Precision prognostics for cardiovascular disease in Type 2 diabetes: a systematic review and meta-analysis

Abrar Ahmad; Lee Ling Lim; Mario Luca Morieri; Claudia Ha ting Tam; Feifei Cheng; Tinashe Chikowore; Monika Dudenhöffer-Pfeifer; Hugo Fitipaldi; Chuiguo Huang; Sarah Kanbour; Sudipa Sarkar; Robert Wilhelm Koivula; Ayesha A. Motala; Sok Cin Tye; Gechang Yu; Yingchai Zhang; Michele Provenzano; Diana Sherifali; Russell de Souza; Deirdre K. Tobias; ADA/EASD PMDI; Maria F. Gomez; Ronald C.W. Ma; Nestoras Mathioudakis

doi:10.1038/s43856-023-00429-z

Precision prognostics for cardiovascular disease in Type 2 diabetes: a systematic review and meta-analysis

Abrar Ahmad, Lee Ling Lim, Mario Luca Morieri, Claudia Ha ting Tam, Feifei Cheng, Tinashe Chikowore, Monika Dudenhöffer-Pfeifer, Hugo Fitipaldi, Chuiguo Huang, Sarah Kanbour, Sudipa Sarkar, Robert Wilhelm Koivula, Ayesha A. Motala, Sok Cin Tye, Gechang Yu, Yingchai Zhang, Michele Provenzano, Diana Sherifali, Russell de Souza, Deirdre K. TobiasADA/EASD PMDI, Maria F. Gomez, Ronald C.W. Ma, Nestoras Mathioudakis

Research output: Contribution to journal › Article › Research › peer-review

15 Citations (Scopus)

Abstract

Background: Precision medicine has the potential to improve cardiovascular disease (CVD) risk prediction in individuals with Type 2 diabetes (T2D). Methods: We conducted a systematic review and meta-analysis of longitudinal studies to identify potentially novel prognostic factors that may improve CVD risk prediction in T2D. Out of 9380 studies identified, 416 studies met inclusion criteria. Outcomes were reported for 321 biomarker studies, 48 genetic marker studies, and 47 risk score/model studies. Results: Out of all evaluated biomarkers, only 13 showed improvement in prediction performance. Results of pooled meta-analyses, non-pooled analyses, and assessments of improvement in prediction performance and risk of bias, yielded the highest predictive utility for N-terminal pro b-type natriuretic peptide (NT-proBNP) (high-evidence), troponin-T (TnT) (moderate-evidence), triglyceride-glucose (TyG) index (moderate-evidence), Genetic Risk Score for Coronary Heart Disease (GRS-CHD) (moderate-evidence); moderate predictive utility for coronary computed tomography angiography (low-evidence), single-photon emission computed tomography (low-evidence), pulse wave velocity (moderate-evidence); and low predictive utility for C-reactive protein (moderate-evidence), coronary artery calcium score (low-evidence), galectin-3 (low-evidence), troponin-I (low-evidence), carotid plaque (low-evidence), and growth differentiation factor-15 (low-evidence). Risk scores showed modest discrimination, with lower performance in populations different from the original development cohort. Conclusions: Despite high interest in this topic, very few studies conducted rigorous analyses to demonstrate incremental predictive utility beyond established CVD risk factors for T2D. The most promising markers identified were NT-proBNP, TnT, TyG and GRS-CHD, with the highest strength of evidence for NT-proBNP. Further research is needed to determine their clinical utility in risk stratification and management of CVD in T2D.

Original language	English
Article number	11
Number of pages	28
Journal	Communications Medicine
Volume	4
Issue number	1
DOIs	https://doi.org/10.1038/s43856-023-00429-z
Publication status	Published - 22 Jan 2024

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Ahmad, A., Lim, L. L., Morieri, M. L., Tam, C. H. T., Cheng, F., Chikowore, T., Dudenhöffer-Pfeifer, M., Fitipaldi, H., Huang, C., Kanbour, S., Sarkar, S., Koivula, R. W., Motala, A. A., Tye, S. C., Yu, G., Zhang, Y., Provenzano, M., Sherifali, D., de Souza, R., ... Mathioudakis, N. (2024). Precision prognostics for cardiovascular disease in Type 2 diabetes: a systematic review and meta-analysis. Communications Medicine, 4(1), Article 11. https://doi.org/10.1038/s43856-023-00429-z

