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.