The Role of Insulin-Like Growth Factor-1 and Pregnancy-Associated Plasma Protein-A in Diagnosis of Acute Coronary Syndrome and Its Related Morbidities
Abstract
Introduction: Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase that plays a role in atherosclerotic plaque destabilization. In recent studies, insulin-like growth factor-1 (IGF-1) has been introduced as a mediator of atherosclerosis. PAPP-A and IGF-1 level may be important diagnostic indicators of acute coronary syndrome (ACS). Objective: The present study tried to assess the diagnostic role of IGF-1 and PAPP-A biomarkers in ACS spectrum. Methods: The serum level of IGF-1, PAPP-A and troponin I was determined in 121 consecutive patients with ACS. Relationships were assessed by t-test, ANOVA and the non-parametric equivalent. Accuracy of biomarkers was measured by the area under the ROC curve (AUC) and optimal cut-off points to diagnose STEMI and NSTEMI using Youden index. Results: In patients with acute ST segment elevation myocardial infarction (STEMI), all of these three biomarkers were significantly higher than those in patients with unstable angina (P= 0.028 for IGF-1, P<0.001 for PAPP-A and Troponin-I). Mean level of IGF-1 in patients with renal failure was significantly higher than that in patients without renal failure (137.9±35.1 vs 105.1±46.9, P=0.003), but PAPP-A and serum Troponin-I level had no significant difference in renal failure groups (P>0.05). ROC curve analysis showed that after Troponin-I, PAPP-A was a good discriminator between patients with STEMI and patients with unstable angina (AUC=0.79). Optimum cut-off value for PAPP-A was found to be 89.2 ng/ml, with sensitivity and specificity of 66.7% and 83.8%, respectively. Conclusion: PAPP-A can be a novel biomarker for both identification of patients with STEMI and risk stratification in patients with ACS.
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2. Twickler MT, Cramer JM, Koppeschaar HP. Unraveling Reaven’s syndrome X: serum insulin-like growth factor-I and cardiovascular disease. Circulation. 2003;107(20):e190-2.
3. Spies M, Nesic O, Barrow RE, Perez-Polo JR, Herndon DN. Liposomal IGF-1 gene transfer modulates pro-and anti-inflammatory cytokine mRNA expression in the burn wound. Gene Ther. 2001;8(18):1409-15.
4. Grant MB, Wargovich TJ, Bush DM, Player DW, Caballero S, Foegh M, et al. Expression of IGF-1, IGF-1 receptor and TGF-β following balloon angioplasty in atherosclerotic and normal rabbit iliac arteries: An immunocytochemical study. Regul Pept. 1999;79(1):47-53.
5. Liu K, Ying Z, Qi X, Shi Y, Tang Q. MicroRNA-1 regulates the proliferation of vascular smooth muscle cells by targeting insulin-like growth factor 1. Int J Mol Med. 2015;36(3):817-24.
6. Sekuri C, Arslan O, Utük O, Bayturan O, Onur E, Tezcan UK, et al. Serum level of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in acute coronary syndromes and relationship with prognosis. Anadolu Kardiyol Derg. 2004;4(3):209-12.
7. Conti E, Andreotti F, Sestito A, Riccardi P, Menini E, Crea F, et al. Reduced levels of insulin-like growth factor-1 in patients with angina pectoris, positive exercise stress test, and angiographically normal epicardial coronary arteries. Am J Cardiol. 2002;89(8):973-5.
8. Bayes-Genis A, Conover CA, Schwartz RS. The insulin-like growth factor axis a review of atherosclerosis and restenosis. Circ Res. 2000 Feb 4;86(2):125-30.
9. Schini-Kerth VB. Dual effects of insulin-like growth factor-I on the constitutive and inducible nitric oxide (NO) synthase-dependent formation of NO in vascular cells. J Endocrinol Invest. 1999;22(5 Suppl):82-8.
10. Overgaard MT, Haaning J, Boldt HB, Olsen IM, Laursen LS, Christiansen M, et al. Expression of recombinant human pregnancy-associated plasma protein-A and identification of the proform of eosinophil major basic protein as its physiological inhibitor. J Biol Chem. 2000;275(40):31128-33.
11. Kalousová M, Zima T, Krane V, März W, Wanner C, Tesař V, et al. Pregnancy-associated plasma protein A associates with cardiovascular events in diabetic hemodialysis patients. Atherosclerosis. 2014;236(2):263-9.
