Acute coronary syndrome subphenotypes based on repeated biomarker measurements in relation to long-term mortality risk

Marie De Bakker; Niels T.B. Scholte; Rohit M. Oemrawsingh; Victor A. Umans; Bas Kietselaer; Carl Schotborgh; Eelko Ronner; Timo Lenderink; Ismail Aksoy; Pim Van Der Harst; Folkert W. Asselbergs; Arthur Maas; Anton J.Oude Ophuis; Boudewijn Krenning; Robbert J. De Winter; S. Hong Kie The; Alexander J. Wardeh; Walter Hermans; G. Etienne Cramer; Ron H. Van Schaik; Yolanda B. De Rijke; K. Martijn Akkerhuis; Isabella Kardys; Eric Boersma

doi:10.1161/JAHA.123.031646

Acute coronary syndrome subphenotypes based on repeated biomarker measurements in relation to long-term mortality risk

Marie De Bakker, Niels T.B. Scholte, Rohit M. Oemrawsingh, Victor A. Umans, Bas Kietselaer, Carl Schotborgh, Eelko Ronner, Timo Lenderink, Ismail Aksoy, Pim Van Der Harst, Folkert W. Asselbergs, Arthur Maas, Anton J.Oude Ophuis, Boudewijn Krenning, Robbert J. De Winter, S. Hong Kie The, Alexander J. Wardeh, Walter Hermans, G. Etienne Cramer, Ron H. Van SchaikYolanda B. De Rijke, K. Martijn Akkerhuis, Isabella Kardys, Eric Boersma^*,

^*Corresponding author for this work

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

2 Downloads (Pure)

Abstract

BACKGROUND: We aimed to identify patients with subphenotypes of postacute coronary syndrome (ACS) using repeated measurements of high- sensitivity cardiac troponin T, N- terminal pro- B- type natriuretic peptide, high- sensitivity C- reactive protein, and growth differentiation factor 15 in the year after the index admission, and to investigate their association with long- term mortality risk. METHODS AND RESULTS: BIOMArCS (BIOMarker Study to Identify the Acute Risk of a Coronary Syndrome) was an observational study of patients with ACS, who underwent high-f requency blood sampling for 1 year. Biomarkers were measured in a median of 16 repeated samples per individual. Cluster analysis was performed to identify biomarker- based subphenotypes in 723 patients without a repeat ACS in the first year. Patients with a repeat ACS (N=36) were considered a separate cluster. Differences in all- cause death were evaluated using accelerated failure time models (median follow- up, 9.1 years; 141 deaths). Three biomarker- based clusters were identified: Cluster 1 showed low and stable biomarker concentrations, cluster 2 had elevated concentrations that subsequently decreased, and cluster 3 showed persistently elevated concentrations. The temporal biomarker patterns of patients in cluster 3 were similar to those with a repeat ACS during the first year. Clusters 1 and 2 had a similar and favorable long- term mortality risk. Cluster 3 had the highest mortality risk. The adjusted survival time ratio was 0.64 (95% CI, 0.44–0.93; P=0.018) compared with cluster 1, and 0.71 (95% CI, 0.39–1.32; P=0.281) compared with patients with a repeat ACS. CONCLUSIONS: Patients with subphenotypes of post- ACS with different all- cause mortality risks during long-t erm follow- up can be identified on the basis of repeatedly measured cardiovascular biomarkers. Patients with persistently elevated biomarkers have the worst outcomes, regardless of whether they experienced a repeat ACS in the first year.

Original language	English
Article number	e031646
Journal	Journal of the American Heart Association
Volume	13
Issue number	2
DOIs	https://doi.org/10.1161/JAHA.123.031646
Publication status	Published - 16 Jan 2024

Keywords

Acute coronary syndrome
Cardiovascular biomarkers
Death
Phenotypes
Repeated measurements

Access to Document

10.1161/JAHA.123.031646Licence: CC BY-NC-ND

de-bakker-et-al-2024-acute-coronary-syndrome-subphenotypes-based-on-repeated-biomarker-measurements-in-relation-to-longFinal published version, 652 KBLicence: CC BY-NC-ND

Cite this

De Bakker, M., Scholte, N. T. B., Oemrawsingh, R. M., Umans, V. A., Kietselaer, B., Schotborgh, C., Ronner, E., Lenderink, T., Aksoy, I., Van Der Harst, P., Asselbergs, F. W., Maas, A., Ophuis, A. J. O., Krenning, B., De Winter, R. J., Kie The, S. H., Wardeh, A. J., Hermans, W., Cramer, G. E. (2024). Acute coronary syndrome subphenotypes based on repeated biomarker measurements in relation to long-term mortality risk. Journal of the American Heart Association, 13(2), Article e031646. https://doi.org/10.1161/JAHA.123.031646

