Lipoprotein-associated phospholipase A2 for early risk stratification in patients with suspected acute coronary syndrome: a multi-marker approach: the North Wuerttemberg and Berlin Infarction Study-II (NOBIS-II).

AIMS: Numerous markers have been identified as useful predictors of major adverse cardiac events (MACE) in patients with suspected acute coronary syndrome (ACS). However, only little is known about the relative benefit of the single markers in risk stratification and the best combination for optimising prognostic power. The aim of the present study was to define the role of the emerging cardiovascular risk marker lipoprotein-associated phospholipase A2 (Lp-PLA2) in a multi-marker approach in combination with troponin I (TnI), NT-proBNP, high sensitivity (hs)CRP, and D-dimer in patients with ACS. METHODS AND
RESULTS: A total of 429 consecutive patients (age 60.5+/-14.1 years, 60.6% male) who were admitted to the emergency room with suspected ACS were analysed in the study. Biochemical markers were measured by immunoassay techniques. All patients underwent point-of-care TnI testing and early coronary angiography if appropriate, in accordance with the current guidelines. Classification and regression trees (CART) and logistic regression techniques were employed to determine the relative predictive power of markers for the primary end-point defined as any of the following events within 42 days after admission: death, non-fatal myocardial infarction, unstable AP requiring admission, admission for decompensated heart failure or shock, percutaneous coronary intervention, coronary artery bypass grafting, life threatening arrhythmias or resuscitation. The incidence of the primary end-point was 13.1%, suggesting a mild to moderate risk population. The best overall risk stratification was obtained using NT-proBNP at a cut-off of 5000 pg/mL (incidence of 40% versus 10.3%, relative risk (RR) 3.9 (95% CI 2.4-6.3)). In the remaining lower risk group with an incidence of 10.3%, further separation was performed using TnI (cut-off 0.14 microg/L; RR=3.1 (95% CI 1.7-5.5) 23.2% versus 7.5%) and again NT-proBNP (at a cut-off of 140 ng/L) in patients with negative TnI (RR=3.2 (95% CI 1.3-7.9), 11.7% versus 3.6%). A final significant stratification in patients with moderately elevated NT-proBNP levels was achieved using Lp-PLA2 at a cut-off of 210 microg/L) (17.9% versus 6.9%; RR=2.6 (95% CI 1.1-6.6)). None of the clinical or ECG variables of the TIMI (Thrombolysis In Myocardial Infarction) risk score provided comparable clinically relevant information for risk stratification.
CONCLUSIONS: In the setting of stateof- the-art coronary care for patients with suspected ACS in the emergency room, NT-proBNP, troponin I, and Lp-PLA2 are effective independent markers for risk stratification that proved to be superior to the TIMI risk score. Lp-PLA2 turned out to be a more effective risk marker than hsCRP in these patients.