Purpose of Review: A considerable body of data from genetic and epidemiological studies strongly support a causal relationship between high lipoprotein(a) [Lp(a)] levels, and the development of atherosclerosis and cardiovascular disease. This relationship is continuous, unrelated to Lp(a) threshold, and independent of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels. Unfortunately, the mechanism(s) through which Lp(a) promotes atherosclerosis are not clarified yet. Suggested hypotheses include: an increased Lp(a)-associated cholesterol entrapment in the arterial intima followed by inflammatory cell recruitment, abnormal upload of proinflammatory oxidized phospholipids, impaired fibrinolysis by inhibition of plasminogen activation, and enhanced coagulation, through inhibition of the tissue factor pathway inhibitor. This review is aimed at summarizing the available evidence on the topic. Recent Findings: There are two clinical forms, isolated hyperlipidemia(a) [HyperLp(a)] with acceptable LDL-C levels (< 70 mg/dL), and combined elevation of Lp(a) and LDL-C in plasma. To date, no drugs that selectively decrease Lp(a) are available. Some novel lipid-lowering drugs can lower Lp(a) levels, but to a limited extent, as their main effect is aimed at decreasing LDL-C levels. Significant Lp(a) lowering effects were obtained with nicotinic acid at high doses. However, adverse effects apart, nicotinic acid is no longer prescribed and available in Europe for clinical use, after European Agency of Medicines (EMA) ban. Summary: The only effective therapeutic option for now is Lipoprotein Apheresis (LA), albeit with some limitations. Lastly, it is to be acknowledged that the body of evidence confirming that reducing plasma isolated elevation of Lp(a) brings cardiovascular benefit is still insufficient. However, the growing bulk of clinical, genetic, mechanistic, and epidemiological available evidence strongly suggests that Lp(a) is likely to be the smoking gun.

Looking at Lp(a) and Related Cardiovascular Risk: from Scientific Evidence and Clinical Practice / Stulnig, T. M.; Morozzi, C.; Reindl-Schwaighofer, R.; Stefanutti, C.. - In: CURRENT ATHEROSCLEROSIS REPORTS. - ISSN 1523-3804. - 21:10(2019), p. 37. [10.1007/s11883-019-0803-9]

Looking at Lp(a) and Related Cardiovascular Risk: from Scientific Evidence and Clinical Practice

Morozzi C.;Stefanutti C.
2019

Abstract

Purpose of Review: A considerable body of data from genetic and epidemiological studies strongly support a causal relationship between high lipoprotein(a) [Lp(a)] levels, and the development of atherosclerosis and cardiovascular disease. This relationship is continuous, unrelated to Lp(a) threshold, and independent of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels. Unfortunately, the mechanism(s) through which Lp(a) promotes atherosclerosis are not clarified yet. Suggested hypotheses include: an increased Lp(a)-associated cholesterol entrapment in the arterial intima followed by inflammatory cell recruitment, abnormal upload of proinflammatory oxidized phospholipids, impaired fibrinolysis by inhibition of plasminogen activation, and enhanced coagulation, through inhibition of the tissue factor pathway inhibitor. This review is aimed at summarizing the available evidence on the topic. Recent Findings: There are two clinical forms, isolated hyperlipidemia(a) [HyperLp(a)] with acceptable LDL-C levels (< 70 mg/dL), and combined elevation of Lp(a) and LDL-C in plasma. To date, no drugs that selectively decrease Lp(a) are available. Some novel lipid-lowering drugs can lower Lp(a) levels, but to a limited extent, as their main effect is aimed at decreasing LDL-C levels. Significant Lp(a) lowering effects were obtained with nicotinic acid at high doses. However, adverse effects apart, nicotinic acid is no longer prescribed and available in Europe for clinical use, after European Agency of Medicines (EMA) ban. Summary: The only effective therapeutic option for now is Lipoprotein Apheresis (LA), albeit with some limitations. Lastly, it is to be acknowledged that the body of evidence confirming that reducing plasma isolated elevation of Lp(a) brings cardiovascular benefit is still insufficient. However, the growing bulk of clinical, genetic, mechanistic, and epidemiological available evidence strongly suggests that Lp(a) is likely to be the smoking gun.
2019
Apolipoprotein (a); Atherogenesis; Cardiovascular risk; Genetics; Lipoprotein (a); Thrombosis; Adult; Antibodies, Monoclonal, Humanized; Atherosclerosis; Blood Component Removal; Cholesterol, LDL; Humans; Hypolipidemic Agents; Lipoprotein(a); Middle Aged; Niacin; Oligonucleotides, Antisense; Risk Factors; Ubiquinone
01 Pubblicazione su rivista::01a Articolo in rivista
Looking at Lp(a) and Related Cardiovascular Risk: from Scientific Evidence and Clinical Practice / Stulnig, T. M.; Morozzi, C.; Reindl-Schwaighofer, R.; Stefanutti, C.. - In: CURRENT ATHEROSCLEROSIS REPORTS. - ISSN 1523-3804. - 21:10(2019), p. 37. [10.1007/s11883-019-0803-9]
File allegati a questo prodotto
File Dimensione Formato  
Stulnig_Looking_2019.pdf

solo gestori archivio

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 563.59 kB
Formato Adobe PDF
563.59 kB Adobe PDF   Contatta l'autore

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1493680
Citazioni
  • ???jsp.display-item.citation.pmc??? 9
  • Scopus 16
  • ???jsp.display-item.citation.isi??? 15
social impact