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Observational Study
. 2024 Jan 16;13(2):e031646.
doi: 10.1161/JAHA.123.031646. Epub 2024 Jan 12.

Acute Coronary Syndrome Subphenotypes Based on Repeated Biomarker Measurements in Relation to Long-Term Mortality Risk

Marie de Bakker  1 , Niels T B Scholte  1 , Rohit M Oemrawsingh  2 , Victor A Umans  3 , Bas Kietselaer  4 , Carl Schotborgh  5 , Eelko Ronner  6 , Timo Lenderink  7 , Ismail Aksoy  8 , Pim van der Harst  9 , Folkert W Asselbergs  10   11 , Arthur Maas  12 , Anton J Oude Ophuis  13 , Boudewijn Krenning  1   14 , Robbert J de Winter  10 , S Hong Kie The  15 , Alexander J Wardeh  16 , Walter Hermans  17 , G Etienne Cramer  18 , Ron H van Schaik  19 , Yolanda B de Rijke  19 , K Martijn Akkerhuis  1 , Isabella Kardys  1 , Eric Boersma  1 ; BIOMArCS Investigators †
Collaborators, Affiliations
Observational Study

Acute Coronary Syndrome Subphenotypes Based on Repeated Biomarker Measurements in Relation to Long-Term Mortality Risk

Marie de Bakker et al. J Am Heart Assoc. .

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-frequency 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-term 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.

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Figures

Figure 1
Figure 1. Clusters' biomarker trajectories during the first year following index ACS.
Biomarker trajectories of repeated measurements‐based clusters during the first year following the index ACS. The solid lines depict the average biomarker evolutions in each cluster separately. The dashed lines represent the 95% CI. Samples taken within 30 days after index ACS or repeat ACS are excluded from analyses. ACS indicates acute coronary syndrome; GDF‐15, growth differentiation factor 15; hs‐CRP, high‐sensitivity C‐reactive protein; hs‐cTnT, high‐sensitivity cardiac troponin T; and NT‐proBNP, N‐terminal pro‐B‐type natriuretic peptide.
Figure 2
Figure 2. Association between clusters based on repeated biomarker measurements and long‐term all‐cause death.
ACS indicates acute coronary syndrome.
Figure 3
Figure 3. Reclassification diagram.
The low biomarker cluster based on single 1‐year biomarker estimates coincides mostly with the combined clusters 1 and 2 on the basis of repeated biomarker measurements. The high biomarker cluster based on single 1‐year biomarker coincides mostly with cluster 3 on the basis of repeated biomarker measurements.
See this image and copyright information in PMC

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