Startseite Decrease of small dense LDL and lipoprotein-associated phospholipase A2 due to human growth hormone treatment in short children with growth hormone deficiency and small for gestational age status
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Decrease of small dense LDL and lipoprotein-associated phospholipase A2 due to human growth hormone treatment in short children with growth hormone deficiency and small for gestational age status

  • Andreas Krebs , Thomas Kratzin , Jürgen Doerfer , Karl Winkler , Michael Wurm , Natascha von der Werf-Grohmann , Alexandra Krause und Karl Otfried Schwab EMAIL logo
Veröffentlicht/Copyright: 24. Oktober 2015

Abstract

Background: Growth hormone deficiency (GHD) and small for gestational age (SGA) status are associated with cardiovascular risks. We therefore, investigated antiatherogenic effects of growth hormone (GH).

Methods: Subfractions of low-density lipoprotein (LDL) and high-density lipoprotein (HDL), lipoprotein-associated phospholipase A2 (Lp-PLA2), and high-sensitivity C-reactive protein (hsCRP) were measured at baseline, after 8 and 52 weeks of GH treatment in 51 short children born SGA (n=33) or with GHD (n=18).

Results: The overall group showed post-treatment reductions of LDL cholesterol (LDL-C) (p=0.016), small-dense LDL cholesterol (sdLDL-C, p<0.001), Lp-PLA2 (p<0.001), and hsCRP (p=0.005), but increase of HDL2a cholesterol (HDL2a-C, p=0.025). SGA children revealed significant correlations between Lp-PLA2 and LDL-C and sdLDL-C both before and after GH, significant reductions of sdLDL-C, Lp-PLA2, hsCRP, and an increase of HDL2a-C. GHD children showed the same lipid responses, though not significantly.

Conclusions: Children with GHD or born SGA may benefit from GH by growth acceleration and reduction of cardiovascular long-term risks.


Corresponding author: Prof. Dr. Karl Otfried Schwab, MD, Department of Pediatrics and Adolescent Medicine, University Medical Center, Mathilden Str. 1, 79106 Freiburg, Germany, Phone: +4976127044821, Fax: +4976127044140, E-mail:

Acknowledgments

The authors would like to thank all patients and their parents for participating in the study.

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: The study was supported by grants of Pfizer GmbH, Germany.

Employment or leadership: Karl Otfried Schwab is a Member of the PATRO Children study board at Sandoz Biopharmaceuticals. He receives research grants by Ipsen Pharma, Pfizer, Sandoz, Serono-Merck, Synageva and Vitaflo.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Tenhola S, Martikainen A, Rahiala E, Herrgard E, Halonen P, et al. Serum lipid concentrations and growth characteristics in 12-year-old children born small for gestational age. Pediatr Res 2000;48:623–8.10.1203/00006450-200011000-00012Suche in Google Scholar PubMed

2. Salonen M, Tenhola S, Laitinen T, Lyyra-Laitinen T, Romppanen J, et al. Tracking serum lipid levels and the association of cholesterol concentrations, blood pressure and cigarette smoking with carotid artery intima-media thickness in young adults born small for gestational age. Circ J 2010;74:2419–25.10.1253/circj.CJ-10-0398Suche in Google Scholar PubMed

3. Lanes R, Gunczler P, Lopez E, Esaa S, Villaroel O, Revel-Chion R. Cardiac mass and function, carotid intima-media thickness, and lipoprotein levels in growth hormone-deficient adolescents. J Clin Endocrinol Metab 2001;86:1061–5.10.1210/jcem.86.3.7268Suche in Google Scholar PubMed

4. Johannsson G, Albertsson-Wikland K, Bengtsson BA. Discontinuation of growth-hormone (GH) treatment: metabolic effects in GH-deficient and GH-sufficient adolescent patients compared with control subjects. J Clin Endocrinol Metab 1999;84:4516–24.10.1210/jc.84.12.4516Suche in Google Scholar

