Metabolic effects of PCSK9 inhibition with Evolocumab in subjects with elevated Lp(a).

ABSTRACT: BACKGROUND:Epidemiological studies substantiated that subjects with elevated lipoprotein(a) [Lp(a)] have a markedly increased cardiovascular risk. Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) lowers both LDL cholesterol (LDL-C) as well as Lp(a), albeit modestly. Effects of PCSK9 inhibition on circulating metabolites such as lipoprotein subclasses, amino acids and fatty acids remain to be characterized. METHODS:We performed nuclear magnetic resonance (NMR) metabolomics on plasma samples derived from 30 individuals with elevated Lp(a) (>?150?mg/dL). The 30 participants were randomly assigned into two groups, placebo (N?=?14) and evolocumab (N?=?16). We assessed the effect of 16?weeks of evolocumab 420?mg Q4W treatment on circulating metabolites by running lognormal regression analyses, and compared this to placebo. Subsequently, we assessed the interrelationship between Lp(a) and 14 lipoprotein subclasses in response to treatment with evolocumab, by running multilevel multivariate regression analyses. RESULTS:On average, evolocumab treatment for 16?weeks resulted in a 17% (95% credible interval: 8 to 26%, P?

SUBMITTER: Zhang X 

PROVIDER: S-EPMC7216641 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature