Clinical differences between total PAPP-A and measurements specific for the products of free PAPP-A activity in patients with stable cardiovascular disease

Abstract

ObjectivesWe have previously reported that increases in total pregnancy-associated plasma protein-A (PAPP-A) which are thought to be indicative of vulnerable plaques and thus poor outcomes predict outcomes in patients with stable coronary artery disease. We hypothesized that the determination of CT- and NT-fragments of insulin-like growth factor binding protein 4 (CT- and NT-IGFBP4) which should be indicative of free PAPP-A would result in better performance. MethodsIn 229 stable cardiovascular patients with indication for heart catheterization after performance of a stress test and an echocardiogram, CT- and NT-IGFBP4 were measured. Their values were investigated in relation to clinical characteristics, findings of noninvasive investigations, laboratory data and coronary angiography as well as to outcomes after a follow-up of 1094±307days. ResultsCT-IGFBP4 values were independently predicted by patients with B-type (p=0.0069) or complex coronary lesions (p=0.0445). B-type and vulnerable coronary lesions were independently predicted by levels of CT-IGFBP4≥a cutoff of 31.55ng/mL derived from ROC analysis (p=0.0090 and 0.0480). NT-IGFBP4 was not predictive of coronary characteristics. Both IGFBP4 fragments were strongly dependent on age and renal function and were not predictive of outcomes. ConclusionDespite the relation of CT-IGFBP4 to a more severe coronary artery disease, CT- and NT-IGFBP4, in contrast to our report based on total PAPP-A, failed to predict any long-term outcomes in patients with stable cardiovascular disease. Further knowledge about the interaction of the PAPP-A-insulin-like growth factor system is needed to explain values of IGFBP4 fragments in these patients.