5. Huxley R, Owen CG, Whincup PH, Cook DG, Rich-Edwards J, et al. Is birth weight a risk factor for ischemic heart disease in later life? Am J Clin Nutr 2007;85:1244–50.10.1093/ajcn/85.5.1244Suche in Google Scholar PubMed

6. Capalbo D, Esposito A, Di Mase R, Barbieri F, Parenti G, et al. Update on early cardiovascular and metabolic risk factors in children and adolescents affected with growth hormone definciency. Minerva Endocrinol 2012;37:379–89.Suche in Google Scholar

7. Lanes R, Soros A, Flores K, Gunczler P, Carillo E, et al. Endothelial function, carotid artery intima-media thickness, epicardial adipose tissue, and left ventricular mass and function in growth hormone deficient adolescents: apparent effects of growth hormone treatment on these parameters. J Clin Endocrinol Metab 2005;90:3978–82.10.1210/jc.2005-0091Suche in Google Scholar PubMed

8. Libby P, Ridker PM, Hansson GK, for the Leducq Transatlantic Network of Atherothrombosis. Inflammation in atherosclerosis. J Am Coll Cardiol 2009;54:2129–38.10.1016/j.jacc.2009.09.009Suche in Google Scholar PubMed PubMed Central

9. Colley KJ, Wolfert RL, Cobble ME. Lipoprotein associated phospholipase A2: role in atherosclerosis and utility as a biomarker or cardiovascular risk. EPMA J 2011;2:27–38.10.1007/s13167-011-0063-4Suche in Google Scholar PubMed PubMed Central

10. Sas T, Mulder P, Hokken-Koelega A. Body composition, blood pressure, and lipid metabolism before and during long-term growth hormone (GH) treatment in children with short starure born small for gestational age either with or without GH deficiency. J Clin Endocrinol Metab 2000;85:3786–92.Suche in Google Scholar

11. Foster C, Burton A, Scholl J, Scott ML, Gunter V, et al. Lipid patterns in treated growth hormone deficient children vs. short stature controls. J Pediatr Endocrinol Metab 2014;27:909–14.Suche in Google Scholar

12. Clayton PE, Cianfarani S, Czernichow P, Johannsson G, Papaport R, et al. CONSENSUS STATEMENT: Management of the child born small for gestational age through to adulthood: a consensus statement of the international societies of Pediatric Endocrinology and the Growth Hormone Research Society. J Clin Endocrinol Metab 2007;92:804–10.10.1210/jc.2006-2017Suche in Google Scholar PubMed

13. GH Research Society. Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: summary statement of the GH Research Society. J Clin Endocrinol Metab 2000;85:3990–93.Suche in Google Scholar

14. Winkler K, Jacob S, Müller-Schewe T, Hoffmann MM, Konrad T. Ezetimibe alone and in combination lowers the concentration of small, dense low-density lipoproteins in type 2 diabetes. Atherosclerosis 2012;220:189–93.10.1016/j.atherosclerosis.2011.10.043Suche in Google Scholar PubMed

15. Schäfer C, Parlesak A, Eckoldt J, Bode C, Bode JC, et al. Beyond HDL-cholesterol increase: phospholipid enrichment and shift from HDL3 to HDL2 in alcohol consumers. J Lipid Res 2007;48:1550–8.10.1194/jlr.M600513-JLR200Suche in Google Scholar

16. Kosaka T, Yamaguchi M, Soda Y, Kishimoto T, Tago A, et al. Spectrophotometric assay for serum platelet-activating factor acetylhydrolase activity. Clin Chim Acta 2000;296:151–61.10.1016/S0009-8981(00)00216-3Suche in Google Scholar

17. Marshall WA, Tanner JM. Variations in the pattern of pubertal changes in boys. Arch Dis Child 1970;45:13–23.10.1136/adc.45.239.13Suche in Google Scholar PubMed PubMed Central

18. Marshall WA, Tanner JM. Variations in the pattern of pubertal changes in girls. Arch Dis Child 1969;44:291–303.10.1136/adc.44.235.291Suche in Google Scholar PubMed PubMed Central

