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dc.contributor.authorNayor, Matthew
dc.contributor.authorShort, Meghan I.
dc.contributor.authorRasheed, Humaira
dc.contributor.authorLin, Honghuang
dc.contributor.authorJonasson, Christian
dc.contributor.authorYang, Qiong
dc.contributor.authorHveem, Kristian
dc.contributor.authorFelix, Janine F.
dc.contributor.authorMorrison, Alanna C.
dc.contributor.authorWild, Philipp S.
dc.contributor.authorMorley, Michael P.
dc.contributor.authorCappola, Thomas P.
dc.contributor.authorBenson, Mark D.
dc.contributor.authorNgo, Debby
dc.contributor.authorSinha, Sumita
dc.contributor.authorKeyes, Michelle J.
dc.contributor.authorShen, Dongxiao
dc.contributor.authorWang, Thomas J.
dc.contributor.authorLarson, Martin G.
dc.contributor.authorBrumpton, Ben Michael
dc.contributor.authorGerszten, Robert E.
dc.contributor.authorOmland, Torbjørn
dc.contributor.authorVasan, Ramachandran S.
dc.date.accessioned2021-09-02T11:11:31Z
dc.date.available2021-09-02T11:11:31Z
dc.date.created2020-05-23T18:25:23Z
dc.date.issued2020
dc.identifier.issn1941-3289
dc.identifier.urihttps://hdl.handle.net/11250/2772540
dc.description.abstractAbstract Background: We used a large-scale, high-throughput DNA aptamer-based discovery proteomic platform to identify circulating biomarkers of cardiac remodeling and incident heart failure (HF) in community-dwelling individuals. Methods: We evaluated 1895 FHS (Framingham Heart Study) participants (age 55±10 years, 54% women) who underwent proteomic profiling and echocardiography. Plasma levels of 1305 proteins were related to echocardiographic traits and to incident HF using multivariable regression. Statistically significant protein-HF associations were replicated in the HUNT (Nord-Trøndelag Health) study (n=2497, age 63±10 years, 43% women), and results were meta-analyzed. Genetic variants associated with circulating protein levels (pQTLs) were related to echocardiographic traits in the EchoGen (n=30 201) and to incident HF in the CHARGE (n=20 926) consortia. Results: Seventeen proteins associated with echocardiographic traits in cross-sectional analyses (false discovery rate <0.10), and 8 of these proteins had pQTLs associated with echocardiographic traits in EchoGen (P<0.0007). In Cox models adjusted for clinical risk factors, 29 proteins demonstrated associations with incident HF in FHS (174 HF events, mean follow-up 19 [limits, 0.2–23.7] years). In meta-analyses of FHS and HUNT, 6 of these proteins were associated with incident HF (P<3.8×10−5; 3 with higher risk: NT-proBNP [N-terminal proB-type natriuretic peptide], TSP2 [thrombospondin-2], MBL [mannose-binding lectin]; and 3 with lower risk: ErbB1 [epidermal growth factor receptor], GDF-11/8 [growth differentiation factor-11/8], and RGMC [hemojuvelin]). For 5 of the 6 proteins, pQTLs were associated with echocardiographic traits (P<0.0006) in EchoGen, and for RGMC, a protein quantitative trait loci was associated with incident HF (P=0.001). Conclusions: A large-scale proteomics approach identified new predictors of cardiac remodeling and incident HF. Future studies are warranted to elucidate how biological pathways represented by these proteins may mediate cardiac remodeling and HF risk and to assess if these proteins can improve HF risk prediction.en_US
dc.language.isoengen_US
dc.publisherAmerican Heart Associationen_US
dc.titleAptamer-Based Proteomic Platform Identifies Novel Protein Predictors of Incident Heart Failure and Echocardiographic Traitsen_US
dc.typePeer revieweden_US
dc.typeJournal articleen_US
dc.description.versionpublishedVersionen_US
dc.source.volume13en_US
dc.source.journalCirculation: Heart Failureen_US
dc.source.issue5en_US
dc.identifier.doi10.1161/CIRCHEARTFAILURE.119.006749
dc.identifier.cristin1812249
dc.relation.projectNorges forskningsråd: 248817en_US
dc.relation.projectStiftelsen Kristian Gerhard Jebsen: SKGJ-MED-015en_US
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1


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