Lipoprotein(a): An update on its role in human health and disease

Koutsogianni, Amalia-Despoina; Liberopoulos, Evangelos; Tselepis, Alexandros D.

doi:10.53590/japt.02.1028

Cited by 4 publications

(16 citation statements)

References 80 publications

(112 reference statements)

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“…Currently, there are no medications specifically approved for Lp(a)-lowering [ 23 , 24 , 25 ]. However, clinical trials in the advanced stages of development with novel agents targeting Lp(a) are ongoing.…”

Section: Introductionmentioning

confidence: 99%

“…However, clinical trials in the advanced stages of development with novel agents targeting Lp(a) are ongoing. Interestingly, some therapeutic agents of various drug classes appear to affect Lp(a) concentrations [ 23 , 24 , 25 ]. In this narrative review, we discuss the effects of current and future lipid-modifying and non-lipid-modifying medical interventions on Lp(a) levels and their potent clinical implications.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Lipid-Modifying and Other Drugs on Lipoprotein(a) Levels—Potent Clinical Implications

et al. 2023

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The past few years have shown an ongoing interest in lipoprotein(a) (Lp(a)), a lipid molecule that has been proven to have atherogenic, thrombogenic, and inflammatory properties. Several lines of evidence, indeed, have demonstrated an increased risk of cardiovascular disease as well as calcific aortic valve stenosis in patients with elevated Lp(a) levels. Statins, the mainstay of lipid-lowering therapy, slightly increase Lp(a) levels, while most other lipid-modifying agents do not significantly alter Lp(a) concentrations, except for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. The latter have been shown to reduce Lp(a) levels; however, the clinical significance of this effect has not been clearly elucidated. Of note, the pharmaceutical lowering of Lp(a) may be achieved with novel treatments specifically designed for this purpose (i.e., antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs)). Large clinical trials with cardiovascular outcomes with these agents are ongoing, and their results are eagerly awaited. Furthermore, several non-lipid-modifying drugs of various classes may influence Lp(a) concentrations. We have searched MEDLINE, EMBASE, and CENTRAL databases up to 28 January 2023 and summarized the effects of established and emerging lipid-modifying drugs and other medications on Lp(a) levels. We also discuss the potent clinical implications of these alterations.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of Lipid-Modifying and Other Drugs on Lipoprotein(a) Levels—Potent Clinical Implications

et al. 2023

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“…Lipoprotein(a) (Lp(a)) consists of a low-density lipoprotein (LDL)-like particle to which a large, highly glycosylated apolipoprotein(a) (apo(a)) is covalently bound to the apoB-100 moiety of LDL via a single disulfide bond [ 1 – 3 ] (Fig. 1 ).…”

Section: Introductionmentioning

confidence: 99%

“…Apo(a) is highly homologous to the plasma protease zymogen, plasminogen, which contains five tri-loop structures stabilized by three disulfide bonds, named kringles (K), and a protease domain, thus it can be activated to plasmin. Apo(a) contains only KIV and KV and has a protease-like domain that is catalytically inactive, despite having an intact Ser-His-Asp catalytic triad [ 1 – 3 ]. Importantly, apo(a) contains 10 subtypes of KIV (KIV-1 to KIV-10); the KIV-2 subtype being present in variable numbers (5 to 50) of identically-repeated copies.…”

Section: Introductionmentioning

confidence: 99%

“…Importantly, apo(a) contains 10 subtypes of KIV (KIV-1 to KIV-10); the KIV-2 subtype being present in variable numbers (5 to 50) of identically-repeated copies. Thus, apo(a) is highly polymorphic in length due to the number variation of the KIV-2 copies [ 1 , 2 ]. Apo(a) is encoded by the LPA gene, which contains a 5.6-kb segment existing in multiple repeats (KIV-2 repeat polymorphism) that is responsible for the apo(a) isoform variation [ 1 – 3 , 5 •].…”

Section: Introductionmentioning

confidence: 99%

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Treatment of Lp(a): Is It the Future or Are We Ready Today?

Tselepis

2023

Curr Atheroscler Rep

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Purpose of Review The goal of this review is to present the pharmacodynamic effectiveness as well as the clinical efficacy and safety of investigational antisense oligonucleotides (ASOs) and small interference RNAs (siRNAs) drugs that specifically target lipoprotein(a) (Lp(a)). The review will discuss whether the existing lipid-lowering therapies are adequate to treat high Lp(a) levels or whether it is necessary to use the emerging new therapeutic approaches which are based on the current RNA technologies. Recent Findings Lipoprotein(a) (Lp(a)) is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD), independent of other conventional risk factors. High Lp(a) levels are also independently associated with an increased risk of aortic stenosis progression rate. Plasma Lp(a) levels are primarily genetically determined by variation in the LPA gene coding for apo(a). All secondary prevention trials have demonstrated that the existing hypolipidemic therapies are not adequate to reduce Lp(a) levels to such an extent that could lead to a substantial reduction of ASCVD risk. This has led to the development of new drugs that target the mRNA transcript of LPA and efficiently inhibit Lp(a) synthesis leading to potent Lp(a) reduction. These new drugs are the ASO pelacarsen and the siRNAs olpasiran and SLN360. Recent pharmacodynamic studies showed that all these drugs potently reduce Lp(a) up to 98%, in a dose-dependent manner. Ongoing clinical trials will determine the Lp(a)-lowering efficacy, tolerability, and safety of these drugs as well as their potential effectiveness in reducing the ASCVD risk attributed to high plasma Lp(a) levels. Summary We are not ready today to significantly reduce plasma Lp(a). Emerging therapies potently decrease Lp(a) and ongoing clinical trials will determine their effectiveness in reducing ASCVD risk in subjects with high Lp(a) levels.

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Familial Hypercholesterolemia and Lipoprotein(a): A Gordian Knot in Cardiovascular Prevention

et al. 2022

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Familial hypercholesterolemia (FH) is the most frequent genetic disorder resulting in increased low-density lipoprotein cholesterol (LDL-C) levels from childhood, leading to premature atherosclerotic cardiovascular disease (ASCVD) if left untreated. FH diagnosis is based on clinical criteria and/or genetic testing and its prevalence is estimated as being up to 1:300,000–400,000 for the homozygous and ~1:200–300 for the heterozygous form. Apart from its late diagnosis, FH is also undertreated, despite the available lipid-lowering therapies. In addition, elevated lipoprotein(a) (Lp(a)) (>50 mg/dL; 120 nmol/L), mostly genetically determined, has been identified as an important cardiovascular risk factor with prevalence rate of ~20% in the general population. Novel Lp(a)-lowering therapies have been recently developed and their cardiovascular efficacy is currently investigated. Although a considerable proportion of FH patients is also diagnosed with high Lp(a) levels, there is a debate whether these two entities are associated. Nevertheless, Lp(a), particularly among patients with FH, has been established as a significant cardiovascular risk factor. In this narrative review, we present up-to-date evidence on the pathophysiology, diagnosis, and treatment of both FH and elevated Lp(a) with a special focus on their association and joint effect on ASCVD risk.

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Lipoprotein(a): An update on its role in human health and disease

Cited by 4 publications

References 80 publications

Effects of Lipid-Modifying and Other Drugs on Lipoprotein(a) Levels—Potent Clinical Implications

Effects of Lipid-Modifying and Other Drugs on Lipoprotein(a) Levels—Potent Clinical Implications

Treatment of Lp(a): Is It the Future or Are We Ready Today?

Familial Hypercholesterolemia and Lipoprotein(a): A Gordian Knot in Cardiovascular Prevention

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