An integrated signature of extracellular matrix proteins and a diastolic function imaging parameter predicts post-MI long-term outcomes
BackgroundPatients suffering from acute myocardial infarction (AMI) are at risk of secondary outcomes including major adverse cardiovascular events (MACE) and heart failure (HF). Comprehensive molecular phenotyping and cardiac imaging during the post-discharge time window may provide cues for risk s...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-04-01
|
| Series: | Frontiers in Cardiovascular Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1123682/full |
| _version_ | 1797847927841882112 |
|---|---|
| author | Hiromi W.L. Koh Hiromi W.L. Koh Anna P. Pilbrow Sock Hwee Tan Sock Hwee Tan Qing Zhao Peter I. Benke Bo Burla Federico Torta Federico Torta John W. Pickering Richard Troughton Christopher Pemberton Wern-Miin Soo Wern-Miin Soo Lieng Hsi Ling Lieng Hsi Ling Robert N. Doughty Hyungwon Choi Markus R. Wenk Markus R. Wenk A. Mark Richards A. Mark Richards A. Mark Richards Mark Y. Chan Mark Y. Chan |
| author_facet | Hiromi W.L. Koh Hiromi W.L. Koh Anna P. Pilbrow Sock Hwee Tan Sock Hwee Tan Qing Zhao Peter I. Benke Bo Burla Federico Torta Federico Torta John W. Pickering Richard Troughton Christopher Pemberton Wern-Miin Soo Wern-Miin Soo Lieng Hsi Ling Lieng Hsi Ling Robert N. Doughty Hyungwon Choi Markus R. Wenk Markus R. Wenk A. Mark Richards A. Mark Richards A. Mark Richards Mark Y. Chan Mark Y. Chan |
| author_sort | Hiromi W.L. Koh |
| collection | DOAJ |
| description | BackgroundPatients suffering from acute myocardial infarction (AMI) are at risk of secondary outcomes including major adverse cardiovascular events (MACE) and heart failure (HF). Comprehensive molecular phenotyping and cardiac imaging during the post-discharge time window may provide cues for risk stratification for the outcomes.Materials and methodsIn a prospective AMI cohort in New Zealand (N = 464), we measured plasma proteins and lipids 30 days after hospital discharge and inferred a unified partial correlation network with echocardiographic variables and established clinical biomarkers (creatinine, c-reactive protein, cardiac troponin I and natriuretic peptides). Using a network-based data integration approach (iOmicsPASS+), we identified predictive signatures of long-term secondary outcomes based on plasma protein, lipid, imaging markers and clinical biomarkers and assessed the prognostic potential in an independent cohort from Singapore (N = 190).ResultsThe post-discharge levels of plasma proteins and lipids showed strong correlations within each molecular type, reflecting concerted homeostatic regulation after primary MI events. However, the two molecular types were largely independent with distinct correlation structures with established prognostic imaging parameters and clinical biomarkers. To deal with massively correlated predictive features, we used iOmicsPASS + to identify subnetwork signatures of 211 and 189 data features (nodes) predictive of MACE and HF events, respectively (160 overlapping). The predictive features were primarily imaging parameters, including left ventricular and atrial parameters, tissue Doppler parameters, and proteins involved in extracellular matrix (ECM) organization, cell differentiation, chemotaxis, and inflammation. The network signatures contained plasma protein pairs with area-under-the-curve (AUC) values up to 0.74 for HF prediction in the validation cohort, but the pair of NT-proBNP and fibulin-3 (EFEMP1) was the best predictor (AUC = 0.80). This suggests that there were a handful of plasma proteins with mechanistic and functional roles in predisposing patients to the secondary outcomes, although they may be weaker prognostic markers than natriuretic peptides individually. Among those, the diastolic function parameter (E/e' - an indicator of left ventricular filling pressure) and two ECM proteins, EFEMP1 and follistatin-like 3 (FSTL3) showed comparable performance to NT-proBNP and outperformed left ventricular measures as benchmark prognostic factors for post-MI HF.ConclusionPost-discharge levels of E/e', EFEMP1 and FSTL3 are promising complementary markers of secondary adverse outcomes in AMI patients. |
| first_indexed | 2024-04-09T18:19:10Z |
| format | Article |
| id | doaj.art-b8f723c535b84f859a7ca0e4a88409b3 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-04-09T18:19:10Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-b8f723c535b84f859a7ca0e4a88409b32023-04-12T14:19:45ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2023-04-011010.3389/fcvm.2023.11236821123682An integrated signature of extracellular matrix proteins and a diastolic function imaging parameter predicts post-MI long-term outcomesHiromi W.L. Koh0Hiromi W.L. Koh1Anna P. Pilbrow2Sock Hwee Tan3Sock Hwee Tan4Qing Zhao5Peter I. Benke6Bo Burla7Federico Torta8Federico Torta9John W. Pickering10Richard Troughton11Christopher Pemberton12Wern-Miin Soo13Wern-Miin Soo14Lieng Hsi Ling15Lieng Hsi Ling16Robert N. Doughty17Hyungwon Choi18Markus R. Wenk19Markus R. Wenk20A. Mark Richards21A. Mark Richards22A. Mark Richards23Mark Y. Chan24Mark Y. Chan25Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeInstitute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeDepartment of Medicine, Christchurch Heart Institute, University of