Boersma, Eric

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.

Abstract Aims Evidence regarding the role of serial measurements of biomarkers for risk assessment in post-acute coronary syndrome (ACS) patients is limited. The aim was to explore the prognostic value of four, serially measured biomarkers in a large, real-world cohort of post-ACS patients. Methods and results BIOMArCS is a prospective, multi-centre, observational study in 844 post-ACS patients in whom 12 218 blood samples (median 17 per patient) were obtained during 1-year follow-up. The longitudinal patterns of high-sensitivity cardiac troponin T (hs-cTnT), N-terminal-pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and growth differentiation factor 15 (GDF-15) were analysed in relation to the primary endpoint (PE) of cardiovascular mortality and recurrent ACS using multivariable joint models. Median age was 63 years, 78% were men and the PE was reached by 45 patients. The average biomarker levels were systematically higher in PE compared with PE-free patients. After adjustment for 6-month post-discharge Global Registry of Acute Coronary Events score, 1 standard deviation increase in log[hs-cTnT] was associated with a 61% increased risk of the PE [hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.02–2.44, P = 0.045], while for log[GDF-15] this was 81% (HR 1.81, 95% CI 1.28–2.70, P = 0.001). These associations remained significant after multivariable adjustment, while NT-proBNP and hs-CRP were not. Furthermore, GDF-15 level showed an increasing trend prior to the PE (Structured Graphical Abstract). Conclusion Longitudinally measured hs-cTnT and GDF-15 concentrations provide prognostic value in the risk assessment of clinically stabilized patients post-ACS. Clinical Trial Registration The Netherlands Trial Register. Currently available at URL https://trialsearch.who.int/; Unique Identifiers: NTR1698 and NTR1106.

Periprocedural bleeding is one of the most frequent complications of percutaneours coronary interventions. We assessed the relation between blood transfusion and all-cause mortality or incident cardiovascular events (death, MI, stroke) among 6103 patients of the Evaluation of Oral Xemilofiban in Controlling Thrombotic Events (EXCITE)-trial. Subjects were followed for 7 months after enrollment for the occurrence of events. Multivariate Cox-regression analysis evaluated the independent association of blood transfusion with each outcome adjusted for age, gender, race, diabetes mellitus, hypertension, hypercholesterolemia, history of MI, PCI, CABG, heart failure, LVEF<30%, use of beta-blockers, statins, ACE-inhibitors, platelet inhibitors and allocation to treatment with xemolifiban. In addition, propensity score analyses were performed (ROC 0.80). Mean age was 59.2 years, 21.7% were female, and 18.9% had diabetes mellitus. Of the169 patients who received blood transfusion, 14 (8.3%) died and 42 (24.9%) experienced a CVD event. Of the 5934 patients without transfusion, 65 (1.1%) died (p-value: <0.001) and 555 (9,4%) experienced a CVD event (p-value: <0.001) In multivariate analysis, blood transfusion was associated with a 5.3 fold increased risk of mortality (HR 5.3; 95% CI 2.8 –10.2), and a 2.5 fold increased risk of incident CVD (HR 2.5; 95% CI 1.7–3.4.) Noteworthy, patients who were US citizens had a higher transfusion rate then non-US citizens (OR 1.45, 95%CI 1.02–2.06) The need of blood transfusion is a strong and independent predictor of all-cause mortality and incident CVD events among patients undergoing PCI.