Speer MY, Scatena M, Giachelli CM, Shanahan CM. Role of smooth muscle cells in vascular calcification: Implications in atherosclerosis and arterial stiffness. Cardiovasc Res. 2018;114(4):590–600. DOI: 10.1093/cvr/cvy010
- Maurovich-Horvat P, Schlett CL, Alkadhi H, Nakano M, Otsuka F, Stolzmann P, et al. The napkin-ring sign indicates advanced atherosclerotic lesions in coronary CT angiography. JACC Cardiovasc Imaging. 2012;5(12):1243–1252. DOI: 10.1016/j.jcmg.2012.03.019
- Brown B, Watson D, Boatwright W, Dayspring T, Barnes M, Voros S. Elevated levels of Lp(a) are associated with circulating levels of PCSK9 and coronary atherosclerosis as detected by cardiac computed tomography angiography. Journal of Clinical Lipidology. 2024;18(4):e577–e578. DOI: 10.1016/j.jacl.2024.04.117
- Kronenberg F, Mora S, Stroes ESG, Ference BA, Arsenault BJ, Berglund L, et al. Frequent questions and responses on the 2022 lipoprotein(a) consensus statement of the European Atherosclerosis Society. Atherosclerosis. 2023;374:107–120. DOI: 10.1016/j.atherosclerosis.2023.04.012
- Marcovina SM, Albers JJ, Gabel B, Koschinsky ML, Gaur VP. Effect of the number of apolipoprotein(a) kringle 4 domains on immunochemical measurements of lipoprotein(a). Clin Chem. 1995;41(2):246–255. DOI: 10.1093/clinchem/41.2.246
- Erqou S, Thompson A, Di Angelantonio E, Saleheen D, Kaptoge S, Marcovina S, et al. Apolipoprotein(a): Isoforms and the risk of vascular disease: Systematic review of 40 studies involving 58,000 participants. J Am Coll Cardiol. 2010;55(19):2160–2167. DOI: 10.1016/j.jacc.2009.10.080
- Saleheen D, Haycock PC, Zhao W, Rasheed A, Taleb A, Imran A, et al. Apolipoprotein(a) isoform size, lipoprotein(a) concentration, and coronary artery disease: A mendelian randomisation analysis. Lancet Diabetes Endocrinol. 2017;5(7):524–533. DOI: 10.1016/s2213-8587(17)30088-8