Lipoprotein(a) as an Independent Risk Factor and Prognostic Marker of Obstructive Coronary Artery Atherosclerosis in Young Patients: A Literature
Abstract
Introduction. Lipoprotein(a) (Lp(a)) is a genetically determined, independent risk factor for premature coronary artery atherosclerosis, exhibiting atherogenic, prothrombotic, and pro-inflammatory properties.
Aim. To summarize current evidence on the pathophysiology, epidemiology, and clinical significance of Lp(a) in young patients with obstructive coronary artery atherosclerosis, and to review emerging therapeutic strategies for its reduction.
Results. Elevated Lp(a) levels (>125 nmol/L) are found in 20-30 % of the general population and up to 40% of young patients with premature coronary artery disease, including those without traditional risk factors. High Lp(a) levels correlate with disease severity (SYNTAX and Gensini scores) and increase the risk of reinfarction and restenosis after percutaneous interventions. Current therapeutic options are limited; the most promising are targeted genetic therapies (pelacarsen, olpasiran, SLN360), which can achieve 80-95 % reductions in Lp(a) levels.
Conclusions. Lp(a) measurement should be included in routine screening for high-risk groups. Incorporation of novel therapeutic strategies into clinical practice may significantly improve the prognosis of young patients with premature atherosclerosis.
References
- Roth GA, Mensah GA, Johnson CO, et al. Global Burden of Cardiovascular Diseases and Risk Factors, 1990–2019: Update From the GBD 2019 Study. J Am Coll Cardiol. 2020;76(25):2982–3021. https://doi.org/10.1016/j.jacc.2020.11.010
- World Health Organization. Cardiovascular diseases (CVDs) [Internet]. Geneva: WHO; 2023 [cited 2025 Aug 22]. Available from: https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)
- Virani SS, Alonso A, Aparicio HJ, et al. Heart Disease and Stroke Statistics — 2021 Update: A Report From the American Heart Association. Circulation. 2021;143(8):e254–e743. https://doi.org/10.1161/CIR.0000000000000950
- Bentzon JF, Otsuka F, Virmani R, Falk E. Mechanisms of plaque formation and rupture. Circ Res. 2019;114(12):1852–66. https://doi.org/10.1161/CIRCRESAHA.114.302721
- Shah NS, Molsberry R, Rana JS, Sidney S, Capewell S, O’Flaherty M, et al. Trends in premature heart disease mortality in the United States, 1999 to 2018. Circulation. 2021;144(2):120–38. https://doi.org/10.1161/CIRCULATIONAHA.120.050663
- Kronenberg F. Human genetics and the causal role of Lp(a). Cardiovasc Drugs Ther. 2016;30(1):87–100. https://doi.org/10.1007/s10557-016-6648-3
- Koschinsky ML, Boffa MB. Oxidized phospholipid modification of lipoprotein(a): Epidemiology, biochemistry and pathophysiology. Atherosclerosis. 2022;349:92–100. https://doi.org/10.1016/j.atherosclerosis.2022.04.001
- Mehta A, Virani SS, Ayers CR, et al. Elevated Lp(a) in young myocardial infarction. J Am Coll Cardiol. 2021;78(6):639–48. https://doi.org/10.1016/j.jacc.2021.05.040
- Mach F, Baigent C, Catapano AL, et al. 2021 ESC prevention guideline. Eur Heart J. 2021;42(34):3227–37. https://doi.org/10.1093/eurheartj/ehab484
- Arnett DK, Virani SS, Blumenthal RS, et al. 2023 AHA/ACC guideline. Circulation. 2023;148(6):e1–e110. https://doi.org/10.1161/CIR.0000000000001145
- 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(26):2518–28. https://doi.org/10.1056/NEJMoa0902604
- 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. https://doi.org/10.1016/j.atherosclerosis.2022.04.003
- Boffa MB, Koschinsky ML. Lipoprotein (a): truly a direct prothrombotic factor in cardiovascular disease? J Lipid Res. 2016;57(5):745–57. https://doi.org/10.1194/jlr.R060582
- Tsimikas S. A test in context: lipoprotein(a): diagnosis, prognosis, controversies, and emerging therapies. J Am Coll Cardiol. 2017;69(6):692–711. https://doi.org/10.1016/j.jacc.2016.11.042
