Lipoprotein(a): Assessing the Current Knowledge and Gaps in Screening and Treatment—A Narrative Review

Atherosclerotic cardiovascular disease (ASCVD) has long been screened using the traditional lipid profile, mainly focusing on LDL cholesterol. However, despite growing evidence supporting lipoprotein(a) [Lp(a)] as an independent risk factor involved in atherosclerosis, its clinical use remains limit...

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Main Authors: Octavian Amaritei, Oana Laura Mierlan, Cristian Gutu, Gabriela Gurau
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Journal of Cardiovascular Development and Disease
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Online Access:https://www.mdpi.com/2308-3425/12/5/169
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author Octavian Amaritei
Oana Laura Mierlan
Cristian Gutu
Gabriela Gurau
author_facet Octavian Amaritei
Oana Laura Mierlan
Cristian Gutu
Gabriela Gurau
author_sort Octavian Amaritei
collection DOAJ
description Atherosclerotic cardiovascular disease (ASCVD) has long been screened using the traditional lipid profile, mainly focusing on LDL cholesterol. However, despite growing evidence supporting lipoprotein(a) [Lp(a)] as an independent risk factor involved in atherosclerosis, its clinical use remains limited. This review examines the reasons behind the limited use of Lp(a) screening in clinical practice, assessing its role in cardiovascular risk, comparing it to traditional lipid markers and evaluating current assessment methods. It also explores existing and emerging treatments, including gene-silencing therapies, for managing elevated Lp(a) levels. One in four clinicians does not routinely check Lp(a) levels, which proves a lack of awareness amongst them. The reasons for that are implied to be that the cost is too high and that available treatments are scarce. The traditional lipid profile, including LDL, high-density lipoprotein (HDL) and triglycerides, continues to be the gold standard for CV risk assessment. One limitation of using Lp(a) in clinical practice is the significant variability in apo(a) sizes, which results from the presence of multiple isoforms determined by the number of kringle domains. This structural diversity poses challenges in standardizing measurement methods, affecting the accuracy and comparability of results. While statins have a minimal impact on Lp(a), PCSK9-i lowers its levels by 20–25%, although this class is not prescribed primarily for this reason. Lastly, gene-silencing therapies, which achieve the greatest reduction in Lp(a) levels, are still in phase III trials, and there is still a need to examine whether this reduction translates into CV benefits. These limitations should not discourage further research, because ASCVD’s complexity requires a more tailored approach. Current lipid-lowering therapy still fails in a minority of cases, as evidenced by new-onset cardiovascular events in patients with well-controlled LDL levels. There is a need for future interventional studies to assess whether a reduction in Lp(a) by PCSK9-i really translates into CV benefits, independent of LDL.
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spelling doaj-art-e31f87643fa44e59ab08603f16342d312025-08-20T03:47:57ZengMDPI AGJournal of Cardiovascular Development and Disease2308-34252025-04-0112516910.3390/jcdd12050169Lipoprotein(a): Assessing the Current Knowledge and Gaps in Screening and Treatment—A Narrative ReviewOctavian Amaritei0Oana Laura Mierlan1Cristian Gutu2Gabriela Gurau3Faculty of Medicine and Pharmacy, “Dunărea de Jos” University of Galați, 800008 Galați, RomaniaFaculty of Medicine and Pharmacy, “Dunărea de Jos” University of Galați, 800008 Galați, RomaniaFaculty of Medicine and Pharmacy, “Dunărea de Jos” University of Galați, 800008 Galați, RomaniaFaculty of Medicine and Pharmacy, “Dunărea de Jos” University of Galați, 800008 Galați, RomaniaAtherosclerotic cardiovascular disease (ASCVD) has long been screened using the traditional lipid profile, mainly focusing on LDL cholesterol. However, despite growing evidence supporting lipoprotein(a) [Lp(a)] as an independent risk factor involved in atherosclerosis, its clinical use remains limited. This review examines the reasons behind the limited use of Lp(a) screening in clinical practice, assessing its role in cardiovascular risk, comparing it to traditional lipid markers and evaluating current assessment methods. It also explores existing and emerging treatments, including gene-silencing therapies, for managing elevated Lp(a) levels. One in four clinicians does not routinely check Lp(a) levels, which proves a lack of awareness amongst them. The reasons for that are implied to be that the cost is too high and that available treatments are scarce. The traditional lipid profile, including LDL, high-density lipoprotein (HDL) and triglycerides, continues to be the gold standard for CV risk assessment. One limitation of using Lp(a) in clinical practice is the significant variability in apo(a) sizes, which results from the presence of multiple isoforms determined by the number of kringle domains. This structural diversity poses challenges in standardizing measurement methods, affecting the accuracy and comparability of results. While statins have a minimal impact on Lp(a), PCSK9-i lowers its levels by 20–25%, although this class is not prescribed primarily for this reason. Lastly, gene-silencing therapies, which achieve the greatest reduction in Lp(a) levels, are still in phase III trials, and there is still a need to examine whether this reduction translates into CV benefits. These limitations should not discourage further research, because ASCVD’s complexity requires a more tailored approach. Current lipid-lowering therapy still fails in a minority of cases, as evidenced by new-onset cardiovascular events in patients with well-controlled LDL levels. There is a need for future interventional studies to assess whether a reduction in Lp(a) by PCSK9-i really translates into CV benefits, independent of LDL.https://www.mdpi.com/2308-3425/12/5/169lipoprotein(a)LDL cholesterolcardiovascular diseaseatherosclerosisPCSK9-iASO
spellingShingle Octavian Amaritei
Oana Laura Mierlan
Cristian Gutu
Gabriela Gurau
Lipoprotein(a): Assessing the Current Knowledge and Gaps in Screening and Treatment—A Narrative Review
Journal of Cardiovascular Development and Disease
lipoprotein(a)
LDL cholesterol
cardiovascular disease
atherosclerosis
PCSK9-i
ASO
title Lipoprotein(a): Assessing the Current Knowledge and Gaps in Screening and Treatment—A Narrative Review
title_full Lipoprotein(a): Assessing the Current Knowledge and Gaps in Screening and Treatment—A Narrative Review
title_fullStr Lipoprotein(a): Assessing the Current Knowledge and Gaps in Screening and Treatment—A Narrative Review
title_full_unstemmed Lipoprotein(a): Assessing the Current Knowledge and Gaps in Screening and Treatment—A Narrative Review
title_short Lipoprotein(a): Assessing the Current Knowledge and Gaps in Screening and Treatment—A Narrative Review
title_sort lipoprotein a assessing the current knowledge and gaps in screening and treatment a narrative review
topic lipoprotein(a)
LDL cholesterol
cardiovascular disease
atherosclerosis
PCSK9-i
ASO
url https://www.mdpi.com/2308-3425/12/5/169
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AT oanalauramierlan lipoproteinaassessingthecurrentknowledgeandgapsinscreeningandtreatmentanarrativereview
AT cristiangutu lipoproteinaassessingthecurrentknowledgeandgapsinscreeningandtreatmentanarrativereview
AT gabrielagurau lipoproteinaassessingthecurrentknowledgeandgapsinscreeningandtreatmentanarrativereview