Abnormal heart rate variability in adults with growth hormone deficiency.

GH-deficient (GHD) patients have increased risk of cardiovascular death and may have cardiac structural abnormalities. In non-GHD patients these are associated with cardiac autonomic dysfunction, and it is possible that autonomic dysfunction is also present in GHD patients. Power spectral analysis (PSA) of heart rate variability (HRV) indirectly measures cardiac autonomic tone and generates peaks at 3 frequency bands, very low frequency (VLF), low frequency (LF) and high frequency (HF). The area under the LF curve is considered to reflect predominantly cardiac sympathetic activity, whereas HF indicates parasympathetic activity. PSA of HRV was performed in 14 normotensive GHD patients (5 men and 9 women; mean age, 35.2 yr) and 19 healthy controls (9 men and 10 women; mean age, 38.3 yr). GHD patients had 26% lower normalized LF power (P < 0.004), 39% higher normalized HF power (P < 0.001), 28% lower normalized VLF power (P < 0.046), and 51% lower LF/HF ratio (an index of sympathovagal balance; P < 0.001) compared to controls. These data indicate that heart rate variability is abnormal in patients with GHD. The decreased sympathetic tone could be a consequence of reduced central sympathetic tone or altered cardiac responsiveness to autonomic control and may contribute to the increased cardiovascular risk in GHD patients.

[1]  R Colombo,et al.  Chemoreceptor dependence of very low frequency rhythms in advanced chronic heart failure. , 1997, The American journal of physiology.

[2]  P. Armstrong,et al.  Heart rate variability assessment early after acute myocardial infarction. Pathophysiological and prognostic correlates. GUSTO ECG Substudy Investigators. Global Utilization of Streptokinase and TPA for Occluded Arteries. , 1996, Circulation.

[3]  D. Hoyt,et al.  Spectral analysis of heart rate variability in the ICU: a measure of autonomic function. , 1996, The Journal of surgical research.

[4]  J. Fleiss,et al.  Frequency Domain Measures of Heart Period Variability and Mortality After Myocardial Infarction , 1992, Circulation.

[5]  A. Mark,et al.  Intracerebroventricular insulin produces nonuniform regional increases in sympathetic nerve activity. , 1994, The American journal of physiology.

[6]  E. Christ,et al.  Dyslipidaemia in Adult Growth Hormone (GH) Deficiency and the Effect of GH Replacement Therapy: A Review , 1998, Trends in Endocrinology & Metabolism.

[7]  B. Biondi,et al.  Growth hormone and heart performance. A novel mechanism of cardiac wall stress regulation in humans. , 1997, European heart journal.

[8]  Dmitry Mironov,et al.  Heart Rate Variability Assessment Early After Acute Myocardial Infarction , 1996 .

[9]  R. Valcavi,et al.  Cardiac performance and mass in adults with hypopituitarism: effects of one year of growth hormone treatment. , 1995, The Journal of clinical endocrinology and metabolism.

[10]  D. Johnston,et al.  Myocardial dysfunction in treated adult hypopituitarism: a possible explanation for increased cardiovascular mortality. , 1992, British heart journal.

[11]  A. Malliani,et al.  Physiology and clinical implications of variability of cardiovascular parameters with focus on heart rate and blood pressure. , 1994, The American journal of cardiology.

[12]  D. Ewing,et al.  The Value of Cardiovascular Autonomic Function Tests: 10 Years Experience in Diabetes , 1985, Diabetes Care.

[13]  Dissociation between microneurographic and heart rate variability estimates of sympathetic tone in normal subjects and patients with heart failure. , 1999 .

[14]  B. Biondi,et al.  A preliminary study of growth hormone in the treatment of dilated cardiomyopathy. , 1996, The New England journal of medicine.

[15]  D L Eckberg,et al.  Mechanisms underlying very-low-frequency RR-interval oscillations in humans. , 1998, Circulation.

[16]  J. Fleiss,et al.  Frequency domain measures of heart period variability to assess risk late after myocardial infarction. , 1993, Journal of the American College of Cardiology.

[17]  A. Rahim,et al.  The assessment of growth hormone status in normal young adult males using a variety of provocative agents , 1996, Clinical endocrinology.

[18]  B. Bengtsson,et al.  Altered lipid pattern explains increased cardiovascular mortality in hypopituitary patients with growth hormone deficiency , 1998, Clinical endocrinology.

[19]  G. Casolo,et al.  Heart rate variability and functional severity of congestive heart failure secondary to coronary artery disease. , 1995, European heart journal.

[20]  K. Caidahl,et al.  Long‐term cardiovascular effects of growth hormone treatment in GH‐deficient adults Preliminary data in a small group of patients , 1996, Clinical endocrinology.