- Gudbjartsson DF, Thorgeirsson G, Sulem P, et al. Lipoprotein(a) concentration and risks of cardiovascular disease and diabetes. J Am Coll Cardiol. 2019;74(24):2982–94. https://doi.org/10.1016/j.jacc.2019.10.019
- 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(3):250–2. https://doi.org/10.1161/CIRCULATIONAHA.124.069582
- Svintsitskyi IA, Mashkovska SI, Zaretska VV, Bulda VI. Diagnostic value of lipoprotein(a) and its indices as markers of obstructive coronary artery lesions in patients with stable ischemic heart disease. Cardiol Rheumatol. 2017;(11):2290. Available from: https://umj.com.ua/uk/publikatsia-116703-diagnostichna-tsinnist-lipoproteyinu-a-ta-jogo-indeksiv-yak-markeriv-obstruktivnogo-urazhennya-vintsevih-arterij-u-patsiyentiv-zi-stabilnoyu-ishemichnoyu-hvoroboyu-sertsya
- Novartis. Lp(a)HORIZON trial (NCT04023552). ClinicalTrials.gov [Internet]. 2023 [cited 2025 Aug 22]. Available from: https://clinicaltrials.gov/ct2/show/NCT04023552
- 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. https://doi.org/10.1016/j.atherosclerosis.2022.06.1023
- Gencer B, Kronenberg F, Stroes ES, Mach F. Lipoprotein(a): the revenant. Atherosclerosis. 2021;320:1–10. https://doi.org/10.1016/j.atherosclerosis.2021.01.016
- Mitchenko OI. Gender, clinical and instrumental parallels of lipoprotein(a) levels in patients with ischemic heart disease. Ukr J Cardiol. 2024;31(1):36–45. https://doi.org/10.31928/2664-4479-2024.2.5360
- Enkhmaa B, Anuurad E, Berglund L. Statins and Lp(a): The plot thickens. Atherosclerosis. 2019;289:173–5. https://doi.org/10.1016/j.atherosclerosis.2019.07.021
- Landray MJ, Hopewell JC, Parish S, et al. Niacin: updated evidence. Lancet Diabetes Endocrinol. 2022;10(6):415–25. https://doi.org/10.1016/S2213-8587(22)00103-7
- Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease (FOURIER trial). N Engl J Med. 2017;376(18):1713–22. https://doi.org/10.1056/NEJMoa1615664
- Schwartz GG, Steg PG, Szarek M, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome (ODYSSEY OUTCOMES trial). N Engl J Med. 2018;379(22):2097–107. https://doi.org/10.1056/NEJMoa1801174
- O’Donoghue ML, Fazio S, Giugliano RP, Stroes ESG, Kanevsky E, Gouni‑Berthold I, et al. Lipoprotein(a), PCSK9 inhibition, and cardiovascular risk insights from the FOURIER trial. Circulation. 2019;139(12):1483–92. https://doi.org/10.1161/CIRCULATIONAHA.118.037184
- Viney NJ, van Capelleveen JC, Geary RS, et al. Antisense oligonucleotides (pelacarsen) phase 2. Lancet. 2016;388(10057):2239–53. https://doi.org/10.1016/S0140-6736(16)31009-1
- O’Donoghue ML, Rosenson RS, Gencer B, López JAG, Lepor NE, Baum SJ, et al. Small interfering RNA to reduce lipoprotein(a) in cardiovascular disease. N Engl J Med. 2022;387(22):1855–64. https://doi.org/10.1056/NEJMoa2211023
- Nissen SE, Wolski K, Balog C, et al. Single ascending dose study of a short interfering RNA targeting lipoprotein(a) production in individuals with elevated plasma lipoprotein(a) levels. JAMA. 2022;327(17):1679–87. https://doi.org/10.1001/jama.2022.5050
- SCORE2 Working Group. SCORE2 risk prediction algorithms: New models to estimate 10-year risk of cardiovascular disease in Europe. Eur Heart J. 2021;42(25):2439–54. https://doi.org/10.1093/eurheartj/ehab309
- SCORE2 Working Group. SCORE2-OP risk prediction algorithms: Estimating cardiovascular risk in older persons in Europe. Eur Heart J. 2022;43(16):1612–23. https://doi.org/10.1093/eurheartj/ehab312
- Tsimikas S, Fazio S, Ferdinand K, 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):177–92. https://doi.org/10.1016/j.jacc.2017.11.014
- Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS dyslipidaemias guideline. Eur Heart J. 2020;41(1):111–88. https://doi.org/10.1093/eurheartj/ehz455