title: Novel methodologies for biomarker discovery in atherosclerosis.
abstract: Identification of subjects at increased risk for cardiovascular events plays a central role in the worldwide efforts to improve prevention, prediction, diagnosis, and prognosis of cardiovascular disease and to decrease the related costs. Despite their high predictive value on population level, traditional risk factors fail to fully predict individual risk. This position paper provides a summary of current vascular biomarkers other than the traditional risk factors with a special focus on the emerging -omics technologies. The definition of biomarkers and the identification and use of classical biomarkers are introduced, and we discuss the limitations of current biomarkers such as high sensitivity C-reactive protein (hsCRP) or N-terminal pro-brain natriuretic peptide (NT-proBNP). This is complemented by circulating plasma biomarkers, including high-density lipoprotein (HDL), and the conceptual shift from HDL cholesterol levels to HDL composition/function for cardiovascular risk assessment. Novel sources for plasma-derived markers include microparticles, microvesicles, and exosomes and their use for current omics-based analytics. Measurement of circulating micro-RNAs, short RNA sequences regulating gene expression, has attracted major interest in the search for novel biomarkers. Also, mass spectrometry and nuclear magnetic resonance spectroscopy have become key complementary technologies in the search for new biomarkers, such as proteomic searches or identification and quantification of small metabolites including lipids (metabolomics and lipidomics). In particular, pro-inflammatory lipid metabolites have gained much interest in the cardiovascular field. Our consensus statement concludes on leads and needs in biomarker research for the near future to improve individual cardiovascular risk prediction.
authors.affiliation: Laboratory of Experimental Cardiology and Laboratory of Clinical Chemistry and Haematology, University Medical Centre Utrecht, Utrecht, Netherlands i.hoefer@umcutrecht.nl sabine.steffens@med.uni-muenchen.de.
authors.forename: Imo E
authors.initials: IE
authors.lastname: Hoefer
authors.affiliation: Ludwig-Maximilians-University, G02.523, Heidelberglaan 100, 3584CX Munich, Germany German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany i.hoefer@umcutrecht.nl sabine.steffens@med.uni-muenchen.de.
authors.forename: Sabine
authors.initials: S
authors.lastname: Steffens
authors.affiliation: University of Oulu, Oulu, Finland University of Bristol, Bristol, UK.
authors.forename: Mika
authors.initials: M
authors.lastname: Ala-Korpela
authors.affiliation: Karolinska Institutet, Stockholm, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Bäck
authors.affiliation: Cardiovascular Research Center, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain.
authors.forename: Lina
authors.initials: L
authors.lastname: Badimon
authors.affiliation: University of Geneva, Geneva, Switzerland.
authors.forename: Marie-Luce
authors.initials: ML
authors.lastname: Bochaton-Piallat
authors.affiliation: INSERM, U970, Paris Cardiovascular Research Center, Paris, France.
authors.forename: Chantal M
authors.initials: CM
authors.lastname: Boulanger
authors.affiliation: Bichat Hospital, Paris, France.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Caligiuri
authors.affiliation: University of Frankfurt, Frankfurt, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dimmeler
authors.affiliation: IIS-Fundación Jiménez Díaz-UAM, Madrid, Spain.
authors.forename: Jesus
authors.initials: J
authors.lastname: Egido
authors.affiliation: University of Sheffield, Sheffield, UK.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Evans
authors.affiliation: Jagiellonian University, Krakow, Poland University of Glasgow, Glasgow, UK.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Guzik
authors.affiliation: University of Geneva, Geneva, Switzerland.
authors.forename: Brenda R
authors.initials: BR
authors.lastname: Kwak
authors.affiliation: University Hospital Zurich, Zurich, Switzerland.
authors.forename: Ulf
authors.initials: U
authors.lastname: Landmesser
authors.affiliation: British Heart Foundation Centre, King's College London, London, UK.
authors.forename: Manuel
authors.initials: M
authors.lastname: Mayr
authors.affiliation: University of Oxford, Oxford, UK.
authors.forename: Claudia
authors.initials: C
authors.lastname: Monaco
authors.affiliation: Laboratory of Experimental Cardiology and Laboratory of Clinical Chemistry and Haematology, University Medical Centre Utrecht, Utrecht, Netherlands.
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
authors.affiliation: IIS-Fundación Jiménez Díaz-UAM, Madrid, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Tuñón
authors.affiliation: Ludwig-Maximilians-University, G02.523, Heidelberglaan 100, 3584CX Munich, Germany German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
mesh_terms: D050197:Atherosclerosis / Q000175:diagnosis*; D015415:Biomarkers / Q000097:blood*; D055252:Cell-Derived Microparticles / Q000378:metabolism; D002623:Chemistry Techniques, Analytical / Q000639:trends; D032921:Consensus; D003327:Coronary Disease / Q000175:diagnosis; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood; D055432:Metabolomics / Q000639:trends; D035683:MicroRNAs / Q000097:blood; D040901:Proteomics / Q000639:trends; D018570:Risk Assessment / Q000639:trends; D049490:Systems Biology / Q000639:trends
chemical_list: D015415:Biomarkers; D008075:Lipoproteins, HDL; D035683:MicroRNAs
keywords: Atherosclerosis; Clinical biomarker; HDL; Mass spectrometry; Micro-RNA; Risk prediction; Systems biology