Author(s) |
Watts, Gerald F
Chan, Dick C
Pang, Jing
Ma, Louis
Ying, Qidi
Aggarwal, Shashi
Marcovina, Santica M
Barrett, P Hugh R
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Publication Date |
2020-06-01
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Abstract |
<p><i>Background:</i> Lipoprotein(a) (Lp(a)) is a low-density lipoprotein (LDL) particle containing apolipoprotein(a) (apo(a)) covalently linked to apolipoprotein B-100 (apoB). Statin-treated patients with elevated Lp(a) have an increased risk of atherosclerotic cardiovascular disease (ASCVD). Recent trials show that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition decreases Lp(a) and cardiovascular events, particularly in high risk patients with elevated Lp(a). We investigated the kinetic mechanism whereby alirocumab, a PCSK9 inhibitor, lowers Lp(a) in statin-treated patients with high Lp(a) and ASCVD.</p><p> <i>Methods:</i> The effects of 12-week alirocumab treatment (150 mg every 2 weeks) on apo(a) kinetics were studied in 21 patients with elevated Lp(a) concentration (>0.5 g/L). Apo(a) fractional catabolic rate (FCR) and production rate (PR) were determined using intravenous D3-leucine administration, mass spectrometry and compartmental modelling. All patients were on long-term statin treatment.</p><p> <i>Results:</i> Alirocumab significantly decreased plasma concentrations of total cholesterol (-39%), LDL-cholesterol (-67%), apoB (-56%), apo(a) (-25%) and Lp(a) (-22%) (P< 0.001 for all). Alirocumab also significantly lowered plasma apo(a) pool size (-26%, P <0.001) and increased the FCR of apo(a) (+28%, P< 0.001), but did not alter apo(a) PR, which remained significantly higher relative to a reference group of patients on statins with normal Lp(a) (P< 0.001).</p><p> <i>Conclusions:</i> In statin-treated patients, alirocumab lowers elevated plasma Lp(a) concentrations by accelerating the catabolism of Lp(a) particles. This may be consequent on marked upregulation of hepatic receptors (principally for LDL) and/or reduced competition between Lp(a) and LDL particles for these receptors; the mechanism could contribute to the benefit of PCSK9 inhibition with alirocumab on cardiovascular outcomes.</p>
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Citation |
Metabolism, v.107, p. 1-8
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ISSN |
1532-8600
0026-0495
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Link | |
Publisher |
Elsevier Inc
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Title |
PCSK9 Inhibition with alirocumab increases the catabolism of lipoprotein(a) particles in statin-treated patients with elevated lipoprotein(a)
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Type of document |
Journal Article
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Entity Type |
Publication
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