Does the age of onset of growth hormone deficiency affect cardiac performance? A radionuclide angiography study

BACKGROUND: GH and IGF-I seem to play a relevant role in cardiac development and performance. Long-standing GH deficiency (GHD) causes several abnormalities in cardiac structure and performance which ultimately determine an increased cardiovascular morbidity and mortality. OBJECTIVE: To investigate whether the age of onset of GHD plays a role in determining the negative effects on the heart. DESIGN: Open cross-sectional PATIENTS: 55 patients with adulthood-onset GHD and 36 healthy sex- and age-matched controls. Patients and controls were divided into 2 groups in line with age: 32 patients and 16 controls, were aged </= 35 years (young); while 23 patients and 20 controls were aged between 36 and 60 years (middle-aged). The estimated disease duration was similar in young (6.7 +/- 0.5 years) and middle-aged patients (8.1 +/- 1.2 years, P = 0.2). STUDY PROTOCOL: All subjects underwent ECG, blood pressure and heart rate measurement, plasma IGF-I level assay, and equilibrium radionuclide angiography. RESULTS: Plasma IGF-I levels were significantly lower in patients than in controls (P < 0.0001). When considered as a whole, no difference in systolic (SBP) and diastolic blood pressure (DBP) at peak exercise was found between patients and controls. However, a significant decrease of SBP at rest was found in young patients as compared to age-matched controls (P = 0.009), while a significant increase of DBP at rest was found in middle-aged patients as compared to age-matched controls (P = 0.03). In addition, in young patients, both resting (P = 0.02) and exercise heart rate (P = 0.01) were significantly lower than in controls. Diastolic filling when measured as end-diastolic volume (EVD/sec), was significantly reduced in middle-aged patients (P = 0.04). An impaired peak filling rate (PFR) (< 2.5 EDV/sec) was found in 30 patients (54.5%) and 10 controls (27.7%, chi2 = 5.3, P = 0.02): 17 young (53.1%) and 13 middle-aged patients (56.5%). A significant decrease of left ventricular (LV) ejection fraction (EF) at peak exercise was found in both patients groups (P < 0.0001) while LVEF at rest was lower only in middle-aged patients (P = 0.004). An impaired LVEF at rest (< 50%) was found in 13 patients (23.6%) and in none of controls (chi2 = 8.1, P = 0.004). The exercise induced changes in LVEF (DeltaEF) were significantly lower in both patients groups than in age-matched controls (P < 0.0001). Impaired LVEF response to exercise (< 5% increase vs. basal value) was found in 36 patients (65.4%) and in 5 controls (13.8%, chi2 = 21.3, P < 0.000): 21 young (65.6%) and 15 middle-aged patients (65.2%). The peak ejection rate (PER) was also significantly lower in young GHD patients than in controls (P < 0.001). Exercise duration and capacity were significantly reduced in both groups of GHD patients. In the patient group, age was significantly correlated with SBP and DBP levels both at rest (r = 0.612, and r = 0.516, respectively, P < 0.001) and at peak exercise (r = 0.4, P < 0.005 and r = 0.34, P < 0. 01, respectively), with exercise duration (r = - 0.383, P < 0.005) and capacity (r = - 0.355, P = 0.005). Disease duration was also correlated with IGF-I levels (r = - 0.319, P < 0.01), SBP levels at peak exercise (r = 0.352, P = 0.005), and LVEF at rest (r = - 0.254, P < 0.05). Finally, a significant correlation was found between IGF-I levels and DBP at peak exercise (r = 0.3, P < 0.05) and between GH peak at ARG + GHRH test and LVEF at rest (r = 0.232, P < 0.05). Exercise-induced changes in LVEF were significantly correlated with SBP levels at peak exercise (r = - 0.401, P < 0.005), PFR expressed as EDV/sec (r = - 0.306, P < 0.05) and SV/sec (r = - 0.292, P < 0.05). At multiple regression analysis in the patient group, age was the strongest predictor of SBP both at rest (t = 4.17, P < 0.0001) and at peak exercise (t = 2.32, P = 0.025), and capacity (t = - 2.84, P = 0.007). IGF-I levels were the strongest predictor of DBP at peak exercise.