Placental Growth Factor and B-Type Natriuretic Peptide as Independent Predictors of Risk from a Multibiomarker Panel in Suspected Acute Coronary Syndrome (Acute Risk and Related Outcomes Assessed With Cardiac Biomarkers [ARROW]) Study

Abstract

Most patients presenting to the emergency department with possible cardiac symptoms have low cardiac troponin (cTn) concentrations. A combination of biomarkers that improves risk stratification in patients at very low risk for major adverse cardiovascular events (MACEs) would be beneficial. In this multicenter prospective cohort study, specimens from 598 subjects presenting to 5 emergency departments with suspected acute coronary syndromes were collected on arrival and serially for traditional and novel biomarkers. Subjects were evaluated for MACEs, defined as death, myocardial infarction, or revascularization at 30 and 365 days. Classification and regression tree analysis assessed biomarker and clinical factors associated with MACEs. The 1-year rate of MACE was 10.5% (47 of 449). Rates of death, myocardial infarction, and revascularization were 4.2%, 1.6%, and 4.7%, respectively. The combination of B-type natriuretic peptide (BNP), placental growth factor (PlGF), and estimated glomerular filtration rate (eGFR) was the most accurate predictor of MACEs compared to any other biomarker or clinical factors including cTnI. If BNP was ≤ 65 ng/L and PlGF was ≤ 19.5 ng/L, the negative predictive value for 1-year MACEs was 99.1%. Conversely, BNP >150 ng/L and eGFR ≤ 68 ml/min/1.73 m(2) predicted a very high (36.5%) MACE rate. Prognostic values of BNP and PlGF were incremental (none increased, 2 of 212, 0.9%; only PlGF increased, 30 of 170, 17.6%; only BNP increased, 33 of 153, 21.6%; BNP and PlGF increased, 18 of 86, 20.9%). Considering only initial emergency department samples, 97% and 96% of patients with normal PlGF, BNP, and cTnI levels were event-free at 30 and 365 days, respectively. In conclusion, the combination of BNP, PlGF, and eGFR is the most accurate in risk-stratifying patients with suspected acute coronary syndrome.