Identification of aspirin resistance using a PDW-miR92a-score

Validation in an intermittent claudication cohort

Helle Glud Binderup*, Kim Houlind, Claus Lohman Brasen, Jonna Skov Madsen

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Objective: Aspirin is a widely used platelet inhibitor to prevent thrombotic events. However, in 25% of patients the antiplatelet effect is insufficient. The current study aimed to validate a newly developed PDW-miR92a-score as a biomarker of the individual response to aspirin enabling targeted antithrombotic therapy. Methods: Blood samples were collected from 209 patients with intermittent claudication on daily aspirin therapy. Based on results from the arachidonic acid stimulated aggregation test, patients were defined as aspirin resistant (n = 92) or responders (n = 117). Using the cut-off values for platelet distribution width (PDW) and plasma levels of microRNA-92a (miR-92a) defined in our pilot study, we investigated the performance of the combined PDW-miR92a-score in the validation study. Furthermore, receiver operating characteristic curve analysis was performed in the validation cohort in order to optimize the cut-off values of the two score parameters. Results: PDW and miR-92a levels were significantly higher in aspirin resistant compared to responding patients. When using the predefined cut-off values for PDW and miR-92a the combined PDW-miR92a score showed high specificity (93.1%) but poor sensitivity (19.8%) for aspirin resistance. By recalculation using new cut-off values identified in the validation cohort, a score with a specificity of 75% and a sensitivity of 54.9% was obtained. Conclusion: Both PDW and plasma levels of miR-92a were confirmed to be significantly higher in aspirin resistant compared to responding patients in our validation cohort. We were, however, unable to confirm the high sensitivity of the combined PDW-miR92a-score previously published by our group in a pilot study.

OriginalsprogEngelsk
TidsskriftClinical Biochemistry
Vol/bind64
Sider (fra-til)30-36
ISSN0009-9120
DOI
StatusUdgivet - feb. 2019

Fingeraftryk

Intermittent Claudication
Platelets
Aspirin
MicroRNAs
Plasmas
Validation Studies
Platelet Aggregation Inhibitors
Biomarkers
Arachidonic Acid
ROC Curve
Blood
Agglomeration

Citer dette

@article{02ea46b7e73e40eeb9d0de706067fc51,
title = "Identification of aspirin resistance using a PDW-miR92a-score: Validation in an intermittent claudication cohort",
abstract = "Objective: Aspirin is a widely used platelet inhibitor to prevent thrombotic events. However, in 25{\%} of patients the antiplatelet effect is insufficient. The current study aimed to validate a newly developed PDW-miR92a-score as a biomarker of the individual response to aspirin enabling targeted antithrombotic therapy. Methods: Blood samples were collected from 209 patients with intermittent claudication on daily aspirin therapy. Based on results from the arachidonic acid stimulated aggregation test, patients were defined as aspirin resistant (n = 92) or responders (n = 117). Using the cut-off values for platelet distribution width (PDW) and plasma levels of microRNA-92a (miR-92a) defined in our pilot study, we investigated the performance of the combined PDW-miR92a-score in the validation study. Furthermore, receiver operating characteristic curve analysis was performed in the validation cohort in order to optimize the cut-off values of the two score parameters. Results: PDW and miR-92a levels were significantly higher in aspirin resistant compared to responding patients. When using the predefined cut-off values for PDW and miR-92a the combined PDW-miR92a score showed high specificity (93.1{\%}) but poor sensitivity (19.8{\%}) for aspirin resistance. By recalculation using new cut-off values identified in the validation cohort, a score with a specificity of 75{\%} and a sensitivity of 54.9{\%} was obtained. Conclusion: Both PDW and plasma levels of miR-92a were confirmed to be significantly higher in aspirin resistant compared to responding patients in our validation cohort. We were, however, unable to confirm the high sensitivity of the combined PDW-miR92a-score previously published by our group in a pilot study.",
keywords = "Anti-platelet therapy, Aspirin resistance, Biomarker, MicroRNA-92a, Platelet distribution width",
author = "Binderup, {Helle Glud} and Kim Houlind and Brasen, {Claus Lohman} and Madsen, {Jonna Skov}",
year = "2019",
month = "2",
doi = "10.1016/j.clinbiochem.2018.12.009",
language = "English",
volume = "64",
pages = "30--36",
journal = "Clinical Biochemistry",
issn = "0009-9120",
publisher = "Elsevier",

}

Identification of aspirin resistance using a PDW-miR92a-score : Validation in an intermittent claudication cohort. / Binderup, Helle Glud; Houlind, Kim; Brasen, Claus Lohman; Madsen, Jonna Skov.

