Longitudinal changes in C-reactive protein, proform of eosinophil major basic protein, and pregnancy-associated plasma protein-A during weight changes in obese children

Ulrik Lausten-Thomsen; Michael Gamborg; Christine Bøjsøe; Paula L. Hedley; Christian Munch Hagen; Michael Christiansen; Jens-Christian Holm

doi:10.1515/jpem-2014-0249

Article

Longitudinal changes in C-reactive protein, proform of eosinophil major basic protein, and pregnancy-associated plasma protein-A during weight changes in obese children

Ulrik Lausten-Thomsen , Michael Gamborg , Christine Bøjsøe , Paula L. Hedley , Christian Munch Hagen , Michael Christiansen and Jens-Christian Holm

Published/Copyright: December 2, 2014

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 28 Issue 3-4

Abstract

Background: Childhood obesity is associated with several complications, including cardiovascular comorbidity. Several biomarkers, such as high-sensitive C-reactive protein (hs-CRP), proform of eosinophil major basic protein (Pro-MBP) and pregnancy associated plasma protein-A (PAPP-A), have equally been linked to increased cardiovascular susceptibility. This study investigates these biomarkers during weight loss and regain in obese children.

Materials and methods: A longitudinal study during a 12-week weight loss program with a 28 months follow-up was conducted. Anthropometrics and plasma concentrations of hs-CRP, Pro-MBP, and PAPP-A were measured at baseline; at days 14, 33 and 82 during weight loss; and at months 10, 16, and 28 during follow-up.

Results: Fifty-three boys and 62 girls aged 8–15 years with a median body mass index (BMI) standard deviation score (SDS) at baseline of 2.78 (boys), and 2.70 (girls) were included. Ninety children completed the weight loss program and 68 children entered the follow-up program. Pro-MBP and PAPP-A, but not hs-CRP, exhibited individual-specific levels (tracking) during weight loss and regain. The PAPP-A/Pro-MBP correlation was strong, whereas the hs-CRP/PAPP-A correlation was weak during weight fluctuations.

Conclusion: Hs-CRP changes reflect weight changes. PAPP-A and Pro-MBP exhibited tracking during weight perturbations and may contribute as early risk markers of cardiovascular susceptibility.

Keywords: BMI SDS; childhood obesity; hs-CRP; PAPP-A; Pro-MBP; weight loss; weight regain

Corresponding author: Jens-Christian Holm, MD, PhD, Associate Professor, Head of the Children’s Obesity Clinic, Department of Pediatrics, Copenhagen University Hospital, Smedelundsgade 60, 4300 Holbaek, Denmark, Phone: +45 594842-00, Fax: +45 594842-09, E-mail: jhom@regionsjaelland.dk

Acknowledgments

The authors wish to thank Mrs. Oda Troest for providing invaluable expert assistance in data retrieval and handling, as well as Mrs. Pia Lind for her expert technical assistance.

Conflict of interest statement: The authors have no conflicts of interest to disclose.

Statement of financial support: This study has been generously supported by grants from The P. Carl Petersens Foundation, The Health Foundation, The Christmas Stamp Foundation, Danish Medical Research Council, The Queen Louises Children’s Hospital Research Foundation, The King Christian the Xth Foundation, The Rosalie Petersen Foundation, and The Dagmar Marshall Foundation.

References

1. Haslam DW, James WP. Obesity. Lancet 2005;366:1197–209.10.1016/S0140-6736(05)67483-1Search in Google Scholar

2. McGill HC, McMahan CA, Gidding SS. Preventing heart disease in the 21st century: implications of the pathobiological determinants of atherosclerosis in youth (PDAY) study. Circulation 2008;117:1216–27.10.1161/CIRCULATIONAHA.107.717033Search in Google Scholar PubMed

3. Balakrishnan PL. Identification of obesity and cardiovascular risk factors in childhood and adolescence. Pediatr Clin North Am 2014;61:153–71.10.1016/j.pcl.2013.09.013Search in Google Scholar PubMed

4. Reinehr T, Stoffel-Wagner B, Roth CL, Andler W. High-sensitive C-reactive protein, tumor necrosis factor alpha, and cardiovascular risk factors before and after weight loss in obese children. Metabolism 2005;54:1155–61.10.1016/j.metabol.2005.03.022Search in Google Scholar PubMed

