eRapport

Improving risk prediction of myocardial infarction by including new types of circulating biomarkers

Prosjekt
Prosjektnummer
46055600-152
Ansvarlig person
Anja Bye
Institusjon
NTNU, MH-fakultetet, Institutt for sirkulasjon og bildediagnostikk (ISB)
Prosjektkategori
Korttidsprosjekt (Felles Forskningsutvalg)
Helsekategori
Cardiovascular
Forskningsaktivitet
3. Prevention, 4. Detection and Diagnosis
Rapporter
2022 - sluttrapport
Vi har gjennomført flere forskjellige metodeuttestinger for microRNA analyse i samarbeid med lokale og internasjonale samarbeidspartnere. Utviklingen på feltet går raskt, og vi vurderer nå å teste ut en ny metode for microRNA kvantifisering. Det viktigste fremover vil være å fortsatt jobbe videre med standardisering av analyser, samt å identifisere robuste og reproduserbre microRNA markører innen forebygging og diagnostikk av hjertesykdom. Vi har publisert 4 artikler om microRNA som risikomarkører for sykdom siden tildelingstidspunkt, samt at vi har en artikkel som er inne til vurdering, og 2 artikler som vil bli sendt inn i løpet av våren 2023. Vi er sånn sett svært fornøyd med hva vi har fått ut av denne viktige bevilgningen, og vi har tro på at vi har bidratt signifikant inn mot at microRNA kan bli implementert i klinisk bruk om noen år. På sikt tror vi at microRNA kan implementeres i klinikken innen forebygging og diagnostisering av flere sykdommer. Vi har spesielt tro på at disse nye biomarkørene kan supplere andre tradisjonelle biomarkører i risikoprediksjon, men også for diagnose og prognose. Det er mye som nå tyder på at microRNA kan være kjønnsspesifikke risikofaktorer. Utfordringen ligger nå spesielt på at metoder for analysering av microRNA må standardiseres over hele verden.
2021
microRNAs (miRs) have emerged as promising new risk markers of cardiovascular disease (CVD). As miR-analyses are expensive, we want to establish a cost-efficient method for quantification of miRs in blood using less material and improving reproducibility. Furthermore, we will determine whether incorporation of miRs can improve CVD risk prediction.CVD is the leading cause of death globally, and the number of individuals at risk is expected to increase in the years to come. Hence, it will be increasingly important for the healthcare system to identify individuals at high risk for CVD, to initiate cost-efficient prevention strategies as lifestyle interventions and pharmacotherapy to decrease the number of events and hospitalization. In the clinical setting, risk prediction models are available for determining the 10-year risk of CVD. However, the currently available risk prediction models only explain a modest proportion of the incidence, and currently fail to discover 15-20 % of the individuals at risk for CVD. Thus, there is a clinical need for new risk markers that could complement the assessment of traditional risk factors, to identify the individuals at risk with greater precision than today. During the last years, microRNAs (miRs) have emerged as promising new risk markers of CVD. We have, as one of few research groups around the world, explored their potential to improve risk prediction models for myocardial infarction (MI), and have reported very promising results. As miR-analyses are expensive, we want to establish a more cost-efficient method for quantification of circulating miRs in blood using less material and improving reproducibility. Furthermore, we will determine whether incorporation of candidate miRs can improve the precision of the NORRISK2 score to predict 10-year risk of MI. Aim1. Establish new cost-efficient, ultra-sensitive methodology for quantification of circulating microRNAs at St.Olavs University Hospital. Status (February 2022): We have tested droplet digital PCR for analysis of microRNAs in blood. The method shows promising technical results for most of the microRNAs tested. However, the currently available droplet generator limits the possibilities of high-throughput analyses. We are therefore currently testing next-generation sequencing. As microRNA sequencing is expensive, we have approached several laboratories for quotes. Due to the more expensive analyses we would like to perform at least one pilot study in a limited number of participants before using precious blood samples from HUNT. As for now, we are applying RT-PCR analyses for the microRNA studies, but closely monitor the technical development. Aim 2. Determine whether adding information on microRNA-levels can improve the precision of the NORRISK2 score to predict myocardial infarction Status (February 2022): We have published two new papers on microRNAs and CVD, and is currently working on a new paper testing the potential for microRNAs to improve risk prediction for myocardial infarction in a cohort of 300 participant from HUNT. The results are promising, and we are hoping to present results at two international conferences during 2022.

