Biomarker Prognostic Cocktail in Acute Coronary Syndrome

Acute coronary syndrome (ACS) results in a high rate of short-term death. Estimates of short-term death the rate shortly after an ACS event range between 1.7% (unstable angina) to as high as 9.8% (ST-segment myocardial infarction).¹ However, long-term mortality data has proven to be more difficult to obtain due to selection and information bias.²  

A recent study published in Heart, Lung and Circulation from the New Zealand (NZ) Acute Coronary Syndrome Audit assessed 12-year mortality from an ACS event.²  They reviewed 721 patients with a discharge diagnosis of ACS from 2002.  They matched the cohort to a NZ national mortality database using each patient’s unique national identity number.  The median follow-up was 12.7 years.  Overall mortality was 52% with STEMI at 58%, NSTEMI at 61%, and UA at 42% of patients.  Males had a 29% increase in mortality compared to females (HR: 1.29 95% CI: 1.04-1.61). 

The data from NZ suggests the need for prognostic markers that provide clinicians with risk assessment for cause-specific mortality in ACS.  The platelet inhibition and patient outcomes (PLATO) trial was interrogated to determine death from myocardial infarction, heart failure, sudden cardiac death/arrhythmia, bleeding, procedures, other vascular causes, and nonvascular causes as well as all-cause death. At baseline, cystatin-C, growth differentiation factor-15 (GDF-15), high-sensitivity C-reactive protein (hs-CRP), high-sensitivity troponin I and T, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were determined.³  For all-cause mortality, NT-proBNP and GDF-15 were the strongest predictors (HR: 2.96 95% CI: [2.33-3.76]) and (2.65: [2.17-3.24]), respectively.  For heart failure death, NT-proBNP was associated with an 8-fold increase in death and cystatin-C, hs-CRP, and GDF-15 with a 3-fold increase.  Sudden death/arrhythmia was associated with a 4-fold increase from NT-proBNP and GDF-15 with a doubling of risk.  Finally, for vascular and nonvascular death GDF-15 had the strongest association and was associated with death due to major bleeding (HR: 4.91 [95% CI: 1.39-17.43]).

These results show that different biomarkers are associated with separate outcomes post-ACS.  A cocktail of cystatin-C, GDF-15, and NT-proBNP appear to be the most predictive of all-cause, heart failure and sudden death.  GDF-15 is a predictor of bleeding in patients who are administered dual antiplatelet therapy.⁴ Renal, cardiac contractile, and inflammation (aging) appear to be the most predictive biologic mechanisms underlying a poor prognosis post-ACS.

Table 1: Biomarkers with Biologic Definitions

Mark A. Munger, PharmD, FCCP, FACC, is a professor of pharmacotherapy and adjunct professor of internal medicine, at the University of Utah, where he also serves as the associate dean of Academic Affairs for the College of Pharmacy.  

References:

1. Brieger DB, Chew DPB, Refern J, Ellis C, Briffa TG, Howell TE, et al. Survival after an acute coronary syndrome: 18-month outcomes from the Australian and New Zealand SAPSSHOT ACS Study. MJA 2015;9:368 31-368.e9.
2. Ellis CJ, Gamble GD, Williams MJA, et al. For the regional Cardiac Society NZ ACS Audit Group. Heart, Lung and Circulation 2019;28:245-56.
3. Lindholm D, James SK, Gabrysch K, et al. Association of multiple biomarkers with risk of all-cause and cause-specific mortality after acute coronary syndromes. A secondary analysis of the PLATO Biomarker Study. JAMA Cardiology 2018;3(12):1160-6.
4. Hagstrõm E, James SK, Bertilson M, et al. Growth differentiation factor-15 level predicts major bleeding and cardiovascular events in patients with acute coronary syndromes: results from the PLATO study, Eur Heart J 2016;37(6):1324-33.
5. Cystatin-C Definition: https://www.medicinenet.com/script/main/art.asp?articlekey=39781 Accessed 12/2019
6. Growth Differentiation Factor Defintion: https://www.sciencedirect.com/topics/medicine-and-dentistry/growth-differentiation-factor-15 Accessed 12/2019
7. C-Reactive Protein Definition:   https://www.medicinenet.com/script/main/art.asp?articlekey=101379  Accessed 12/2019
8. Bay M, Kirk V, Parner, J, et al. NT-proBNP: A new diagnostic screening tool to differentiate between patients with normal an reduced left ventricular systolic function. Heart 2003;89:150-4.
9. Troponin I and T Definition: https://labtestsonline.org/tests/troponin Accessed 12/2019.