@article{3efe99d453904b69b689ffa52fa404a7,

title = "Precision prognostics for cardiovascular disease in Type 2 diabetes: a systematic review and meta-analysis",

abstract = "Background: Precision medicine has the potential to improve cardiovascular disease (CVD) risk prediction in individuals with Type 2 diabetes (T2D). Methods: We conducted a systematic review and meta-analysis of longitudinal studies to identify potentially novel prognostic factors that may improve CVD risk prediction in T2D. Out of 9380 studies identified, 416 studies met inclusion criteria. Outcomes were reported for 321 biomarker studies, 48 genetic marker studies, and 47 risk score/model studies. Results: Out of all evaluated biomarkers, only 13 showed improvement in prediction performance. Results of pooled meta-analyses, non-pooled analyses, and assessments of improvement in prediction performance and risk of bias, yielded the highest predictive utility for N-terminal pro b-type natriuretic peptide (NT-proBNP) (high-evidence), troponin-T (TnT) (moderate-evidence), triglyceride-glucose (TyG) index (moderate-evidence), Genetic Risk Score for Coronary Heart Disease (GRS-CHD) (moderate-evidence); moderate predictive utility for coronary computed tomography angiography (low-evidence), single-photon emission computed tomography (low-evidence), pulse wave velocity (moderate-evidence); and low predictive utility for C-reactive protein (moderate-evidence), coronary artery calcium score (low-evidence), galectin-3 (low-evidence), troponin-I (low-evidence), carotid plaque (low-evidence), and growth differentiation factor-15 (low-evidence). Risk scores showed modest discrimination, with lower performance in populations different from the original development cohort. Conclusions: Despite high interest in this topic, very few studies conducted rigorous analyses to demonstrate incremental predictive utility beyond established CVD risk factors for T2D. The most promising markers identified were NT-proBNP, TnT, TyG and GRS-CHD, with the highest strength of evidence for NT-proBNP. Further research is needed to determine their clinical utility in risk stratification and management of CVD in T2D.",