@article{c6aae1b461204a598714b03765ae8861,

title = "Acute coronary syndrome subphenotypes based on repeated biomarker measurements in relation to long-term mortality risk",

abstract = "BACKGROUND: We aimed to identify patients with subphenotypes of postacute coronary syndrome (ACS) using repeated measurements of high- sensitivity cardiac troponin T, N- terminal pro- B- type natriuretic peptide, high- sensitivity C- reactive protein, and growth differentiation factor 15 in the year after the index admission, and to investigate their association with long- term mortality risk. METHODS AND RESULTS: BIOMArCS (BIOMarker Study to Identify the Acute Risk of a Coronary Syndrome) was an observational study of patients with ACS, who underwent high-f requency blood sampling for 1 year. Biomarkers were measured in a median of 16 repeated samples per individual. Cluster analysis was performed to identify biomarker- based subphenotypes in 723 patients without a repeat ACS in the first year. Patients with a repeat ACS (N=36) were considered a separate cluster. Differences in all- cause death were evaluated using accelerated failure time models (median follow- up, 9.1 years; 141 deaths). Three biomarker- based clusters were identified: Cluster 1 showed low and stable biomarker concentrations, cluster 2 had elevated concentrations that subsequently decreased, and cluster 3 showed persistently elevated concentrations. The temporal biomarker patterns of patients in cluster 3 were similar to those with a repeat ACS during the first year. Clusters 1 and 2 had a similar and favorable long- term mortality risk. Cluster 3 had the highest mortality risk. The adjusted survival time ratio was 0.64 (95% CI, 0.44–0.93; P=0.018) compared with cluster 1, and 0.71 (95% CI, 0.39–1.32; P=0.281) compared with patients with a repeat ACS. CONCLUSIONS: Patients with subphenotypes of post- ACS with different all- cause mortality risks during long-t erm follow- up can be identified on the basis of repeatedly measured cardiovascular biomarkers. Patients with persistently elevated biomarkers have the worst outcomes, regardless of whether they experienced a repeat ACS in the first year.",

keywords = "Acute coronary syndrome, Cardiovascular biomarkers, Death, Phenotypes, Repeated measurements",

author = "{De Bakker}, Marie and Scholte, {Niels T.B.} and Oemrawsingh, {Rohit M.} and Umans, {Victor A.} and Bas Kietselaer and Carl Schotborgh and Eelko Ronner and Timo Lenderink and Ismail Aksoy and {Van Der Harst}, Pim and Asselbergs, {Folkert W.} and Arthur Maas and Ophuis, {Anton J.Oude} and Boudewijn Krenning and {De Winter}, {Robbert J.} and {Kie The}, {S. Hong} and Wardeh, {Alexander J.} and Walter Hermans and Cramer, {G. Etienne} and {Van Schaik}, {Ron H.} and {De Rijke}, {Yolanda B.} and Akkerhuis, {K. Martijn} and Isabella Kardys and Eric Boersma",

year = "2024",

month = jan,

day = "16",

doi = "10.1161/JAHA.123.031646",

language = "English",

volume = "13",

journal = "Journal of the American Heart Association",

issn = "2047-9980",

publisher = "Wiley-Blackwell",

number = "2",

}

De Bakker, M, Scholte, NTB, Oemrawsingh, RM, Umans, VA, Kietselaer, B, Schotborgh, C, Ronner, E, Lenderink, T, Aksoy, I, Van Der Harst, P , Asselbergs, FW, Maas, A, Ophuis, AJO, Krenning, B, De Winter, RJ, Kie The, SH, Wardeh, AJ, Hermans, W, Cramer, GE, Van Schaik, RH, De Rijke, YB, Akkerhuis, KM, Kardys, I, Boersma, E 2024, 'Acute coronary syndrome subphenotypes based on repeated biomarker measurements in relation to long-term mortality risk', Journal of the American Heart Association, vol. 13, no. 2, e031646. https://doi.org/10.1161/JAHA.123.031646

TY - JOUR

T1 - Acute coronary syndrome subphenotypes based on repeated biomarker measurements in relation to long-term mortality risk

AU - De Bakker, Marie

AU - Scholte, Niels T.B.

AU - Oemrawsingh, Rohit M.

AU - Umans, Victor A.

AU - Kietselaer, Bas

AU - Schotborgh, Carl

AU - Ronner, Eelko

AU - Lenderink, Timo

AU - Aksoy, Ismail

AU - Van Der Harst, Pim

AU - Asselbergs, Folkert W.

AU - Maas, Arthur

AU - Ophuis, Anton J.Oude

AU - Krenning, Boudewijn

AU - De Winter, Robbert J.

