Olaf Schulz1, Alexander B Postnikov2, Tatiana I Smolyanova2, Alexey G Katrukha2, Ingolf Schimke3, Allan S Jaffe4. 1. Interventionelle Kardiologie Spandau, Berlin, Germany; Universitätsmedizin Berlin, Charite Campus Mitte, Berlin, Germany. 2. HyTest Ltd., Intelligate 6th floor, Joukahaisenkatu 6, 20520 Turku, Finland. 3. Universitätsmedizin Berlin, Charite Campus Mitte, Berlin, Germany. 4. Mayo Clinic and Medical School, Rochester, MN, USA. Electronic address: jaffe.allan@mayo.edu.
Abstract
OBJECTIVES: We 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. METHODS: In 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. RESULTS: CT-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. CONCLUSION: Despite 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.
OBJECTIVES: We 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. METHODS: In 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. RESULTS: CT-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. CONCLUSION: Despite 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.
Authors: Germán Cediel; Ferran Rueda; Claus Oxvig; Teresa Oliveras; Carlos Labata; Oriol de Diego; Marc Ferrer; M Cruz Aranda-Nevado; Judith Serra-Gregori; Julio Núñez; Cosme García; Antoni Bayes-Genis Journal: Cardiovasc Diabetol Date: 2018-04-30 Impact factor: 9.951
Authors: Alexey A Konev; Alexey V Kharitonov; Fedor N Rozov; Evgeny P Altshuler; Daria V Serebryanaya; Johan Lassus; Veli-Pekka Harjola; Alexey G Katrukha; Alexander B Postnikov Journal: ESC Heart Fail Date: 2020-01-22