author = "Abrar Ahmad and Lim, {Lee Ling} and Morieri, {Mario Luca} and Tam, {Claudia Ha ting} and Feifei Cheng and Tinashe Chikowore and Monika Dudenh{\"o}ffer-Pfeifer and Hugo Fitipaldi and Chuiguo Huang and Sarah Kanbour and Sudipa Sarkar and Koivula, {Robert Wilhelm} and Motala, {Ayesha A.} and Tye, {Sok Cin} and Gechang Yu and Yingchai Zhang and Michele Provenzano and Diana Sherifali and {de Souza}, Russell and Tobias, {Deirdre K.} and Franks, {Paul W.} and Rich, {Stephen S.} and Robert Wagner and Tina Vilsb{\o}ll and Vesco, {Kimberly K.} and Udler, {Miriam S.} and Tiinamaija Tuomi and Arianne Sweeting and Sims, {Emily K.} and Sherr, {Jennifer L.} and Semple, {Robert K.} and Reynolds, {Rebecca M.} and Redondo, {Maria J.} and Redman, {Leanne M.} and Pratley, {Richard E.} and Rodica Pop-Busui and Pollin, {Toni I.} and Wei Perng and Pearson, {Ewan R.} and Ozanne, {Susan E.} and Owen, {Katharine R.} and Richard Oram and Rinki Murphy and Viswanathan Mohan and Shivani Misra and Meigs, {James B.} and Nestoras Mathioudakis and Chantal Mathieu and Loos, {Ruth J.F.} and Lim, {Siew S.} and Laffel, {Lori M.} and Kwak, {Soo Heon} and Josefson, {Jami L.} and Hood, {Korey K.} and Hivert, {Marie France} and Hirsch, {Irl B.} and Hattersley, {Andrew T.} and Kurt Griffin and Greeley, {Siri Atma W.} and Gottlieb, {Peter A.} and Gloyn, {Anna L.} and Florez, {Jose C.} and Dennis, {John M.} and Tina Costacou and Kristen Boyle and Billings, {Liana K.} and Brown, {Rebecca J.} and Philipson, {Louis H.} and Nolan, {John J.} and Eckel, {Robert H.} and Emily Mixter and Mekonnen, {Eskedar Getie} and Chandra Gruber and Fawcett, {Andrea J.} and {de Souza}, Russell and Sungyoung Auh and Yeyi Zhu and Cuilin Zhang and C{\'e}cile Saint-Martin and Hugo Pomares-Millan and Nj{\o}lstad, {P{\aa}l Rasmus} and Mariam Nakabuye and Janne Molnes and Andrew McGovern and Maloney, {Kristin A.} and Flanagan, {Sarah E.} and {de Franco}, Elisa and Ingvild Aukrust and Michel Polak and Jacques Beltrand and Zhou, {Shao J.} and White, {Sara L.} and Wesley Hannah and Wentworth, {John M.} and Camille Vatier and {Van der Schueren}, Bart and Marzhan Urazbayeva and Ukke, {Gebresilasea Gendisha} and Rachael Taylor and Julie St{\o}y and Norbert Stefan and Steck, {Andrea K.} and Nele Steenackers and Stanislawski, {Maggie A.} and Cate Speake and Sheu, {Wayne Huey Herng} and Elizabeth Selvin and Scholtens, {Denise M.} and Monaco, {Gabriela S.F.} and Vanessa Santhakumar and Zeb Saeed and Mathias Ried-Larsen and Debashree Ray and Rashmi Jain and Alejandra Quinteros and Powe, {Camille E.} and Petrie, {John R.} and Dianna Perez and Sofia Pazmino and Maleesa Pathirana and Pankow, {James S.} and Suna Onengut-Gumuscu and Morton, {Robert W.} and Lowe, {William L.} and Long, {S. Alice} and Kai Liu and Libman, {Ingrid M.} and Leung, {Gloria K.W.} and Aaron Leong and Koivula, {Robert W.} and Jones, {Angus G.} and Johnson, {Randi K.} and Benjamin Hoag and Ismail, {Heba M.} and Arianna Harris-Kawano and Torben Hansen and Nahal Habibi and Marta Guasch-Ferr{\'e} and Grieger, {Jessica A.} and Goodarzi, {Mark O.} and Gitelman, {Stephen E.} and Fitzpatrick, {Stephanie L.} and Fern{\'a}ndez-Balsells, {Mar{\'i}a Merc{\`e}} and Carmella Evans-Molina and DiMeglio, {Linda A.} and Dickens, {Laura T.} and Deutsch, {Aaron J.} and Dawed, {Adem Y.} and Dana Dabelea and Christoffer Clemmensen and Chivers, {Sian C.} and Mingling Chen and Bonham, {Maxine P.} and Andersen, {Mette K.} and Chlo{\'e} Amouyal and Katherine Young and Yamamoto, {Jennifer M.} and Wong, {Jessie J.} and Wang, {Caroline C.} and Wallace, {Amelia S.} and Mustafa Tosur and Thuesen, {Anne Cathrine B.} and Takele, {Wubet Worku} and Pernille Svalastoga and Magdalena Sevilla-Gonzalez and Zhila Semnani-Azad and Martin Sch{\"o}n and Rooney, {Mary R.} and Sridharan Raghavan and Katsiaryna Prystupa and Pilla, {Scott J.} and Patel, {Kashyap Amratlal} and Bige Ozkan and Naylor, {Rochelle N.} and Jasper Most and Miller, {Rachel G.} and Mclennan, {Niamh Maire} and Robert Massey and M{\"a}nnist{\"o}, {Jonna M.E.} and Lim, {Lee Ling} and Kreienkamp, {Raymond J.} and Kettunen, {Jarno L.T.} and Kahkoska, {Anna R.} and Jacobsen, {Laura M.} and Ikle, {Jennifer M.} and Alice Hughes and Eram Haider and Romy Gaillard and V{\'e}ronique Gingras and Pieter Gillard and Francis, {Ellen C.} and Felton, {Jamie L.} and Daisy Duan and Cromer, {Sara J.} and Rosa Corcoy and Kevin Colclough and Clark, {Amy L.} and Dhanasekaran Bodhini and Benham, {Jamie L.} and Catherine Aiken and Jordi Merino and Tobias, {Deirdre K.} and {ADA/EASD PMDI} and Gomez, {Maria F.} and Ma, {Ronald C.W.} and Nestoras Mathioudakis",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = jan,