AU - Kie The, S. Hong

AU - Wardeh, Alexander J.

AU - Hermans, Walter

AU - Cramer, G. Etienne

AU - Van Schaik, Ron H.

AU - De Rijke, Yolanda B.

AU - Akkerhuis, K. Martijn

AU - Kardys, Isabella

AU - Boersma, Eric

PY - 2024/1/16

Y1 - 2024/1/16

N2 - BACKGROUND: We aimed to identify patients with subphenotypes of postacute coronary syndrome (ACS) using repeated measurements of high- sensitivity cardiac troponin T, N- terminal pro- B- type natriuretic peptide, high- sensitivity C- reactive protein, and growth differentiation factor 15 in the year after the index admission, and to investigate their association with long- term mortality risk. METHODS AND RESULTS: BIOMArCS (BIOMarker Study to Identify the Acute Risk of a Coronary Syndrome) was an observational study of patients with ACS, who underwent high-f requency blood sampling for 1 year. Biomarkers were measured in a median of 16 repeated samples per individual. Cluster analysis was performed to identify biomarker- based subphenotypes in 723 patients without a repeat ACS in the first year. Patients with a repeat ACS (N=36) were considered a separate cluster. Differences in all- cause death were evaluated using accelerated failure time models (median follow- up, 9.1 years; 141 deaths). Three biomarker- based clusters were identified: Cluster 1 showed low and stable biomarker concentrations, cluster 2 had elevated concentrations that subsequently decreased, and cluster 3 showed persistently elevated concentrations. The temporal biomarker patterns of patients in cluster 3 were similar to those with a repeat ACS during the first year. Clusters 1 and 2 had a similar and favorable long- term mortality risk. Cluster 3 had the highest mortality risk. The adjusted survival time ratio was 0.64 (95% CI, 0.44–0.93; P=0.018) compared with cluster 1, and 0.71 (95% CI, 0.39–1.32; P=0.281) compared with patients with a repeat ACS. CONCLUSIONS: Patients with subphenotypes of post- ACS with different all- cause mortality risks during long-t erm follow- up can be identified on the basis of repeatedly measured cardiovascular biomarkers. Patients with persistently elevated biomarkers have the worst outcomes, regardless of whether they experienced a repeat ACS in the first year.

AB - BACKGROUND: We aimed to identify patients with subphenotypes of postacute coronary syndrome (ACS) using repeated measurements of high- sensitivity cardiac troponin T, N- terminal pro- B- type natriuretic peptide, high- sensitivity C- reactive protein, and growth differentiation factor 15 in the year after the index admission, and to investigate their association with long- term mortality risk. METHODS AND RESULTS: BIOMArCS (BIOMarker Study to Identify the Acute Risk of a Coronary Syndrome) was an observational study of patients with ACS, who underwent high-f requency blood sampling for 1 year. Biomarkers were measured in a median of 16 repeated samples per individual. Cluster analysis was performed to identify biomarker- based subphenotypes in 723 patients without a repeat ACS in the first year. Patients with a repeat ACS (N=36) were considered a separate cluster. Differences in all- cause death were evaluated using accelerated failure time models (median follow- up, 9.1 years; 141 deaths). Three biomarker- based clusters were identified: Cluster 1 showed low and stable biomarker concentrations, cluster 2 had elevated concentrations that subsequently decreased, and cluster 3 showed persistently elevated concentrations. The temporal biomarker patterns of patients in cluster 3 were similar to those with a repeat ACS during the first year. Clusters 1 and 2 had a similar and favorable long- term mortality risk. Cluster 3 had the highest mortality risk. The adjusted survival time ratio was 0.64 (95% CI, 0.44–0.93; P=0.018) compared with cluster 1, and 0.71 (95% CI, 0.39–1.32; P=0.281) compared with patients with a repeat ACS. CONCLUSIONS: Patients with subphenotypes of post- ACS with different all- cause mortality risks during long-t erm follow- up can be identified on the basis of repeatedly measured cardiovascular biomarkers. Patients with persistently elevated biomarkers have the worst outcomes, regardless of whether they experienced a repeat ACS in the first year.

KW - Acute coronary syndrome

KW - Cardiovascular biomarkers

KW - Death

KW - Phenotypes

KW - Repeated measurements

UR - http://www.scopus.com/inward/record.url?scp=85182594171&partnerID=8YFLogxK

U2 - 10.1161/JAHA.123.031646

DO - 10.1161/JAHA.123.031646

M3 - Article

C2 - 38214281

AN - SCOPUS:85182594171

SN - 2047-9980

VL - 13

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

IS - 2

M1 - e031646

ER -

Acute coronary syndrome subphenotypes based on repeated biomarker measurements in relation to long-term mortality risk

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this