PAPP-A: a marker of plaque instability. Is it ready for prime time?

Pregnancy-associated plasma protein-A (PAPP-A) is a zinc-binding metalloproteinase that was first identified circulating in the serum of pregnant women, but has recently been suggested to be a predictor of risk for cardiovascular events. Publications on PAPP-A, primarily from the last 4-5 years, were reviewed extensively. A special emphasis was placed on those that address the development of methods for the detection of PAPP-A in human serum/plasma and those that study the diagnostic/prognostic accuracy of PAPP-A in patients with acute coronary syndrome. This review shall focus on the possible mechanism of action of PAPP-A, clinical studies involving PAPP-A, PAPP-A assays and its molecular structure. All clinical studies to date related to the diagnostic/prognostic accuracy of PAPP-A (a total of eight studies) were included. They suggest that elevations in PAPP-A correlate with higher risk for the development of cardiovascular adverse events. However, there are conflicting data as to whether PAPP-A levels correlate with cardiac troponins or C-reactive protein. Thus, there is room for speculation as to whether PAPP-A is involved in inflammatory processes, and as to what its role is in plaque rupture and subsequent cardiac ischemic events. Furthermore, new insights into the molecular structure of PAPP-A could aid in the development of more specific assays that may help unravel the clinical utility of PAPP-A.