12. Bayes-Genis A, Conover CA, Overgaard MT, Bailey KR, Christiansen M, Holmes Jr DR, et al. Pregnancy-associated plasma protein A as a marker of acute coronary syndromes. New England Journal of Medicine. 2001;345(14):1022-9.
13. Lund J, Qin QP, Ilva T, Pettersson K, Voipio-Pulkki LM, Porela P, et al. Circulating pregnancy-associated plasma protein a predicts outcome in patients with acute coronary syndrome but no troponin I elevation. Circulation. Circulation. 2003;108(16):1924-6.
14. Heeschen C, Dimmeler S, Hamm CW, Fichtlscherer S, Simoons ML, Zeiher AM, et al. Pregnancy-associated plasma protein-A levels in patients with acute coronary syndromes: comparison with markers of systemic inflammation, platelet activation, and myocardial necrosis. J Am Coll Cardiol. 2005;45(2):229-37.
15. Wu XF, Yang M, Qu AJ, Mintz GS, Yang Y, Shang YP, et al. 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. Medicine (Baltimore). 2016;95(3):e2563.
16. Liu ZY, Zhang JY, Sun TW, Zhang YJ, Zhang L, Wang LX. Levels of pregnancy-associated plasma protein A in patients with coronary artery disease. Clin Invest Med. 2008;31(2):E85-9.
17. Amsterdam EA, Wenger NK, Brindis RG, Casey DE Jr, Ganiats TG, Holmes DR Jr, et al. 2014 AHA/ACC Guideline for the management of patients with non-ST-elevation acute coronary syndrom: a report of the American Collegen Practice Guidline. J Am Coll Cardiol. 2014;64(24):e139-e228
18. Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr,. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-Elevationmyocardial infarction: a report of the American College of Cardiology/American heartassociation Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelinesfor the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J Am Coll Cardiol. 2007;50(7):e1-e157.
19. O'Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, de Lemos JA, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidlines. J Am Coll Cardiol. 2013;61(4):485-510.
20. Rapid test for the qualitative determination of Cardiac Troponin I (cTnI) in human whole blood, serum and plasma,2011, available at: www.demeditec.com
21. Baillard C, Boussarsar M, Fosse JP, Girou E, Le Toumelin P, Cracco C, et al. Cardiac troponin I in patients with severe exacerbation of chronic obstructive pulmonary disease. Intensive Care Med. 2003;29(4):584-9.
22. Levey AS, Inker L. Definition and staging of chronic kidney disease in adults. Curhan, GC. 2013.
23. Kim Y, Garvin J, Goldstein MK, Meystre SM. Classification of Contextual Use of Left Ventricular Ejection Fraction Assessments. Stud Health Technol Inform. 2015;216:599-603.
24. Grundy SM, Brewer HB, Cleeman JI, Smith SC, Lenfant C, American Heart Association, et al. Definition of metabolic syndrome report of the National Heart, Lung, and Blood Institute/American Heart Association Conference on scientific issues related to definition. Circulation. 2004;109(3):433-8.
25. Gomez JM, Maravall FJ, Gomez N, Navarro MA, Casamitjana R, Soler J. Interactions between serum leptin, the insulin‐like growth factor‐I system, and sex, age, anthropometric and body composition variables in a healthy population randomly selected. Clin Endocrinol (Oxf). 2003;58(2):213-9.
26. Aguirre GA, De Ita JR, de la Garza RG, Castilla-Cortazar I. Insulin-like growth factor-1 deficiency and metabolic syndrome. J Transl Med. 2016;14:3.
27. Teppala S, Shankar A, Sabanayagam C. Association between IGF-1 and chronic kidney disease among US adults. Clin Exp Nephrol. 2010;14(5):440-4..
28. Paolisso G, Rizzo MR, Mazziotti G, Tagliamonte MR, Gambardella A, Rotondi M, et al. Advancing age and insulin resistance: role of plasma tumor necrosis factor-α. Am J Physiol. 1998;275(2):E294-9.
29. Davani EY, Brumme Z, Singhera GK, Côté HC, Harrigan PR, Dorscheid DR. Insulin-like growth factor-1 protects ischemic murine myocardium from ischemia/reperfusion associated injury. Crit Care. 2003;7(6):R176-83.
