The Effect of Growth Hormone Release (GHR) on Coronary Artery Disease Patients who are not Suitable for Mechanical Revascularization

Abstract

Objective: We evaluated in our study the effects of Growth Hormon Release (GHR) which is claimed as a natural modulator of Growth Hormone (GH) secretion at pituitary level, on coronary artery disease patients who don't have the possibility of mechanical revascularization. Materials and Methods: 67 patients who don't have the chance of mechanical revascularization due to the results of angiographic analysis were included in the study. After the standardization of anti-ischemia treatment, patients were evaluated clinically for basal homodynamic data, life quality criteria, limits of exertional capacity, and Duke treadmill scores (DTS) and then for 12 weeks GHR was given to the first group (n:38) and placebo was given to the other group(n:36). At the end of 12 weeks besides all the hemodynamic parameters; evaluation of all the patients was repeated for life quality criteria, limits of exertional capacity and DTS. Results: Basal clinical demographic characteristics of two groups were similar (p>0.05). Although 41 % decrease in weekly nitrate consumption (p:0.01), 39% decrease in weekly angina pectoris attacks (p:0.01), an increase of 98 seconds (p:0.01) in the mean period to 1 mm ST depression in treadmill and 40 % improvement in DTS (p:0.02) were seen in GHR group, there was no statistically significant change in placebo group (p>0.05). Conclusion: We believe that added-on GHR therapy on standard anti-ischemia treatment protocol in patients who don't have the chance of mechanical revascularization may improve the quality of life.

Keywords

• -

Growth Hormone Release (GHR)'in Mekanik Revaskülarizasyon İmkanı Olmayan Koroner Arter Hastalıklı Vakalar Üzerindeki Etkisi

Öz

Amaç: Çalışmamızda hipofizer seviyede doğal Growth Hormone (GH) sekresyonuna yol açtığı iddia edilen Growth Hormon Release (GHR)'nin mekanik revaskülarizasyon imkanı olmayan iskemik kalp hastalıklı hastalar üzerindeki etkisi araştırıldı. Gereç ve Yöntemler: Çalışmaya anjiyografik analizler sonucu mekanik revaskülarizasyon imkanı olmayan toplam 67 hasta alındı. Hastaların anti-iskemik tedavileri standardize edildikten ve bazal hemodinamik verilerini de içeren klinik bilgileri, yaşam kalitesi ölçütleri, egzersizyonel kapasite sınırları ve treadmill risk skorları (Duke treadmil skoru) tespit edildikten sonra, 12 hafta süre ile bir grup hastaya (n: 38,) GHR; diğer bir grup hastaya ise (n:36) uygun plesebo verildi. On ikinci haftanın sonunda ise tüm hastaların hemodinamik parametreleri ile birlikte yaşam kalitesi ölçütleri, egzersiz kapasitesi sınırları ve treadmil risk skorları tekrar incelendi. Bulgular: Grupların bazal klinik demografik özellikleri benzerdi (p>0.05). Bununla birlikte, tedavi sonrası GHR grubunda haftalık nitrat kullanımında %41 oranında azalma (5.4±4.5 tb'den 3.2±4.5 tb'te, p:0.01), haftalık angina pektoris atağında %39 oranında azalma (5.1±2.6'ten 3.1±1.5'e, p:0.01), 1 mm ST segment depresyonuna kadar geçen ortalama sürede 98 saniye uzama (185 ±142'snden 283±155'snye, p:0.01) ve Duke treadmil skorunda%40 oranında düzelme (-8.8 ±7.8'den -5.3±3.9'a, p:0.02) görülmesine rağmen; plesebo grubunda istatistiksel açıdan anlamlı herhangi bir değişiklik izlenmedi (p>0,05). Sonuç: GHR'nin standart anti-iskemik tedavi protokolüne ilave edilmesiyle mekanik revaskülarizasyon imkanı olmayan hastalarda yaşam kalitesini düzeltebileceği kanaatine varıldı.