day = "22",

doi = "10.1038/s43856-023-00429-z",

language = "English",

volume = "4",

journal = "Communications Medicine",

issn = "2730-664X",

publisher = "Nature Publishing Group",

number = "1",

}

Ahmad, A, Lim, LL, Morieri, ML, Tam, CHT, Cheng, F, Chikowore, T, Dudenhöffer-Pfeifer, M, Fitipaldi, H, Huang, C, Kanbour, S, Sarkar, S, Koivula, RW, Motala, AA, Tye, SC, Yu, G, Zhang, Y, Provenzano, M, Sherifali, D, de Souza, R, Tobias, DK, ADA/EASD PMDI, Gomez, MF, Ma, RCW & Mathioudakis, N 2024, 'Precision prognostics for cardiovascular disease in Type 2 diabetes: a systematic review and meta-analysis', Communications Medicine, vol. 4, no. 1, 11. https://doi.org/10.1038/s43856-023-00429-z

TY - JOUR

T1 - Precision prognostics for cardiovascular disease in Type 2 diabetes

T2 - a systematic review and meta-analysis

AU - Ahmad, Abrar

AU - Lim, Lee Ling

AU - Morieri, Mario Luca

AU - Tam, Claudia Ha ting

AU - Cheng, Feifei

AU - Chikowore, Tinashe

AU - Dudenhöffer-Pfeifer, Monika

AU - Fitipaldi, Hugo

AU - Huang, Chuiguo

AU - Kanbour, Sarah

AU - Sarkar, Sudipa

AU - Koivula, Robert Wilhelm

AU - Motala, Ayesha A.

AU - Tye, Sok Cin

AU - Yu, Gechang

AU - Zhang, Yingchai

AU - Provenzano, Michele

AU - Sherifali, Diana

AU - de Souza, Russell

AU - Tobias, Deirdre K.

AU - Franks, Paul W.

AU - Rich, Stephen S.

AU - Wagner, Robert

AU - Vilsbøll, Tina

AU - Vesco, Kimberly K.

AU - Udler, Miriam S.

AU - Tuomi, Tiinamaija

AU - Sweeting, Arianne

AU - Sims, Emily K.

AU - Sherr, Jennifer L.

AU - Semple, Robert K.

AU - Reynolds, Rebecca M.

AU - Redondo, Maria J.

AU - Redman, Leanne M.

AU - Pratley, Richard E.

AU - Pop-Busui, Rodica

AU - Pollin, Toni I.

AU - Perng, Wei

AU - Pearson, Ewan R.

AU - Ozanne, Susan E.

AU - Owen, Katharine R.

AU - Oram, Richard

AU - Murphy, Rinki

AU - Mohan, Viswanathan

AU - Misra, Shivani

AU - Meigs, James B.

AU - Mathioudakis, Nestoras

AU - Mathieu, Chantal

AU - Loos, Ruth J.F.

AU - Lim, Siew S.

AU - Laffel, Lori M.

AU - Kwak, Soo Heon

AU - Josefson, Jami L.

AU - Hood, Korey K.

AU - Hivert, Marie France

AU - Hirsch, Irl B.

AU - Hattersley, Andrew T.

AU - Griffin, Kurt

AU - Greeley, Siri Atma W.

AU - Gottlieb, Peter A.

AU - Gloyn, Anna L.

AU - Florez, Jose C.

AU - Dennis, John M.

AU - Costacou, Tina

AU - Boyle, Kristen

AU - Billings, Liana K.

AU - Brown, Rebecca J.

AU - Philipson, Louis H.

AU - Nolan, John J.

AU - Eckel, Robert H.

AU - Mixter, Emily

AU - Mekonnen, Eskedar Getie

AU - Gruber, Chandra

AU - Fawcett, Andrea J.

AU - de Souza, Russell

AU - Auh, Sungyoung

AU - Zhu, Yeyi

AU - Zhang, Cuilin

AU - Saint-Martin, Cécile

AU - Pomares-Millan, Hugo

AU - Njølstad, Pål Rasmus

AU - Nakabuye, Mariam

AU - Molnes, Janne

AU - McGovern, Andrew

AU - Maloney, Kristin A.

AU - Flanagan, Sarah E.