[21]  M. Lesh,et al.  Autonomic nervous system and sudden cardiac death. , 1996, Journal of the American College of Cardiology.

[22]  A. Weetman,et al.  Comparison of the diagnostic utility of the simplified and standard i.m. glucagon stimulation test (IMGST) , 1998, Clinical endocrinology.

[23]  M. Salvatore,et al.  Left ventricular function in young adults with childhood and adulthood onset growth hormone deficiency , 1998, Clinical endocrinology.

[24]  R. Clark,et al.  Growth hormone improves cardiac performance in experimental heart failure. , 1995, Circulation.

[25]  B. Kristensen,et al.  Short and long‐term cardiovascular effects of growth hormone therapy in growth hormone deficient adults , 1994, Clinical endocrinology.

[26]  T. Hedner,et al.  Growth hormone improves cardiac function in rats with experimental myocardial infarction , 1997, European journal of clinical investigation.

[27]  M G Kienzle,et al.  Clinical, hemodynamic and sympathetic neural correlates of heart rate variability in congestive heart failure. , 1992, The American journal of cardiology.

[28]  E. Ghigo,et al.  Consensus guidelines for the diagnosis and treatment of adults with growth hormone deficiency: summary statement of the Growth Hormone Research Society Workshop on Adult Growth Hormone Deficiency. , 1998, The Journal of clinical endocrinology and metabolism.

[29]  E. Benarroch The central autonomic network: functional organization, dysfunction, and perspective. , 1993, Mayo Clinic proceedings.

[30]  M. Elam,et al.  Intense sympathetic nerve activity in adults with hypopituitarism and untreated growth hormone deficiency. , 1998, The Journal of clinical endocrinology and metabolism.

[31]  L. Saccá,et al.  Cardiac structural and functional abnormalities in adult patients with growth hormone deficiency. , 1993, The Journal of clinical endocrinology and metabolism.

[32]  P. Marzullo,et al.  Growth hormone and the heart , 2001, Endocrine Updates.

[33]  L. Mathews,et al.  Regulation of rat growth hormone receptor gene expression. , 1989, The Journal of biological chemistry.

[34]  L. Hagmar,et al.  Increased cerebrovascular mortality in patients with hypopituitarism , 1997, Clinical endocrinology.

[35]  A. Malliani,et al.  Heart rate variability. Standards of measurement, physiological interpretation, and clinical use , 1996 .

[36]  R. Cohen,et al.  Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. , 1981, Science.

[37]  M Pagani,et al.  Absence of low-frequency variability of sympathetic nerve activity in severe heart failure. , 1997, Circulation.

[38]  C. Carella,et al.  Body composition, bone metabolism, and heart structure and function in growth hormone (GH)-deficient adults before and after GH replacement therapy at low doses. , 1993, The Journal of clinical endocrinology and metabolism.

[39]  L. Saccá,et al.  Impaired cardiac performance in GH-deficient adults and its improvement after GH replacement. , 1994, The American journal of physiology.

[40]  G. Sundkvist,et al.  Respiratory influence on heart rate in diabetes mellitus. , 1979, British medical journal.

[41]  C. Wiles,et al.  Growth hormone treatment in growth hormone-deficient adults. I. Effects on muscle mass and strength. , 1991, Journal of applied physiology.

[42]  A. Porta,et al.  Relationship between spectral components of cardiovascular variabilities and direct measures of muscle sympathetic nerve activity in humans. , 1997, Circulation.

[43]  A. Mark,et al.  Mechanisms of insulin action on sympathetic nerve activity. , 1995, Clinical and experimental hypertension.

[44]  O. Kjellgren,et al.  Heart rate variability and baroreflex sensitivity in myocardial infarction. , 1993, American heart journal.

[45]  B. Bengtsson,et al.  Premature mortality due to cardiovascular disease in hypopituitarism , 1990, The Lancet.

[46]  L. Fleisher,et al.  Thermoregulation and heart rate variability. , 1996, Clinical science.

[47]  R Colombo,et al.  Augmented peripheral chemosensitivity as a potential input to baroreflex impairment and autonomic imbalance in chronic heart failure. , 1997, Circulation.

[48]  F. Alford,et al.  1 Growth hormone deficiency and cardiovascular risk , 1998 .

[49]  F. Lombardi,et al.  Heart rate variability and cardiac failure , 1998, Heart.

[50]  S. Lamberts,et al.  The effect of growth hormone administration in growth hormone deficient adults on bone, protein, carbohydrate and lipid homeostasis, as well as on body composition , 1992, Clinical endocrinology.