Plasma or serum concentrations of lipoprotein(a) - Lp(a) - are an established marker
of risk for atherothrombotic cardiovascular disease (CVD) and for degenerative aortic
valve stenosis (
[1]
). Mechanistic experiments, prospective observations, and genetic studies strongly
support a causal role of Lp(a) for CVD development (
- Wohlfahrt P.
- Jenča D.
- Melenovský V.
- Franeková J.
- Jabor A.
- Šramko M.
- Staněk V.
- Želízko M.
- Poledne R.
- Piťha J.
- Adámková V.
- Kautzner J.
Very low lipoprotein(a) and increased mortality risk after myocardial infarction.
Eur J Intern Med. 2021; S0953-6205 (00135-7)https://doi.org/10.1016/j.ejim.2021.04.012
1
,
- Wohlfahrt P.
- Jenča D.
- Melenovský V.
- Franeková J.
- Jabor A.
- Šramko M.
- Staněk V.
- Želízko M.
- Poledne R.
- Piťha J.
- Adámková V.
- Kautzner J.
Very low lipoprotein(a) and increased mortality risk after myocardial infarction.
Eur J Intern Med. 2021; S0953-6205 (00135-7)https://doi.org/10.1016/j.ejim.2021.04.012
2
,
3
). Apolipoprotein(a) is synthesised mostly in the liver and is exclusively bound to
low-density lipoprotein (LDL) to form Lp(a). The latter contributes to arterial lipid
deposits (
[4]
) and can inhibit endogenous fibrinolysis by competing with plasminogen for fibrin
binding (
[3]
). Significant reductions of circulating Lp(a) by monoclonal antibodies against interleukin(IL)−6
(ziltivekimab) (
[5]
) and IL-1β (canakinumab) (
- Ridker P.M.
- Devalaraja M.
- Baeres F.M.M.
- Engelmann M.D.M.
- Hovingh G.K.
- Ivkovic M.
- Lo L.
- Kling D.
- Pergola P.
- Raj D.
- Libby P.
- Davidson M.
- Investigators RESCUE
IL-6 inhibition with ziltivekimab in patients at high atherosclerotic risk (RESCUE):
a double-blind, randomised, placebo-controlled, phase 2 trial.
Lancet. 2021; 397: 2060-2069
[6]
) suggest involvement of Lp(a) in the nod-like receptor protein-3 inflammasome cascade
that generates IL-6, IL-1β and C-reactive protein. Circulating levels of Lp(a) are
considered relatively stable and largely genetically determined; laboratory measurements
are evolving toward a global standardization (
[2]
); at least one lifetime measure is recommended to assess CVD risk which is considered
significant for Lp(a) values ≥125 nM (
[1]
). Oral niacin and subcutaneous proprotein convertase subtilisin/kexin type 9 inhibitors
induce moderate Lp(a) reduction, with concomitant effects on LDL-cholesterol concentrations
(
- Wohlfahrt P.
- Jenča D.
- Melenovský V.
- Franeková J.
- Jabor A.
- Šramko M.
- Staněk V.
- Želízko M.
- Poledne R.
- Piťha J.
- Adámková V.
- Kautzner J.
Very low lipoprotein(a) and increased mortality risk after myocardial infarction.
Eur J Intern Med. 2021; S0953-6205 (00135-7)https://doi.org/10.1016/j.ejim.2021.04.012
[2]
); more intense and specific pharmacological interventions to lower Lp(a) include
inhibition of apolipoprotein(a) synthesis by the hepatocyte-directed antisense oligonucleotide
pelacarsen and by the short interfering RNAs olpasiran and SLN360 (
[2]
,
[3]
). Lp(a)HORIZON (NCT04023552) is the first ongoing large randomized CVD outcome trial
comparing subcutaneous pelacarsen (TQJ230) 80 mg monthly versus placebo; the study
plans to enrol 7680 patients with a history of myocardial infarction (MI) or ischemic
stroke or significant peripheral artery disease and with baseline Lp(a) >140 nM in
order to accrue 993 events; completion date is estimated in June 2024 (
[2]
).Keywords
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Article info
Publication history
Published online: August 02, 2021
Accepted:
July 15,
2021
Received:
July 6,
2021
Identification
Copyright
© 2021 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
