Long-Term Administration of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors Reduces Arterial FDG Uptake

Vlachopoulos, Charalambos; Koutagiar, Iosif; Skoumas, Ioannis; Terentes‐Printzios, Dimitrios; Zacharis, E.; Kolovou, Genovefa; Stamatelopoulos, Kimon; Rallidis, Lοukianos S.; Katsiki, Niki; Bilianou, Helen; Liberopoulos, Evangelos; Miliou, Antigoni; Kafouris, Pavlos; Georgakopoulos, A; Gardikioti, Vasiliki; Tousoulis, Dimitrios; Anagnostopoulos, Constantinos

doi:10.1016/j.jcmg.2019.09.024

Cited by 20 publications

(16 citation statements)

References 5 publications

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“…(FDG) positron emission tomography/computed tomography (PET/CT). They found that long-term administration of PCSK9 inhibitor significantly improved arterial inflammation, and that in index vessel, target-to-background ratio (TBR) detected by PET/CT significantly decreased by 0.92 (95% CI: 0.56, 1.28, P < 0.001) (50).…”

Section: Pcsk9 Inhibitors and Inflammation: Clinical And Experimental...mentioning

confidence: 99%

Proprotein Convertase Subtilisin/Kexin Type 9 and Inflammation: An Updated Review

Shi

2022

Front. Cardiovasc. Med.

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The function of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9), a novel plasma protein, has mainly been involved in cholesterol metabolism in the liver, while, more interestingly, recent data have shown that PCSK9 also took part in the modulation of inflammation, which appeared to be another explanation for the reduction of cardiovascular risk by PCSK9 inhibition besides its significant effect on lowering lower-density lipoprotein cholesterol (LDL-C) concentration. Overall, a series of previous studies suggested an association of PCSK9 with inflammation. Firstly, PCSK9 is able to induce the secretion of proinflammatory cytokines in macrophages and in other various tissues and elevated serum PCSK9 levels could be observed in pro-inflammatory conditions, such as sepsis, acute coronary syndrome (ACS). Secondly, detailed signaling pathway studies indicated that PCSK9 positively regulated toll-like receptor 4 expression and inflammatory cytokines expression followed by nuclear factor-kappa B (NF-kB) activation, together with apoptosis and autophagy progression. Besides, PCSK9 enhanced and interacted with scavenger receptors (SRs) of inflammatory mediators like lectin-like oxidized-LDL receptor-1 (LOX-1) to promote inflammatory response. Additionally, several studies also suggested that the role of PCSK9 in atherogenesis was intertwined with inflammation and the interacting effect shown between PCSK9 and LOX-1 was involved in the inflammatory response of atherosclerosis. Finally, emerging clinical trials indicated that PCSK9 inhibitors could reduce more events in patients with ACS accompanied by increased inflammatory status, which might be involved in its attenuating impact on arterial plaque. Hence, further understanding of the relationship between PCSK9 and inflammation would be necessary to help prevent and manage the atherosclerotic cardiovascular disease (ASCVD) clinically. This review article will update the recent advances in the link of PCSK9 with inflammation.

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Section: Pcsk9 Inhibitors and Inflammation: Clinical And Experimental...mentioning

confidence: 99%

Proprotein Convertase Subtilisin/Kexin Type 9 and Inflammation: An Updated Review

Shi

2022

Front. Cardiovasc. Med.

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“…Our study has important clinical implications. PCSK9i reduce effectively cardiovascular outcomes in high-risk patients [23,24] and their role has been upgraded in the recent ESC/EAS Guidelines. However, high-cost is a barrier for their integration in health care systems [12,25].…”

Section: Discussionmentioning

confidence: 99%

Eligibility for PCSK-9 inhibitors treatment in acute coronary syndrome, chronic coronary artery disease and outpatient dyslipidemic patients

et al. 2020

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“…Image acquisition was obtained following recommended protocols and as previously described. 9,10,13 (see Supplemental material). The arterial target-to-background ratio (TBR) was then derived by dividing the mean aortic SUVmax to the average value of venous SUVmean.…”

Section: Methodsmentioning

confidence: 99%

“…7,8 We have shown that aortic FDG uptake is associated with disease severity and response to treatment in patients with lymphoma and hypercholesterolemia. 9,10 There are very few observational studies regarding 18F-FDG PET/CT in COVID-19 affected patients focusing on the lung FDG uptake. 11,12 We investigated the effects of COVID-19 on a vascular level, by assessing 18F-FDG PET/CT uptake in the aorta in patients with severe illness.…”

Section: Introductionmentioning

confidence: 99%

Time-Related Aortic Inflammatory Response, As Assessed With 18F-FDG PET/CT, in Patients Hospitalized With Severe or Critical COVID-19 The COVAIR Study

Vlachopoulos

Printzios

Κatsaounou³

et al. 2021

Preprint

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AimArterial involvement has been implicated in the coronavirus disease of 2019 (COVID-19). 18F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging is a valuable tool for the assessment of disease severity in different types of vasculitis and is a predictor of outcome. We sought to prospectively assess the presence of aortic inflammation and its time-dependent trend by measuring the 18-FDG uptake in PET/CT in patients with severe or critical COVID-19.Methods In this pilot case control study, we recruited 20 patients, who were admitted with severe or critical COVID-19 illness. Patients underwent imaging between 20 to 120 days after hospital admission. Ten age- and sex-matched individuals with prior history of malignancy but free of active disease served as the control group. Arterial inflammation was assessed by measuring 18-FDG uptake in PET/CT and calculating aortic target to blood ratio (TBR).ResultsThere was a significant correlation between aortic TBR values and time distance from diagnosis to 18F-FDG PET/CT scan (-rho- =0.547, p=0.015) even after adjustment for confounders (p=0.002). Patients who were scanned less than 60 days (median) from diagnosis had significantly higher TBR values compared to patients examined more than 60 days post-diagnosis (1.55 [1.47-1.61] vs 1.40 [1.33-1.45], respectively, p=0.013).ConclusionThis is the first study suggesting that 18 FDG PET/CT imaging could be used for assessment of arterial inflammation in patients with severe/critical COVID-19. These findings may have important implications for the understanding of the pathophysiology and the course of the disease and for improving our preventive and therapeutic strategies.

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Long-Term Administration of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors Reduces Arterial FDG Uptake

Cited by 20 publications

References 5 publications

Proprotein Convertase Subtilisin/Kexin Type 9 and Inflammation: An Updated Review

Proprotein Convertase Subtilisin/Kexin Type 9 and Inflammation: An Updated Review

Eligibility for PCSK-9 inhibitors treatment in acute coronary syndrome, chronic coronary artery disease and outpatient dyslipidemic patients

Time-Related Aortic Inflammatory Response, As Assessed With 18F-FDG PET/CT, in Patients Hospitalized With Severe or Critical COVID-19 The COVAIR Study

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