Otago, Christchurch, New ZealandDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeNational University Heart Centre, National University Health System, Singapore, SingaporeDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeSingapore Lipidomics Incubator (SLING), Life Sciences Institute, National University of Singapore, Singapore, SingaporeSingapore Lipidomics Incubator (SLING), Life Sciences Institute, National University of Singapore, Singapore, SingaporeSingapore Lipidomics Incubator (SLING), Life Sciences Institute, National University of Singapore, Singapore, SingaporePrecision Medicine Translational Research Programme and Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeDepartment of Medicine, Christchurch Heart Institute, University of Otago, Christchurch, New ZealandDepartment of Medicine, Christchurch Heart Institute, University of Otago, Christchurch, New ZealandDepartment of Medicine, Christchurch Heart Institute, University of Otago, Christchurch, New ZealandDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeNational University Heart Centre, National University Health System, Singapore, SingaporeDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeNational University Heart Centre, National University Health System, Singapore, SingaporeHeart Health Research Group, University of Auckland, Auckland, New ZealandDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeSingapore Lipidomics Incubator (SLING), Life Sciences Institute, National University of Singapore, Singapore, SingaporePrecision Medicine Translational Research Programme and Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeDepartment of Medicine, Christchurch Heart Institute, University of Otago, Christchurch, New ZealandNational University Heart Centre, National University Health System, Singapore, SingaporeDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeNational University Heart Centre, National University Health System, Singapore, SingaporeBackgroundPatients suffering from acute myocardial infarction (AMI) are at risk of secondary outcomes including major adverse cardiovascular events (MACE) and heart failure (HF). Comprehensive molecular phenotyping and cardiac imaging during the post-discharge time window may provide cues for risk stratification for the outcomes.Materials and methodsIn a prospective AMI cohort in New Zealand (N = 464), we measured plasma proteins and lipids 30 days after hospital discharge and inferred a unified partial correlation network with echocardiographic variables and established clinical biomarkers (creatinine, c-reactive protein, cardiac troponin I and natriuretic peptides). Using a network-based data integration approach (iOmicsPASS+), we identified predictive signatures of long-term secondary outcomes based on plasma protein, lipid, imaging markers and clinical biomarkers and assessed the prognostic potential in an independent cohort from Singapore (N = 190).ResultsThe post-discharge levels of plasma proteins and lipids showed strong correlations within each molecular type, reflecting concerted homeostatic regulation after primary MI events. However, the two molecular types were largely independent with distinct correlation structures with established prognostic imaging parameters and clinical biomarkers. To deal with massively correlated predictive features, we used iOmicsPASS + to identify subnetwork signatures of 211 and 189 data features (nodes) predictive of MACE and HF events, respectively (160 overlapping). The predictive features were primarily imaging parameters, including left ventricular and atrial parameters, tissue Doppler parameters, and proteins involved in extracellular matrix (ECM) organization, cell differentiation, chemotaxis, and inflammation. The network signatures contained plasma protein pairs with area-under-the-curve (AUC) values up to 0.74 for HF prediction in the validation cohort, but the pair of NT-proBNP and fibulin-3 (EFEMP1) was the best predictor (AUC = 0.80). This suggests that there were a handful of plasma proteins with mechanistic and functional roles in predisposing patients to the secondary outcomes, although they may be weaker prognostic markers than natriuretic peptides individually. Among those, the diastolic function parameter (E/e' - an indicator of left ventricular filling pressure) and two ECM proteins, EFEMP1 and follistatin-like 3 (FSTL3) showed comparable performance to NT-proBNP and outperformed left ventricular measures as benchmark prognostic factors for post-MI HF.ConclusionPost-discharge levels of E/e', EFEMP1 and FSTL3 are promising complementary markers of secondary adverse outcomes in AMI patients.https://www.frontiersin.org/articles/10.3389/fcvm.2023.1123682/fullintegrative analysismulti-omicsechocardiogaphymajor adverse cardiac events (MACE)heart failure hospitalization |
| spellingShingle | Hiromi W.L. Koh Hiromi W.L. Koh Anna P. Pilbrow Sock Hwee Tan Sock Hwee Tan Qing Zhao Peter I. Benke Bo Burla Federico Torta Federico Torta John W. Pickering Richard Troughton Christopher Pemberton Wern-Miin Soo Wern-Miin Soo Lieng Hsi Ling Lieng Hsi Ling Robert N. Doughty Hyungwon Choi Markus R. Wenk Markus R. Wenk A. Mark Richards A. Mark Richards A. Mark Richards Mark Y. Chan Mark Y. Chan An integrated signature of extracellular matrix proteins and a diastolic function imaging parameter predicts post-MI long-term outcomes Frontiers in Cardiovascular Medicine integrative analysis multi-omics echocardiogaphy major adverse cardiac events (MACE) heart failure hospitalization |
