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Serum PCSK9 is modified by interleukin-6 receptor antagonism in patients with hypercholesterolaemia following non-ST-elevation myocardial infarction.

ABSTRACT: Objective:It is unclear if activation of inflammatory pathways regulates proprotein convertase subtilisin-kexin type 9 (PCSK9) levels. Approach:We evaluated (1) the temporal course of serum PCSK9 during hospitalisation following acute coronary syndrome and associations with markers of inflammation (leucocyte counts, interleukin (IL)-6, C-reactive protein) and lipid levels and (2) the effect of inhibition of IL-6 signalling with the IL-6 receptor antibody tocilizumab on PCSK9 levels in a randomised, double-blind, placebo-controlled trial release in patients with non-ST-elevation myocardial infarction. Results:Serum PCSK9 increased during the acute phase and this response was modestly associated with neutrophil counts (r=0.24, p=0.009) and presence of hypercholesterolaemia (r=0.019, p=0.045), but was not modified by tocilizumab. However, a modifying effect of tocilizumab on PCSK9 levels was observed in patients with hypercholesterolaemia (p=0.024, repeated measures analysis of variance) and this effect was strongly correlated with the decrease in neutrophils (r=0.66, p=0.004). Conclusions:Our study suggests that patients with a more atherogenic profile may benefit from anti-IL-6 therapy with regard to PCSK9. Trial registration number:NCT01491074.

SUBMITTER: Ueland T

PROVIDER: S-EPMC6150185 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Serum PCSK9 is modified by interleukin-6 receptor antagonism in patients with hypercholesterolaemia following non-ST-elevation myocardial infarction.

Ueland Thor T Kleveland Ola O Michelsen Annika E AE Wiseth Rune R Damås Jan Kristian JK Aukrust Pål P Gullestad Lars L Halvorsen Bente B Yndestad Arne A

Open heart 20180918 2

<h4>Objective</h4>It is unclear if activation of inflammatory pathways regulates proprotein convertase subtilisin-kexin type 9 (PCSK9) levels.<h4>Approach</h4>We evaluated (1) the temporal course of serum PCSK9 during hospitalisation following acute coronary syndrome and associations with markers of inflammation (leucocyte counts, interleukin (IL)-6, C-reactive protein) and lipid levels and (2) the effect of inhibition of IL-6 signalling with the IL-6 receptor antibody tocilizumab on PCSK9 level ...[more]

PMID: 30258647

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Project description:ImportanceMyocardial tissue injury due to acute ST-elevation myocardial infarction (STEMI) initiates an inflammatory response that leads to a release of systemic inflammatory biomarkers, including C-reactive protein (CRP) and white blood cells, consequently reducing the usefulness of these routine biomarkers for identifying concomitant infections. The clinical role of procalcitonin (PCT), a promising marker of bacterial infection, to detect concomitant infection in acute STEMI is unknown, mainly because it is unclear whether myocardial injury per se induces systemic PCT release.ObjectiveTo investigate the release of serum PCT in the acute setting of STEMI (24 and 48 hours after primary percutaneous coronary intervention) and to elucidate any associations with myocardial injury markers through a comprehensive assessment by cardiac magnetic resonance (CMR) imaging.Design, setting, and participantsThis prospective cohort study conducted between 2016 and 2018 included 141 consecutive patients with STEMI treated with primary percutaneous coronary intervention. Concentrations of PCT, high-sensitivity CRP (hs-CRP), and high-sensitivity cardiac troponin T (hs-cTnT) and white blood cell counts were measured serially 24 and 48 hours after infarct.ExposuresAcute STEMI and primary percutaneous coronary intervention.Main outcomes and measuresThe association of PCT and typical inflammatory marker levels with CMR-determined myocardial damage was assessed. Infarct size, extent of microvascular obstruction, and occurrence of intramyocardial hemorrhage as determined by CMR within the first week following STEMI were also evaluated.ResultsIn total, 141 patients with STEMI (117 men [83%]) having a median age of 56 years (interquartile range, 50-66 years) were included. The median PCT concentration was 0.07 μg/L (interquartile range, <0.06-0.11 μg/L) 24 hours after intervention and 0.07 μg/L (interquartile range, <0.06-0.09 μg/L) 48 hours after intervention. Whereas hs-CRP and hs-cTnT levels and white blood cell counts were significantly correlated with CMR markers of myocardial damage at both 24 and 48 hours after intervention, the PCT level showed no significant correlation with infarct size (at 24 hours: r = 0.07; P = .40; at 48 hours: r = 0.13; P = .12) or with microvascular obstruction (at 24 hours: r = -0.03; P = .75; at 48 hours: r = 0.09; P = .30). Furthermore, PCT levels at 24 hours (odds ratio, 1.25; 95% CI, 0.63-2.48; P = .52) and 48 hours (odds ratio, 1.56; 95% CI, 0.72-3.41; P = .26) were not significantly associated with the presence of intramyocardial hemorrhage.Conclusions and relevanceIn the acute phase after percutaneous coronary intervention for STEMI, circulating PCT levels remained unassociated with the extent of myocardial and microvascular tissue damage as visualized by CMR imaging.

Dataset Information

Serum PCSK9 is modified by interleukin-6 receptor antagonism in patients with hypercholesterolaemia following non-ST-elevation myocardial infarction.

Publications

Serum PCSK9 is modified by interleukin-6 receptor antagonism in patients with hypercholesterolaemia following non-ST-elevation myocardial infarction.

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