An Investigation of Activated Factor XII (Fxlla) as a Prognostic Marker.

BACKGROUND Cardiac troponins are sensitive markers for myocardial injury in ACS and even a minor elevation of cardiac troponins is associated with an increased risk for future adverse coronary events. However, a detectable troponin release occurs only in a part of patients admitted with ACS. The clinical outcomes and further prognosis of patients with ACS with absent TnT release vary widely, and the identification of potential high-risk patients with troponin negative ACS still remains a major problem in clinical routine. Therefore, the aim of this study is focused on identifying new biomarkers for risk stratification.

Activated Factor XII: Activated Factor XII leads to contact activation and a number of pathophysiological processes, including hypotension, inflammation, thrombosis and fibrinolysis, are affected by contact activation following the activation of XIIa. Several studies have demonstrated a relation between XIIa and coronary artery heart disease (CAD) (1,2,3,4) and that XIIa levels post MI predict recurrent coronary occlusive events and play a role as an independent risk marker in these patients (5).

However, the detailed mechanisms of XIIa's actions in CAD still remain uncertain although recent findings in animal studies using FXII deficient mice indicate that Factor XII is essential for arterial thrombus formation (6).

Recent research indicates that in-vivo XIIa exists in multiple types and that in-vivo XIIa can exist in the circulation complexed to a variety of other proteins (7). To date, no data exist on the prognostic value of specific in-vivo types of XIIa on outcome in patients with chest pain and/or ACS.

B-type natriuretic peptide: B-type natriuretic peptide (BNP) is a counter-regulatory peptide hormone predominantly synthesized in the ventricular myocardium. BNP is released into the circulation in response to ventricular dilatation and pressure overload, and reflects ventricular wall stress and tissue hypoxia rather than cell injury per se (8, 9). It is a well known marker of left ventricular dysfunction and heart failure (HF), and it provides prognostic information beyond and above left ventricular ejection fraction (LVEF) in patients with an acute coronary syndrome (ACS) (10). This marker of neurohormonal activation and inflammation plays a pivotal role across the spectrum of ACS, including patients with ST-elevation myocardial infarction (MI) and non ST-elevation ACS (NSTE-ACS). Previous studies have demonstrated that BNP measured in the first days after the onset of symptoms independently predicts mortality, HF, and new MI in this patient population. Elevated natriuretic peptides at presentation have been shown to identify patients with ACS who are at higher risk of death and HF, and it adds information to that provided by the troponins (11-13). However, in a low-risk population the association between elevated BNP and survival is attenuated when adjustment is made for echocardiographic variables (in addition to clinical covariates), as shown by Wang and colleagues. In addition, they did not find any association between baseline BNP and the risk of coronary heart disease (CHD) (14).