30. Yalcin AA, Topuz M, Biyik I, Akturk IF, Celik O, Isıksacan N, et al. Role of insulin-like growth factor 1 in stent thrombosis under effective dual antiplatelet therapy. Postepy Kardiol Interwencyjnej. 2014;10(4):242-9.
31. Burchardt P, Gozdzicka-Jozefiak A, Zurawski J, Nowak W, Durzynska J, Link R, et al. Are elevated levels of IGF-1 caused by coronary arteriesoclerosis?: Molecular and clinical analysis. Protein J. 2010;29(8):538-44.
32. Vaessen N, Heutink P, Janssen JA, Witteman JC, Testers L, Hofman A, et al. A polymorphism in the gene for IGF-I functional properties and risk for type 2 diabetes and myocardial infarction. Diabetes. 2001;50(3):637-42.
33. Li Q, Li B, Wang X, Leri A, Jana KP, Liu Y, et al. Overexpression of insulin-like growth factor-1 in mice protects from myocyte death after infarction, attenuating ventricular dilation, wall stress, and cardiac hypertrophy. J Clin Invest. 1997;100(8):1991-9.
34. Konev AA, Smolyanova TI, Kharitonov AV, Serebryanaya DV, Kozlovsky SV, Kara AN, et al. Characterization of endogenously circulating IGFBP-4 fragments—Novel biomarkers for cardiac risk assessment. Clin Biochem. 2015;48(12):774-80.
35. Hjortebjerg R, Lindberg S, Hoffmann S, Jensen JS, Oxvig C, Bjerre M, et al. PAPP-A and IGFBP-4 fragment levels in patients with ST-elevation myocardial infarction treated with heparin and PCI. Clin Biochem. 2015;48(4-5):322-8.
36. Shehata M. Pregnancy-Associated Plasma Protein-A Levels and Coronary Angiographic Features in Acute Coronary Syndrome Patients. J Angiol. 2014;2014:420937.
37. Bonaca MP, Scirica BM, Sabatine MS, Jarolim P, Murphy SA, Chamberlin JS, et al. Prospective evaluation of pregnancy-associated plasma protein-a and outcomes in patients with acute coronary syndromes. J Am Coll Cardiol. 2012;60(4):332-8.
38. Gururajan P, Gurumurthy P, Nayar P, Rao GSN, Babu RS, Sarasabharati A, et al. Pregnancy associated plasma protein-A (PAPP-A) as an early marker for the diagnosis of acute coronary syndrome. Indian Heart J. 2012;64(2):141-5.
39. Laterza OF, Cameron SJ, Chappell D, Sokoll LJ, Green GB. Evaluation of pregnancy-associated plasma protein A as a prognostic indicator in acute coronary syndrome patients. Clin Chim Acta. 2004;348(1-2):163-9.
2. Twickler MT, Cramer JM, Koppeschaar HP. Unraveling Reaven’s syndrome X: serum insulin-like growth factor-I and cardiovascular disease. Circulation. 2003;107(20):e190-2.
3. Spies M, Nesic O, Barrow RE, Perez-Polo JR, Herndon DN. Liposomal IGF-1 gene transfer modulates pro-and anti-inflammatory cytokine mRNA expression in the burn wound. Gene Ther. 2001;8(18):1409-15.
4. Grant MB, Wargovich TJ, Bush DM, Player DW, Caballero S, Foegh M, et al. Expression of IGF-1, IGF-1 receptor and TGF-β following balloon angioplasty in atherosclerotic and normal rabbit iliac arteries: An immunocytochemical study. Regul Pept. 1999;79(1):47-53.
5. Liu K, Ying Z, Qi X, Shi Y, Tang Q. MicroRNA-1 regulates the proliferation of vascular smooth muscle cells by targeting insulin-like growth factor 1. Int J Mol Med. 2015;36(3):817-24.
6. Sekuri C, Arslan O, Utük O, Bayturan O, Onur E, Tezcan UK, et al. Serum level of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in acute coronary syndromes and relationship with prognosis. Anadolu Kardiyol Derg. 2004;4(3):209-12.
7. Conti E, Andreotti F, Sestito A, Riccardi P, Menini E, Crea F, et al. Reduced levels of insulin-like growth factor-1 in patients with angina pectoris, positive exercise stress test, and angiographically normal epicardial coronary arteries. Am J Cardiol. 2002;89(8):973-5.