Anahtar Kelimeler

• Koroner arter hastalığı, growth hormone release, treadmil risk skoru

Kaynakça

1. Cone RD, Low MJ, Elmguist JK, and Cameron JL. Neuroendocrinology. In Larsen PR, Kronenberg HM, Melmed S, and Polonsky KS. Williams Textbook of Endocrinology. 10th ed. Philadelphia, Pennsylvania: Saunders; 2003:81-157. 2. Isaksson OG, Edene S, and Jansson JO. Mode of action of pituitary growth hormone on target cells. Annu Rev Physiol 1985; 47: 483-499.
2. Ohlsson C, Sjögren K, Jansson JO, and Isaksson O. The relative importance of endocrine versus autocrine/paracrine insulin-like growth factor-I in the regulation of body growth. Pediatr Nephrol 2000; 14: 541-543.
3. Angelin B and Rudling M. Growth hormone and hepatic lipoprotein metabolism. Curr Opin Lipidol 1994; 5: 160-165.
4. Davidsson MB. Effect of growth hormone on carbohydrate and lipid metabolism. Endocr Rev 1987; 8: 115-131,
5. Jörgensen J, Möller N, Wolthers T, et al. Fuel metabolism in growth hormone deficient adults. Metabolism 1995; 44:103107.
6. Strobl JS, Thomas MJ. Human growt hormone. Pharmacological Reviews 1994,46:1-34.
7. Corpas F, Harman S, and Blackman M. Human growth hormone and human aging. Endocr Rev 1993; 14: 20-39.
8. Kelijman M. Age-related alterations of the growth hormone/ insulin-like growth-factor I axis. J Am Geriatr Soc 1991;39: 295-307.

9. Rudman D. Occasional hypothesis: growth hormone, body composition, and ageing. J Am Geriatr Soc 1985; 33: 800-807. 11. Berneis K and Keller U. Metabolic actions of growth hormone: direct and indirect. Baillieres Clin Endocrinol Metab 1996; 14: 337-352.
10. Richelsen B. Action of growth hormone in adipose tissue. Horm Res 1997; 48: 105-110.
11. Ito H, Hiroe M, Hirata Y, et al. Insulin-like growth factor-I induces hypertrophy with enhanced expression of muscle specific genes in cultured rat cardiomyocytes. Circulation 1993; 87: 1715-1721.
12. Guse AH, Kess W, Funk B, et al. Identification and characterization of insulin-like growth factor receptors on adult rat myocytes: linkage to inositol-1,4,5-triphosphate formation. Endocrinology 1992; 130: 145-151.
13. Vetter U, Kupferschmid C, Lang D, Pents S. Insuline-like growth factors and insulin increase the contractility of neonatal rat cardiocytes in vitro. Basic Res Cardiol 1988; 83:647-654.
14. Timsit J, Riou B, Bertherat J, et al. Effects of chronic growth hormone hypersecretion on intrinsic contractility, energetics, isomyosin pattern and myosin-adenosine triphosphatase activity of rat left ventricle. J Clin Invast 1990; 86: 507-515.
15. Carrol PV and Christ ER. Growth hormone deficiency in adulthood an the effects of growth hormone replacement: a review. J Clin Endocrinol Metab 1998; 83: 382-395.
16. Beshyah SA and Johnston DG. Cardiovascular disease and risk factors in adults with hypopituitarism. Clin Endocrinol (Oxf)1999; 50: 1-15.
17. Vence ML and Mauras N. Growth hormone thrapy in adults and childeren. N Engl J Med 1999; 341:1206-1216.Fırat Tıp Dergisi 2010;15(1): 21-26
18. Amato G,m Carella C, Fazio S, et al. Body composition, bone metabolism, and heart structure and function in growth hormone-deficient adults before and after growth hormone replacement therapy at low doses. J Clin Endocrinol Metab 1993; 77: 1671-1676.
19. Cittadini A, Cuocolo A, Merola B, et al. Impaired cardiac performance in GH-deficient adults and its improvement after GH replacement. Am J Physiol 1994; 267: E219-E225.
20. Cuocolo A, Nicolai E, Colao A, et al. Improved left ventricular function after growth hormone replacement in patients with hypopituitarism: assessment with radionuclide angiography. Eur J Nucl Med 1996;23: 390-394.
21. Colao A, Soma CD, Cuocolo A, et al. Improved cardiovascular risk factors and cardiac performance after 12 months of growth hormone (GH) replacement in young adult patients with GH deficiency. J Clin Endocrinol metab 2001; 86: 1874-1881.
22. Colao A, Soma CD, Pivonello R, et al. The cariovascular risk of adult GH deficiency (GHD) improved after GH replacement and worsened in untreated GHD: a 12 month prospective study. J Clin Endocrinol metab 2002; 87: 10881093.
23. Smit JWA, Janssen YJH, Lamb HJ, et al. Six months of recombinant human GH therapy in patients with ischemic cardiac failure does not influence left ventricular function and mass. J Clin Endocrinol metab 2001; 86: 4638-4643.
24. Nass R, Huber RM, Klaus V, et al. Effect of growth hormone (GH) replacement therapy on physical work capacity and cardiac and pulmonary function in patients with GH deficiency acquired in adulthood. J Clin Endocrinol metab 1995; 80: 552-557.