| title | An integrated signature of extracellular matrix proteins and a diastolic function imaging parameter predicts post-MI long-term outcomes |
| title_full | An integrated signature of extracellular matrix proteins and a diastolic function imaging parameter predicts post-MI long-term outcomes |
| title_fullStr | An integrated signature of extracellular matrix proteins and a diastolic function imaging parameter predicts post-MI long-term outcomes |
| title_full_unstemmed | An integrated signature of extracellular matrix proteins and a diastolic function imaging parameter predicts post-MI long-term outcomes |
| title_short | An integrated signature of extracellular matrix proteins and a diastolic function imaging parameter predicts post-MI long-term outcomes |
| title_sort | integrated signature of extracellular matrix proteins and a diastolic function imaging parameter predicts post mi long term outcomes |
| topic | integrative analysis multi-omics echocardiogaphy major adverse cardiac events (MACE) heart failure hospitalization |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1123682/full |
| work_keys_str_mv | AT hiromiwlkoh anintegratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT hiromiwlkoh anintegratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT annappilbrow anintegratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT sockhweetan anintegratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT sockhweetan anintegratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT qingzhao anintegratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT peteribenke anintegratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT boburla anintegratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT federicotorta anintegratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT federicotorta anintegratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT johnwpickering anintegratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT richardtroughton anintegratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT christopherpemberton anintegratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT wernmiinsoo anintegratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT wernmiinsoo anintegratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT lienghsiling anintegratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT lienghsiling anintegratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT robertndoughty anintegratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT hyungwonchoi anintegratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT markusrwenk anintegratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT markusrwenk anintegratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT amarkrichards anintegratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT amarkrichards anintegratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT amarkrichards anintegratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT markychan anintegratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT markychan anintegratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT hiromiwlkoh integratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT hiromiwlkoh integratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT annappilbrow integratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT sockhweetan integratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT sockhweetan integratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT qingzhao integratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT peteribenke integratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT boburla integratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT federicotorta integratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT federicotorta integratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT johnwpickering integratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT richardtroughton integratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT christopherpemberton integratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT wernmiinsoo integratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT wernmiinsoo integratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT lienghsiling integratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT lienghsiling integratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT robertndoughty integratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT hyungwonchoi integratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT markusrwenk integratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT markusrwenk integratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT amarkrichards integratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT amarkrichards integratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT amarkrichards integratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT markychan integratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes AT markychan integratedsignatureofextracellularmatrixproteinsandadiastolicfunctionimagingparameterpredictspostmilongtermoutcomes |