5. Soriano-Guillén L, Hernández-García B, Pita J, Domínguez-Garrido N, Del Río-Camacho G, et al. High-sensitivity C-reactive protein is a good marker of cardiovascular risk in obese children and adolescents. Eur J Endocrinol 2008;159:R1–4.10.1530/EJE-08-0212Search in Google Scholar PubMed

6. Skinner AC, Steiner MJ, Henderson FW, Perrin EM. Multiple markers of inflammation and weight status: cross-sectional analyses throughout childhood. Pediatrics 2010;125:e801–9.10.1542/peds.2009-2182Search in Google Scholar PubMed PubMed Central

7. Makita S, Nakamura M, Hiramori K. The association of C-reactive protein levels with carotid intima-media complex thickness and plaque formation in the general population. Stroke 2005;36:2138–42.10.1161/01.STR.0000181740.74005.eeSearch in Google Scholar PubMed

8. Otake H, Shite J, Shinke T, Watanabe S, Tanino Y, et al. Relation between plasma adiponectin, high-sensitivity C-reactive protein, and coronary plaque components in patients with acute coronary syndrome. Am J Cardiol 2008;101:1–7.10.1016/j.amjcard.2007.07.041Search in Google Scholar PubMed

9. Kozan O, Buyukozturk K, Ilerigelen B, Kabakci G, Koylan N. The impact of plasma high-sensitivity C-reactive protein levels on cardiovascular risk stratification of hypertensive patients: results of the ICEBERG study. J Clin Hypertens 2007;9:500–5.10.1111/j.1524-6175.2007.05738.xSearch in Google Scholar PubMed PubMed Central

10. Woelfle J, Roth CL, Wunsch R, Reinehr T. Pregnancy-associated plasma protein A in obese children: relationship to markers and risk factors of atherosclerosis and members of the IGF system. Eur J Endocrinol 2011;165:613–22.10.1530/EJE-11-0423Search in Google Scholar PubMed

11. Liu Z-Y, Zhang J-Y, Sun T-W, Zhang Y-J, Zhang L, et al. Levels of pregnancy-associated plasma protein A in patients with coronary artery disease. Clin Invest Med 2008;31:E85–9.10.25011/cim.v31i2.3368Search in Google Scholar PubMed

12. Iversen KK, Dalsgaard M, Teisner AS, Schoos M, Teisner B, et al. Usefulness of pregnancy-associated plasma protein A in patients with acute coronary syndrome. Am J Cardiol 2009;104:1465–71.10.1016/j.amjcard.2009.07.017Search in Google Scholar PubMed

13. Iversen KK, Teisner AS, Teisner B, Kliem A, Thanning P, et al. Pregnancy associated plasma protein A, a novel, quick, and sensitive marker in ST-elevation myocardial infarction. Am J Cardiol 2008;101:1389–94.10.1016/j.amjcard.2008.01.015Search in Google Scholar PubMed

14. Lund J, Wittfooth S, Qin Q-P, Ilva T, Porela P, et al. Free vs total pregnancy-associated plasma protein A (PAPP-A) as a predictor of 1-year outcome in patients presenting with non-ST-elevation acute coronary syndrome. Clin Chem 2010;56:1158–65.10.1373/clinchem.2009.136960Search in Google Scholar PubMed

15. Consuegra-Sanchez L, Petrovic I, Cosin-Sales J, Holt DW, Christiansen M, et al. Prognostic value of circulating pregnancy-associated plasma protein-A (PAPP-A) and proform of eosinophil major basic protein (pro-MBP) levels in patients with chronic stable angina pectoris. Clin Chim Acta 2008;391:18–23.10.1016/j.cca.2008.01.012Search in Google Scholar PubMed

16. Heider P, Pfäffle N, Pelisek J, Wildgruber M, Poppert H, et al. Is serum pregnancy-associated plasma protein A really a potential marker of atherosclerotic carotid plaque stability? Eur J Vasc Endovasc Surg 2010;39:668–75.10.1016/j.ejvs.2010.03.012Search in Google Scholar PubMed

17. Li X, Liu Q, Zhou T, Zhao S, Zhou S. PAPP-A: A possible pathogenic link to the instability of atherosclerotic plaque. Med Hypotheses 2008;70:597–9.10.1016/j.mehy.2007.05.043Search in Google Scholar PubMed

18. Terkelsen CJ, Oxvig C, Nørgaard BL, Glerup S, Poulsen TS, et al. Temporal course of pregnancy-associated plasma protein-A in angioplasty-treated ST-elevation myocardial infarction patients and potential significance of concomitant heparin administration. Am J Cardiol 2009;103:29–35.10.1016/j.amjcard.2008.08.027Search in Google Scholar PubMed