På sikt tror vi at microRNA kan implementeres i klinikken innen forebygging og diagnostisering av flere sykdommer. Vi har spesielt tro på at disse nye biomarkørene kan supplere andre tradisjonelle biomarkører i risikoprediksjon, men også for diagnose og prognose. Det er mye som nå tyder på at microRNA kan være kjønnsspesifikke risikofaktorer. Utfordringen ligger nå spesielt på at metoder for analysering av microRNA må standardiseres over hele verden.

2020
microRNAs (miRs) have emerged as promising new risk markers of cardiovascular disease (CVD). As miR-analyses are expensive, we want to establish a cost-efficient method for quantification of miRs in blood using less material and improving reproducibility. Furthermore, we will determine whether incorporation of miRs can improve CVD risk prediction.CVD is the leading cause of death globally, and the number of individuals at risk is expected to increase in the years to come. Hence, it will be increasingly important for the healthcare system to identify individuals at high risk for CVD, to initiate cost-efficient prevention strategies as lifestyle interventions and pharmacotherapy to decrease the number of events and hospitalization. In the clinical setting, risk prediction models are available for determining the 10-year risk of CVD. However, the currently available risk prediction models only explain a modest proportion of the incidence, and currently fail to discover 15-20 % of the individuals at risk for CVD. Thus, there is a clinical need for new risk markers that could complement the assessment of traditional risk factors, to identify the individuals at risk with greater precision than today. During the last years, microRNAs (miRs) have emerged as promising new risk markers of CVD. We have, as one of few research groups around the world, explored their potential to improve risk prediction models for myocardial infarction (MI), and have reported very promising results. As miR-analyses are expensive, we want to establish a more cost-efficient method for quantification of circulating miRs in blood using less material and improving reproducibility. Furthermore, we will determine whether incorporation of candidate miRs can improve the precision of the NORRISK2 score to predict 10-year risk of MI. Aim1. Establish new cost-efficient, ultra-sensitive methodology for quantification of circulating microRNAs at St.Olavs University Hospital. Status (February 2021): We have tested droplet digital PCR for analysis of microRNAs in blood. The method shows promising technical results for most of the microRNAs tested. However, the currently availible droplet generator limits the possibilities of high-throuhput analyses. We are therefore currently testing next-generation sequencing. We still believe that ddPCR will be the optimal choise for clinical utilisation applying ddPCR equipment better suited for high-throughput analysis. Aim 2. Determine whether adding information on microRNA-levels can improve the precision of the NORRISK2 score to predict myocardial infarction Status (February 2020): We have published two papers testing during the last year reporting the potential of microRNAs in risk prediction of CVD. The results are promising, and we are hoping to present results at 2 conferences during 2021.

På sikt tror vi at microRNA kan implementeres i klinikken innen forebygging og diagnostisering av flere sykdommer. Vi har spesielt tro på at disse nye biomarkørene kan supplere andre tradisjonelle biomarkører. Utfordringen ligger nå spesielt på at metoder for analysering av microRNA må standardiseres over hele verden.

2019
microRNAs (miRs) have emerged as promising new risk markers of CVD. As miR-analyses are expensive, we want to establish a cost-efficient method for quantification of miRs in blood using less material and improving reproducibility. Furthermore, we will determine whether incorporation of miRs can improve risk prediction for myocardial infarction.Cardiovascular disease (CVD) is the leading cause of death globally, and the number of individuals at risk is expected to increase in the years to come. Hence, it will be increasingly important for the healthcare system to identify individuals at high risk for CVD, to initiate cost-efficient prevention strategies as lifestyle interventions and pharmacotherapy to decrease the number of events and hospitalization. In the clinical setting, risk prediction models are available for determining the 10-year risk of CVD. However, the currently available risk prediction models only explain a modest proportion of the incidence, and currently fail to discover 15-20 % of the individuals at risk for CVD. Thus, there is a clinical need for new risk markers that could complement the assessment of traditional risk factors, to identify the individuals at risk with greater precision than today. During the last years, microRNAs (miRs) have emerged as promising new risk markers of CVD. We have, as one of few research groups around the world, explored their potential to improve risk prediction models for myocardial infarction (MI), and have reported very promising results. As miR-analyses are expensive, we want to establish a more cost-efficient method for quantification of circulating miRs in blood using less material and improving reproducibility. Furthermore, we will determine whether incorporation of candidate miRs can improve the precision of the NORRISK2 score to predict 10-year risk of MI. Primary aims 1. Establish new cost-efficient, ultra-sensitive methodology for quantification of circulating microRNAs at St.Olavs University Hospital. Status (february 2020): We are currently testing using droplet digital PCR for analysis of microRNAs in blood. The method shows promising results for the microRNAs that we have tested so far, in collaboration with SINTEF. Due to the use of a droplet generator, quantifying large sample volumes might be an issue, however, NINA (in Trondheim) has a method that would allow for high-throughput analysis. We will continue to work on establishing this method in our lab. 2. Determine whether adding information on microRNA-levels can improve the precision of the NORRISK2 score to predict myocardial infarction Status (february 2020): We have so far published two papers testing the potential of improving precision of currently available risk prediction algorithms for myocardial infarction. A new paper was published in February 2020 in collaboration with researchers at Karolinska Institutet. The results are promising, and we are planning to present results at 3 conferences during 2020. We will also be submitting a new paper on microRNAs in risk prediction togheter with our collegues at Department of Cardiology, St.Olavs hospital during 2020.

