Level of Pregnancy-associated Plasma Protein-A Correlates With Coronary Thin-cap Fibroatheroma Burden in Patients With Coronary Artery Disease: Novel Findings From 3-Vessel Virtual Histology Intravascular Ultrasound Assessment

Abstract

Pregnancy-associated plasma protein-A (PAPP-A) level is an independent predictor of acute cardiovascular event occurrence. To test the hypothesis that increased PAPP-A levels would be associated with a higher burden of coronary thin-cap fibroatheroma (TCFA) thereby underlying the heightened risk for cardiovascular events in patients with coronary artery disease; 154 patients (462 vessels and 975 plaques) with stable angina or non-ST-segment elevation acute coronary syndrome (NSTE-ACS) referred for percutaneous coronary intervention were assessed using 3-vessel virtual histology (VH)-intravascular ultrasound (IVUS). Thin-cap fibroatheroma virtual histology was defined as focal, necrotic core (NC)-rich (≥10% of cross-sectional area) plaques in contact with the lumen, and plaque burden ≥40%. Pregnancy-associated plasma protein-A levels were determined by sandwich enzyme-linked immunosorbent assay, and patients were divided into 3 groups based on PAPP-A level tertiles. Although the highest PAPP-A level tertile was not associated with 3-vessel plaque number, it was associated with 3-vessel VH-TCFA number and necrotic core volume. Patients with ≥3 VH-TCFAs had a higher PAPP-A level than patients with 1 to 3 VH-TCFAs or without any VH-TCFA (13.3 ± 11.8 versus 7.8 ± 4.7 versus 7.4 ± 4.7 mIU/L, P < 0.001, respectively). Moreover, PAPP-A level was an independent predictor of higher total number of VH-TCFAs (OR 1.18; 95% CI 1.07-1.29, P = 0.001). This VH-IVUS study demonstrated, for the first time to our knowledge, that higher PAPP-A levels are associated with higher 3-vessel TCFA burden in patients with coronary artery disease. Pregnancy-associated plasma protein-A, therefore, might be a useful serum biomarker to predict increased coronary TCFA burden and plaque instability.

FIGURE 1

PAPP-A level for each tertile of necrotic core amount. Pregnancy-associated plasma protein-A level was significantly higher in the highest tertile than in other groups. MLA = minimum lumen area, NC = necrotic core, PAPP-A = pregnancy-associated plasma protein-A.

FIGURE 2

Pregnancy-associated plasma protein-A level for each number of TCFAs. The number of TCFAs at MLA, culprit vessel or 3-vessel strongly correlated with PAPP-A level; the more TCFAs, the higher the PAPP-A level. MLA = minimum lumen area, NC = necrotic core, PAPP-A = pregnancy-associated plasma protein-A, TCFA = thin-cap fibroatheroma.

FIGURE 3

Kaplan–Meier curves of event-free survival for major adverse cardiac events according to pregnancy-associated plasma protein-A tertiles. The log rank test showed a significant difference in the cumulative event-free survival among pregnancy-associated plasma protein-A tertiles (P = 0.015).