8. Bayes-Genis A, Conover CA, Schwartz RS. The insulin-like growth factor axis a review of atherosclerosis and restenosis. Circ Res. 2000 Feb 4;86(2):125-30.
9. Schini-Kerth VB. Dual effects of insulin-like growth factor-I on the constitutive and inducible nitric oxide (NO) synthase-dependent formation of NO in vascular cells. J Endocrinol Invest. 1999;22(5 Suppl):82-8.
10. Overgaard MT, Haaning J, Boldt HB, Olsen IM, Laursen LS, Christiansen M, et al. Expression of recombinant human pregnancy-associated plasma protein-A and identification of the proform of eosinophil major basic protein as its physiological inhibitor. J Biol Chem. 2000;275(40):31128-33.
11. Kalousová M, Zima T, Krane V, März W, Wanner C, Tesař V, et al. Pregnancy-associated plasma protein A associates with cardiovascular events in diabetic hemodialysis patients. Atherosclerosis. 2014;236(2):263-9.
12. Bayes-Genis A, Conover CA, Overgaard MT, Bailey KR, Christiansen M, Holmes Jr DR, et al. Pregnancy-associated plasma protein A as a marker of acute coronary syndromes. New England Journal of Medicine. 2001;345(14):1022-9.
13. Lund J, Qin QP, Ilva T, Pettersson K, Voipio-Pulkki LM, Porela P, et al. Circulating pregnancy-associated plasma protein a predicts outcome in patients with acute coronary syndrome but no troponin I elevation. Circulation. Circulation. 2003;108(16):1924-6.
14. Heeschen C, Dimmeler S, Hamm CW, Fichtlscherer S, Simoons ML, Zeiher AM, et al. Pregnancy-associated plasma protein-A levels in patients with acute coronary syndromes: comparison with markers of systemic inflammation, platelet activation, and myocardial necrosis. J Am Coll Cardiol. 2005;45(2):229-37.
15. Wu XF, Yang M, Qu AJ, Mintz GS, Yang Y, Shang YP, et al. 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. Medicine (Baltimore). 2016;95(3):e2563.
16. Liu ZY, Zhang JY, Sun TW, Zhang YJ, Zhang L, Wang LX. Levels of pregnancy-associated plasma protein A in patients with coronary artery disease. Clin Invest Med. 2008;31(2):E85-9.
17. Amsterdam EA, Wenger NK, Brindis RG, Casey DE Jr, Ganiats TG, Holmes DR Jr, et al. 2014 AHA/ACC Guideline for the management of patients with non-ST-elevation acute coronary syndrom: a report of the American Collegen Practice Guidline. J Am Coll Cardiol. 2014;64(24):e139-e228
18. Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr,. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-Elevationmyocardial infarction: a report of the American College of Cardiology/American heartassociation Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelinesfor the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J Am Coll Cardiol. 2007;50(7):e1-e157.
19. O'Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, de Lemos JA, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidlines. J Am Coll Cardiol. 2013;61(4):485-510.
20. Rapid test for the qualitative determination of Cardiac Troponin I (cTnI) in human whole blood, serum and plasma,2011, available at: www.demeditec.com
21. Baillard C, Boussarsar M, Fosse JP, Girou E, Le Toumelin P, Cracco C, et al. Cardiac troponin I in patients with severe exacerbation of chronic obstructive pulmonary disease. Intensive Care Med. 2003;29(4):584-9.
22. Levey AS, Inker L. Definition and staging of chronic kidney disease in adults. Curhan, GC. 2013.
23. Kim Y, Garvin J, Goldstein MK, Meystre SM. Classification of Contextual Use of Left Ventricular Ejection Fraction Assessments. Stud Health Technol Inform. 2015;216:599-603.
24. Grundy SM, Brewer HB, Cleeman JI, Smith SC, Lenfant C, American Heart Association, et al. Definition of metabolic syndrome report of the National Heart, Lung, and Blood Institute/American Heart Association Conference on scientific issues related to definition. Circulation. 2004;109(3):433-8.
25. Gomez JM, Maravall FJ, Gomez N, Navarro MA, Casamitjana R, Soler J. Interactions between serum leptin, the insulin‐like growth factor‐I system, and sex, age, anthropometric and body composition variables in a healthy population randomly selected. Clin Endocrinol (Oxf). 2003;58(2):213-9.