19. Karaman MI, Kaya C, Cascurlu T, Guney S, Ergenekon E. Measurement of pediatric testicular volume with Prader orchidometer: comparison of different hands. Pediatr Surg Int 2005;21:517–20.10.1007/s00383-005-1470-1Suche in Google Scholar PubMed

20. Carmena R, Duriez P, Fruchart J-C. Atherogenic lipoprotein particles in atherosclerosis. Circulation 2004;109(suppl III): III-2–III-7.10.1161/01.CIR.0000131511.50734.44Suche in Google Scholar PubMed

21. Toft-Petersen AP, Tilsted HH, Aaroe J, Rasmussen K, Christensen T, et al. Small dense LDL particles – a predictor of coronary artery disease evaluated by invasive and CT-based techniques: a case-control study. Lipids Health Dis 2011;10:21.10.1186/1476-511X-10-21Suche in Google Scholar PubMed PubMed Central

22. Lind S, Rudling M, Ericsson S, Olivecrona H, Ericsson M, et al. Growth hormone induces low-density lipoprotein clearance but not bile acid synthesis in humans. Arterioscler Vasc Thromb Biol 2004;24:349–56.10.1161/01.ATV.0000110657.67317.90Suche in Google Scholar PubMed

23. Rizzo M, Trepp R, Berneis K, Christ ER. Atherogenic lipoprotein phenotype and low-density lipoprotein size and subclasses in patients with growth hormone deficiency before and after short-term replacement therapy. Eur J Endocrinol 2007;156:361–7.10.1530/EJE-06-0652Suche in Google Scholar PubMed

24. Khera AV, Cuchel M, de la Llera-Moya M, Rodrigues A, Burke MF, et al. Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. N Engl J Med 2011;364:127–35.10.1056/NEJMoa1001689Suche in Google Scholar PubMed PubMed Central

25. Gao X, Yuan S. High density lipoproteins-based therapies for cardiovascular disease. J Cardiovasc Dis Res 2010;1:99–103.10.4103/0975-3583.70898Suche in Google Scholar

26. Joy T, Hegele RA. Is raising HDL a futile strategy for atheroprotection? Nat Rev Drug Discov 2008;7:143–55.10.1038/nrd2489Suche in Google Scholar

27. The Lp-PLA2 Studies Collaboration. Lipoprotein-associated phospholipase A2 and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies. Lancet 2010;375:1536–44.10.1016/S0140-6736(10)60319-4Suche in Google Scholar

28. Rosenson RS, Stafforini DM. Modulation of oxidative stress, inflammation, and atherosclerosis by lipoprotein-associated phospholipase A2. J Lipid Res 2012;53:1767–82.10.1194/jlr.R024190Suche in Google Scholar PubMed PubMed Central

29. Winkler K, Hoffmann MM, Winkelmann BR, Friedrich I, Schäfer G, et al. Lipoprotein-associated phospholipase A2 predicts 5-year cardiac mortality independently of established risk factors and adds prognostic information in patients with low and medium-high high-sensitivity C-reactive protein (The Ludwigshafen Risk and Cardiovascular Health Study). Clin Chem 2007;53:1440–7.10.1373/clinchem.2007.086298Suche in Google Scholar PubMed

30. Ridker PM, MacFadyen JG, Wolfert RL, Koenig W. Relationship of lipoprotein-associated phospholipase A2 mass and activity with incident vascular events among primary prevention patients allocated to placebo or statin therapy: an analyses from the JUPITER trial. Clin Chem 2012;58:877–86.10.1373/clinchem.2011.180281Suche in Google Scholar PubMed

31. Capalbo D, Mattace RG, Esposito A, Di Mase R, Barbieri F, et al. Cluster of cardiometabolic risk factors in children with GH deficiency: a prospective, case-control study. Clin Endocrinol (Oxf) 2014;80:856–62.10.1111/cen.12393Suche in Google Scholar PubMed

Received: 2015-4-8
Accepted: 2015-9-18
Published Online: 2015-10-24
Published in Print: 2016-2-1

©2016 by De Gruyter

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