I: Clinical Biochemistry, Bind 64, 02.2019, s. 30-36.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Identification of aspirin resistance using a PDW-miR92a-score

T2 - Validation in an intermittent claudication cohort

AU - Binderup, Helle Glud

AU - Houlind, Kim

AU - Brasen, Claus Lohman

AU - Madsen, Jonna Skov

PY - 2019/2

Y1 - 2019/2

N2 - Objective: Aspirin is a widely used platelet inhibitor to prevent thrombotic events. However, in 25% of patients the antiplatelet effect is insufficient. The current study aimed to validate a newly developed PDW-miR92a-score as a biomarker of the individual response to aspirin enabling targeted antithrombotic therapy. Methods: Blood samples were collected from 209 patients with intermittent claudication on daily aspirin therapy. Based on results from the arachidonic acid stimulated aggregation test, patients were defined as aspirin resistant (n = 92) or responders (n = 117). Using the cut-off values for platelet distribution width (PDW) and plasma levels of microRNA-92a (miR-92a) defined in our pilot study, we investigated the performance of the combined PDW-miR92a-score in the validation study. Furthermore, receiver operating characteristic curve analysis was performed in the validation cohort in order to optimize the cut-off values of the two score parameters. Results: PDW and miR-92a levels were significantly higher in aspirin resistant compared to responding patients. When using the predefined cut-off values for PDW and miR-92a the combined PDW-miR92a score showed high specificity (93.1%) but poor sensitivity (19.8%) for aspirin resistance. By recalculation using new cut-off values identified in the validation cohort, a score with a specificity of 75% and a sensitivity of 54.9% was obtained. Conclusion: Both PDW and plasma levels of miR-92a were confirmed to be significantly higher in aspirin resistant compared to responding patients in our validation cohort. We were, however, unable to confirm the high sensitivity of the combined PDW-miR92a-score previously published by our group in a pilot study.

AB - Objective: Aspirin is a widely used platelet inhibitor to prevent thrombotic events. However, in 25% of patients the antiplatelet effect is insufficient. The current study aimed to validate a newly developed PDW-miR92a-score as a biomarker of the individual response to aspirin enabling targeted antithrombotic therapy. Methods: Blood samples were collected from 209 patients with intermittent claudication on daily aspirin therapy. Based on results from the arachidonic acid stimulated aggregation test, patients were defined as aspirin resistant (n = 92) or responders (n = 117). Using the cut-off values for platelet distribution width (PDW) and plasma levels of microRNA-92a (miR-92a) defined in our pilot study, we investigated the performance of the combined PDW-miR92a-score in the validation study. Furthermore, receiver operating characteristic curve analysis was performed in the validation cohort in order to optimize the cut-off values of the two score parameters. Results: PDW and miR-92a levels were significantly higher in aspirin resistant compared to responding patients. When using the predefined cut-off values for PDW and miR-92a the combined PDW-miR92a score showed high specificity (93.1%) but poor sensitivity (19.8%) for aspirin resistance. By recalculation using new cut-off values identified in the validation cohort, a score with a specificity of 75% and a sensitivity of 54.9% was obtained. Conclusion: Both PDW and plasma levels of miR-92a were confirmed to be significantly higher in aspirin resistant compared to responding patients in our validation cohort. We were, however, unable to confirm the high sensitivity of the combined PDW-miR92a-score previously published by our group in a pilot study.

KW - Anti-platelet therapy

KW - Aspirin resistance

KW - Biomarker

KW - MicroRNA-92a

KW - Platelet distribution width

U2 - 10.1016/j.clinbiochem.2018.12.009

DO - 10.1016/j.clinbiochem.2018.12.009

M3 - Journal article

VL - 64

SP - 30

EP - 36

JO - Clinical Biochemistry

JF - Clinical Biochemistry

SN - 0009-9120

ER -