26. Aguirre GA, De Ita JR, de la Garza RG, Castilla-Cortazar I. Insulin-like growth factor-1 deficiency and metabolic syndrome. J Transl Med. 2016;14:3.
27. Teppala S, Shankar A, Sabanayagam C. Association between IGF-1 and chronic kidney disease among US adults. Clin Exp Nephrol. 2010;14(5):440-4..
28. Paolisso G, Rizzo MR, Mazziotti G, Tagliamonte MR, Gambardella A, Rotondi M, et al. Advancing age and insulin resistance: role of plasma tumor necrosis factor-α. Am J Physiol. 1998;275(2):E294-9.
29. Davani EY, Brumme Z, Singhera GK, Côté HC, Harrigan PR, Dorscheid DR. Insulin-like growth factor-1 protects ischemic murine myocardium from ischemia/reperfusion associated injury. Crit Care. 2003;7(6):R176-83.
30. Yalcin AA, Topuz M, Biyik I, Akturk IF, Celik O, Isıksacan N, et al. Role of insulin-like growth factor 1 in stent thrombosis under effective dual antiplatelet therapy. Postepy Kardiol Interwencyjnej. 2014;10(4):242-9.
31. Burchardt P, Gozdzicka-Jozefiak A, Zurawski J, Nowak W, Durzynska J, Link R, et al. Are elevated levels of IGF-1 caused by coronary arteriesoclerosis?: Molecular and clinical analysis. Protein J. 2010;29(8):538-44.
32. Vaessen N, Heutink P, Janssen JA, Witteman JC, Testers L, Hofman A, et al. A polymorphism in the gene for IGF-I functional properties and risk for type 2 diabetes and myocardial infarction. Diabetes. 2001;50(3):637-42.
33. Li Q, Li B, Wang X, Leri A, Jana KP, Liu Y, et al. Overexpression of insulin-like growth factor-1 in mice protects from myocyte death after infarction, attenuating ventricular dilation, wall stress, and cardiac hypertrophy. J Clin Invest. 1997;100(8):1991-9.
34. Konev AA, Smolyanova TI, Kharitonov AV, Serebryanaya DV, Kozlovsky SV, Kara AN, et al. Characterization of endogenously circulating IGFBP-4 fragments—Novel biomarkers for cardiac risk assessment. Clin Biochem. 2015;48(12):774-80.
35. Hjortebjerg R, Lindberg S, Hoffmann S, Jensen JS, Oxvig C, Bjerre M, et al. PAPP-A and IGFBP-4 fragment levels in patients with ST-elevation myocardial infarction treated with heparin and PCI. Clin Biochem. 2015;48(4-5):322-8.
36. Shehata M. Pregnancy-Associated Plasma Protein-A Levels and Coronary Angiographic Features in Acute Coronary Syndrome Patients. J Angiol. 2014;2014:420937.
37. Bonaca MP, Scirica BM, Sabatine MS, Jarolim P, Murphy SA, Chamberlin JS, et al. Prospective evaluation of pregnancy-associated plasma protein-a and outcomes in patients with acute coronary syndromes. J Am Coll Cardiol. 2012;60(4):332-8.
38. Gururajan P, Gurumurthy P, Nayar P, Rao GSN, Babu RS, Sarasabharati A, et al. Pregnancy associated plasma protein-A (PAPP-A) as an early marker for the diagnosis of acute coronary syndrome. Indian Heart J. 2012;64(2):141-5.
39. Laterza OF, Cameron SJ, Chappell D, Sokoll LJ, Green GB. Evaluation of pregnancy-associated plasma protein A as a prognostic indicator in acute coronary syndrome patients. Clin Chim Acta. 2004;348(1-2):163-9.
| Files | ||
| Issue | Vol 4 No 2 (2020): Spring (April) | |
| Section | Original article | |
| PMCID | PMC7163271 | |
| PMID | 32322786 | |
| Keywords | ||
| Acute Coronary Syndrome Insulin-Like Growth Factor I Morbidity Pregnancy-Associated Plasma Protein-A | ||
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How to Cite
1.
Mehrpooya M, Malekkandi M, Arabloo M, Zebardast J, Sattartabar B. The Role of Insulin-Like Growth Factor-1 and Pregnancy-Associated Plasma Protein-A in Diagnosis of Acute Coronary Syndrome and Its Related Morbidities. Front Emerg Med. 2019;4(2):e18.
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