Objective: The proteolytic activity of metalloproteinases, proinflammatory enzymes that degrade extracellular matrix, is elevated in lipid-rich atherosclerotic plaques, thereby contributing to plaque fragility and rupture. Pregnancy-associated plasma protein (PAPP-A) is a metalloproteinase, expressed in unstable atherosclerotic plaques, whose circulating levels are elevated in acute coronary syndromes. We evaluated serum PAPP-A levels as a marker of the premature development of atherosclerosis in hyperlipidemic subjects at elevated cardiovascular risk.
Methods and results: Serum PAPP-A levels were determined in asymptomatic hyperlipidemic male subjects (n=64; mean+/-SD age, 51+/-7 years) in whom intima-media thickness (IMT) and lesion status in the carotid artery were evaluated by noninvasive ultrasonography and compared with those of a normolipidemic control group (n=25). No difference was observed in circulating PAPP-A levels between hyperlipidemic subjects and controls (8.99+/-2.93 and 8.03+/-2.75 mIU/L, respectively; mean+/-SD) nor between hyperlipidemic subjects who presented with a luminal obstruction of the carotid artery (9.26+/-2.53 mIU/L) and those who did not (8.85+/-3.29 mIU/L). By contrast, in patients with atheromatous carotid plaques, a positive association between serum levels of PAPP-A and C-reactive protein was observed (P<0.05); moreover, subjects exhibiting hyperechoic or isoechoic, echogenic lesions had significantly higher PAPP-A levels compared with those with hypoechoic lesions (10.32+/-2.72 vs 8.27+/-2.18 mIU/L, P<0.05) and with normolipidemic controls (P<0.05).
Conclusions: Elevated serum PAPP-A levels represent a potential marker of the degree of echogenicity of carotid atherosclerotic plaques in asymptomatic hyperlipidemic patients at high cardiovascular risk and equally of an enhanced local inflammatory state involving remodeling of subendothelial extracellular matrix.