The major initial mechanism of acute coronary syndrome (ACS) is the rupture of the atherosclerotic coronary artery plaque. Clinical signs, electrocardiogram and cardiac troponins, as markers of myocardial ischemia or damage, give an accurate diagnosis, prognostic information and guidance for optimal treatment choices. The useful marker of unstable plaque or the early stage plaque rupture is still missing. 

The primary purpose of this study was to assess the usefulness of pregnancy associated plasma protein A (PAPP-A) and its different forms abundantly expressed in unstable but not in stable atherosclerotic plaque as a prognostic marker in patients presenting with suspected ACS. 

The basic study population comprised 541 consecutive patients who were admitted to the emergency department for symptoms consistent with ACS. Mortality data and data on other cardiac adverse events of nonfatal myocardial infarction, revascularization or hospitalization due to unstable angina, worsening heart failure or stroke, were collected during the 12 months follow up. The blood samples for PAPP-A and other measurements were obtained at admission, 12 h, 24 h and in patients representing with ST-elevation myocardial infarction (STEMI) also at 48 h. The PAPP-A analyses were performed by measuring the total fraction of PAPP-A (totalPAPP-A) in studies I (n=136) and II (n=62). After observing that the elevated PAPP-A concentration in ACS was almost entirely due to the free fraction of PAPP-A (freePAPP-A), a comparison of prognostic performance was done between freePAPP-A and totalPAPP-A measurements (study III, n=267). 

The early elevation (< 24h) of circulating totalPAPP-A in patients who remained cardiac troponin I negative and highly elevated (>10 mIU/L) totalPAPP-A already at admission in patients with STEMI were predictive of higher risk of death or cardiac adverse events. In patients with STEMI the concentration of totalPAPP-A elevated early during the first hours of attack and normalized rapidly. The variability of totalPAPP-A kinetics at 48 hours reflects the success of reperfusion of the culprit artery. FreePAPP-A showed superiority as a prognostic marker compared to totalPAPP-A, giving independent and additive prognostic information when measured at the time of admission in patients hospitalized for non-ST-elevation ACS. 

This study provides evidence of the prognostic performance of PAPP-A, a potential plaque instability marker, in patients representing with ACS. FreePAPP-A is the most prominent form in the circulation during ACS, and its prognostic performance is superior compared to totalPAPP-A.