AU - de Franco, Elisa

AU - Aukrust, Ingvild

AU - Polak, Michel

AU - Beltrand, Jacques

AU - Zhou, Shao J.

AU - White, Sara L.

AU - Hannah, Wesley

AU - Wentworth, John M.

AU - Vatier, Camille

AU - Van der Schueren, Bart

AU - Urazbayeva, Marzhan

AU - Ukke, Gebresilasea Gendisha

AU - Taylor, Rachael

AU - Støy, Julie

AU - Stefan, Norbert

AU - Steck, Andrea K.

AU - Steenackers, Nele

AU - Stanislawski, Maggie A.

AU - Speake, Cate

AU - Sheu, Wayne Huey Herng

AU - Selvin, Elizabeth

AU - Scholtens, Denise M.

AU - Monaco, Gabriela S.F.

AU - Santhakumar, Vanessa

AU - Saeed, Zeb

AU - Ried-Larsen, Mathias

AU - Ray, Debashree

AU - Jain, Rashmi

AU - Quinteros, Alejandra

AU - Powe, Camille E.

AU - Petrie, John R.

AU - Perez, Dianna

AU - Pazmino, Sofia

AU - Pathirana, Maleesa

AU - Pankow, James S.

AU - Onengut-Gumuscu, Suna

AU - Morton, Robert W.

AU - Lowe, William L.

AU - Long, S. Alice

AU - Liu, Kai

AU - Libman, Ingrid M.

AU - Leung, Gloria K.W.

AU - Leong, Aaron

AU - Koivula, Robert W.

AU - Jones, Angus G.

AU - Johnson, Randi K.

AU - Hoag, Benjamin

AU - Ismail, Heba M.

AU - Harris-Kawano, Arianna

AU - Hansen, Torben

AU - Habibi, Nahal

AU - Guasch-Ferré, Marta

AU - Grieger, Jessica A.

AU - Goodarzi, Mark O.

AU - Gitelman, Stephen E.

AU - Fitzpatrick, Stephanie L.

AU - Fernández-Balsells, María Mercè

AU - Evans-Molina, Carmella

AU - DiMeglio, Linda A.

AU - Dickens, Laura T.

AU - Deutsch, Aaron J.

AU - Dawed, Adem Y.

AU - Dabelea, Dana

AU - Clemmensen, Christoffer

AU - Chivers, Sian C.

AU - Chen, Mingling

AU - Bonham, Maxine P.

AU - Andersen, Mette K.

AU - Amouyal, Chloé

AU - Young, Katherine

AU - Yamamoto, Jennifer M.

AU - Wong, Jessie J.

AU - Wang, Caroline C.

AU - Wallace, Amelia S.

AU - Tosur, Mustafa

AU - Thuesen, Anne Cathrine B.

AU - Takele, Wubet Worku

AU - Svalastoga, Pernille

AU - Sevilla-Gonzalez, Magdalena

AU - Semnani-Azad, Zhila

AU - Schön, Martin

AU - Rooney, Mary R.

AU - Raghavan, Sridharan

AU - Prystupa, Katsiaryna

AU - Pilla, Scott J.

AU - Patel, Kashyap Amratlal

AU - Ozkan, Bige

AU - Naylor, Rochelle N.

AU - Most, Jasper

AU - Miller, Rachel G.

AU - Mclennan, Niamh Maire

AU - Massey, Robert

AU - Männistö, Jonna M.E.

AU - Lim, Lee Ling

AU - Kreienkamp, Raymond J.

AU - Kettunen, Jarno L.T.

AU - Kahkoska, Anna R.

AU - Jacobsen, Laura M.

AU - Ikle, Jennifer M.

AU - Hughes, Alice

AU - Haider, Eram

AU - Gaillard, Romy

AU - Gingras, Véronique

AU - Gillard, Pieter

AU - Francis, Ellen C.

AU - Felton, Jamie L.

AU - Duan, Daisy

AU - Cromer, Sara J.

AU - Corcoy, Rosa

AU - Colclough, Kevin

AU - Clark, Amy L.

AU - Bodhini, Dhanasekaran

AU - Benham, Jamie L.

AU - Aiken, Catherine

AU - Merino, Jordi

AU - Tobias, Deirdre K.

AU - ADA/EASD PMDI

AU - Gomez, Maria F.

AU - Ma, Ronald C.W.