Sirkulerende microRNA som biomarkører for sykdom er et spennende og lovende forskningsfelt. Da microRNA slippes ut fra sykt vev og har en svært god stabilitet i blod, tenker vi at man kan finne en microRNA signatur som reflekterer tilstedeværelse av åreforkalkninger. Det har vært mange metodologiske utfordringer med analyse og kvantifisering av microRNA-nivåer i blod, tross flere år med forskning. Nylig kom det et nytt system som kalles droplet-digital PCR som kan vise seg å være svært aktuelt for å forbedre metodene for kvantifisering av microRNA i blod. Vi ønsker å teste og optimalisere dette systemet for å se på mulighetene for at man i fremtiden kan få slike analyser inn i klinisk praksis. Dette vil være uavhengig av type sykdom, og kan komme til å bli en viktig metode også innen kreftforskning. Derfor har vi tro på at metodologiske studier på microRNA-kvantifisering vha droplet-digital PCR kan bli viktig for fremtidig helsetjeneste når det gjelder deteksjon, forebygging og behandling av sykdommer hvor microRNA i blod representerer potensielle biomarkører.

Vitenskapelige artikler
Taraldsen MD, Wiseth R, Videm V, Bye A, Madssen E

Associations between circulating microRNAs and coronary plaque characteristics: potential impact from physical exercise.

Physiol Genomics 2022 Apr 01;54(4):129. Epub 2022 feb 28

PMID: 35226566

Rutkovskiy A, Lyngbakken MN, Dahl MB, Bye A, Pedersen MH, Wisløff U, Christensen G, Høiseth AD, Omland T, Røsjø H

Circulating MicroRNA-210 Concentrations in Patients with Acute Heart Failure: Data from the Akershus Cardiac Examination 2 Study.

Clin Chem 2021 06 01;67(6):889-898.

PMID: 33783502

Gigante B, Papa L, Bye A, Kunderfranco P, Viviani C, Roncarati R, Briguori C, de Faire U, Bottai M, Condorelli G

MicroRNA signatures predict early major coronary events in middle-aged men and women.

Cell Death Dis 2020 01 30;11(1):74. Epub 2020 jan 30

PMID: 32001669

Velle-Forbord T, Eidlaug M, Debik J, Sæther JC, Follestad T, Nauman J, Gigante B, Røsjø H, Omland T, Langaas M, Bye A

Circulating microRNAs as predictive biomarkers of myocardial infarction: Evidence from the HUNT study.

Atherosclerosis 2019 Oct;289():1-7. Epub 2019 jul 26

PMID: 31437610

Taraldsen MD, Wiseth R, Videm V, Bye A, Madssen M.

Associations between circulating microRNAs and coronary plaque characteristics: potential impact from physical exercise

Physiological Genomics, 2022

Deltagere
  • Maria Dalen Taraldsen Prosjektdeltaker
  • Atle Wiig-Fisketjøn Prosjektdeltaker
  • Gianluigi Condorelli Prosjektdeltaker
  • Bruna Gigante Prosjektdeltaker
  • Turid Follestad Prosjektdeltaker
  • Tonje Marita Bjerkan Heggeset Prosjektdeltaker
  • Mette Langaas Prosjektdeltaker
  • Torbjørn Omland Prosjektdeltaker
  • Helge Røsjø Prosjektdeltaker
  • Erik Madssen Medveileder, biveileder
  • Elisabeth Kleivhaug Vesterbekkmo Prosjektdeltaker
  • Rune Wiseth Prosjektdeltaker
  • Julie Caroline Sæther Doktorgradsstipendiat
  • Anja Bye Prosjektleder

eRapport er utarbeidet av Sølvi Lerfald og Reidar Thorstensen, Regionalt kompetansesenter for klinisk forskning, Helse Vest RHF, og videreutvikles av de fire RHF-ene i fellesskap, med støtte fra Helse Vest IKT

Alle henvendelser rettes til Helse Midt-Norge RHF - Samarbeidsorganet og FFU

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