19. Overgaard MT, Sorensen ES, Stachowiak D, Boldt HB, Kristensen L, et al. Complex of pregnancy-associated plasma protein-A and the proform of eosinophil major basic protein. Disulfide structure and carbohydrate attachment. J Biol Chem 2003;278:2106–17.10.1074/jbc.M208777200Search in Google Scholar PubMed

20. Holm J-C, Gamborg M, Kaas-Ibsen K, Gammeltoft S, Ward L, et al. Time course and determinants of leptin decline during weight loss in obese boys and girls. Int J Pediatr Obes 2007;2:2–10.10.1080/17477160600991509Search in Google Scholar PubMed

21. Holm J-C, Gamborg M, Ward L, Ibsen KK, Gammeltoft S, et al. Longitudinal analysis of leptin variation during weight regain after weight loss in obese children. Obes Facts 2009;2:243–8.Search in Google Scholar

22. Nysom K, Mølgaard C, Hutchings B, Michaelsen KF. Body mass index of 0 to 45-y-old Danes: reference values and comparison with published European reference values. Int J Obes Relat Metab Disord 2001;25:177–84.10.1038/sj.ijo.0801515Search in Google Scholar PubMed

23. Bayes-Genis A, Conover CA, Overgaard MT, Bailey KR, Christiansen M, et al. Pregnancy-associated plasma protein A as a marker of acute coronary syndromes. N Engl J Med 2001;345:1022–9.10.1056/NEJMoa003147Search in Google Scholar PubMed

24. Christiansen M, Jaliashvili I, Overgaard MT, Ensinger C, Obrist P, et al. Quantification and characterization of pregnancy-associated complexes of angiotensinogen and the proform of eosinophil major basic protein in serum and amniotic fluid. Clin Chem 2000;46:1099–105.10.1093/clinchem/46.8.1099Search in Google Scholar

25. Qin QP, Christiansen M, Oxvig C, Pettersson K, Sottrup-Jensen L, et al. Double-monoclonal immunofluorometric assays for pregnancy-associated plasma protein A/proeosinophil major basic protein (PAPP-A/proMBP) complex in first-trimester maternal serum screening for Down syndrome. Clin Chem 1997;43:2323–32.10.1093/clinchem/43.12.2323Search in Google Scholar

26. Diggle P, Zeger SL, Liang K-Y, Heagerty P. Analysis of longitudinal data, 2nd ed. Oxford: Oxford University Press, 2002: 379 pp.Search in Google Scholar

27. Ibrahim JG, Chu H, Chen M-H. Missing data in clinical studies: Issues and methods. J Clin Oncol 2012;30:3297–303.10.1200/JCO.2011.38.7589Search in Google Scholar PubMed PubMed Central

28. Zacho J, Tybjaerg-Hansen A, Jensen JS, Grande P, Sillesen H, et al. Genetically elevated C-reactive protein and ischemic vascular disease. N Engl J Med 2008;359:1897–908.10.1056/NEJMoa0707402Search in Google Scholar PubMed

29. Ridker PM. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation. 2003;107:363–9.10.1161/01.CIR.0000053730.47739.3CSearch in Google Scholar

30. Danesh J, Wheeler JG, Hirschfield GM, Eda S, Eiriksdottir G, et al. C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med 2004;350:1387–97.10.1056/NEJMoa032804Search in Google Scholar PubMed

31. Everett BM, Kurth T, Buring JE, Ridker PM. The relative strength of C-reactive protein and lipid levels as determinants of ischemic stroke compared with coronary heart disease in women. J Am Coll Cardiol 2006;48:2235–42.10.1016/j.jacc.2006.09.030Search in Google Scholar PubMed PubMed Central

32. Oude Luttikhuis H, Baur L, Jansen H, Shrewsbury VA, O’Malley C, et al. Interventions for treating obesity in children. Cochrane Database Syst Rev 2009;1:CD001872.10.1002/14651858.CD001872.pub2Search in Google Scholar PubMed

Received: 2014-6-9

Accepted: 2014-9-29

Published Online: 2014-12-2

Published in Print: 2015-3-1

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Articles in the same Issue

https://doi.org/10.1515/jpem-2014-0249

Keywords for this article

BMI SDS; childhood obesity; hs-CRP; PAPP-A; Pro-MBP; weight loss; weight regain