AU - Mathioudakis, Nestoras

PY - 2024/1/22

Y1 - 2024/1/22

N2 - Background: Precision medicine has the potential to improve cardiovascular disease (CVD) risk prediction in individuals with Type 2 diabetes (T2D). Methods: We conducted a systematic review and meta-analysis of longitudinal studies to identify potentially novel prognostic factors that may improve CVD risk prediction in T2D. Out of 9380 studies identified, 416 studies met inclusion criteria. Outcomes were reported for 321 biomarker studies, 48 genetic marker studies, and 47 risk score/model studies. Results: Out of all evaluated biomarkers, only 13 showed improvement in prediction performance. Results of pooled meta-analyses, non-pooled analyses, and assessments of improvement in prediction performance and risk of bias, yielded the highest predictive utility for N-terminal pro b-type natriuretic peptide (NT-proBNP) (high-evidence), troponin-T (TnT) (moderate-evidence), triglyceride-glucose (TyG) index (moderate-evidence), Genetic Risk Score for Coronary Heart Disease (GRS-CHD) (moderate-evidence); moderate predictive utility for coronary computed tomography angiography (low-evidence), single-photon emission computed tomography (low-evidence), pulse wave velocity (moderate-evidence); and low predictive utility for C-reactive protein (moderate-evidence), coronary artery calcium score (low-evidence), galectin-3 (low-evidence), troponin-I (low-evidence), carotid plaque (low-evidence), and growth differentiation factor-15 (low-evidence). Risk scores showed modest discrimination, with lower performance in populations different from the original development cohort. Conclusions: Despite high interest in this topic, very few studies conducted rigorous analyses to demonstrate incremental predictive utility beyond established CVD risk factors for T2D. The most promising markers identified were NT-proBNP, TnT, TyG and GRS-CHD, with the highest strength of evidence for NT-proBNP. Further research is needed to determine their clinical utility in risk stratification and management of CVD in T2D.

AB - Background: Precision medicine has the potential to improve cardiovascular disease (CVD) risk prediction in individuals with Type 2 diabetes (T2D). Methods: We conducted a systematic review and meta-analysis of longitudinal studies to identify potentially novel prognostic factors that may improve CVD risk prediction in T2D. Out of 9380 studies identified, 416 studies met inclusion criteria. Outcomes were reported for 321 biomarker studies, 48 genetic marker studies, and 47 risk score/model studies. Results: Out of all evaluated biomarkers, only 13 showed improvement in prediction performance. Results of pooled meta-analyses, non-pooled analyses, and assessments of improvement in prediction performance and risk of bias, yielded the highest predictive utility for N-terminal pro b-type natriuretic peptide (NT-proBNP) (high-evidence), troponin-T (TnT) (moderate-evidence), triglyceride-glucose (TyG) index (moderate-evidence), Genetic Risk Score for Coronary Heart Disease (GRS-CHD) (moderate-evidence); moderate predictive utility for coronary computed tomography angiography (low-evidence), single-photon emission computed tomography (low-evidence), pulse wave velocity (moderate-evidence); and low predictive utility for C-reactive protein (moderate-evidence), coronary artery calcium score (low-evidence), galectin-3 (low-evidence), troponin-I (low-evidence), carotid plaque (low-evidence), and growth differentiation factor-15 (low-evidence). Risk scores showed modest discrimination, with lower performance in populations different from the original development cohort. Conclusions: Despite high interest in this topic, very few studies conducted rigorous analyses to demonstrate incremental predictive utility beyond established CVD risk factors for T2D. The most promising markers identified were NT-proBNP, TnT, TyG and GRS-CHD, with the highest strength of evidence for NT-proBNP. Further research is needed to determine their clinical utility in risk stratification and management of CVD in T2D.

UR - http://www.scopus.com/inward/record.url?scp=85198222649&partnerID=8YFLogxK

U2 - 10.1038/s43856-023-00429-z

DO - 10.1038/s43856-023-00429-z

M3 - Article

C2 - 38253823

AN - SCOPUS:85198222649

SN - 2730-664X

VL - 4

JO - Communications Medicine

JF - Communications Medicine

IS - 1

M1 - 11

ER -

Precision prognostics for cardiovascular disease in Type 2 diabetes: a systematic review and meta-analysis

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