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 abnormal ities in cardiac structure and performance which ultimately determine an in creased cardiovascular morbidity and mortality. OBJECTIVE To investigate whether the age of onset of GHD plays a role in de termining the negative effects on the heart. DESIGN Open cross-sectional PATIENTS 55 patients with adulthood-onset GHD and 36 healthy sex- and age-m atched controls. Patients and controls were divided into 2 groups in line w ith age: 32 patients and 16 controls, were aged less than or equal to 35 ye ars (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 me asurement, plasma IGF-I level assay, and equilibrium radionuclide angiograp hy. RESULTS Plasma IGF-I levels were significantly lower in patients than in co ntrols (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), wh ile 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 pati ents, both resting (P = 0.02) and exercise heart rate (P = 0.01) were signi ficantly lower than in controls. Diastolic filling when measured as end-dia stolic 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 i n 30 patients (54.5%) and 10 controls (27.7%, chi(2) = 5.3, P = 0.02): 17 y oung (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 mid dle-aged patients (P = 0.004). An impaired LVEF at rest (< 50%) was found i n 13 patients (23.6%) and in none of controls (chi(2) = 8.1, P = 0.004). Th e exercise induced changes in LVEF (Delta EF) were significantly lower in b oth patients groups than in age-matched controls (P < 0.0001). Impaired LVE F response to exercise (< 5% increase vs. basal value) was found in 36 pati ents (65.4%) and in 5 controls (13.8%, chi(2) = 21.3, P < 0.000): 21 young (65.6%) and 15 middle-aged patients (65.2%). The peak ejection rate (PER) w as also significantly lower in young GHD patients than in controls (P < 0.0 01). Exercise duration and capacity were significantly reduced in both grou ps of GHD patients. In the patient group, age was significantly correlated with SBP and DBP lev els 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), w ith 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 LVE F at rest (r = - 0.254, P < 0.05). Finally, a significant correlation was f ound 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 lev els 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 w ere the strongest predictor of DBP at peak exercise (t = 2.2, P = 0.03). CONCLUSIONS Diastolic filling abnormalities and impaired left ventricular e jection fraction response at peak exercise were found in the majority of pa tients with GHD acquired in adulthood, regardless of the patients age and a ge of disease onset. On this basis a careful cardiological assessment of GH D adult patients by radionuclide angiography can be helpful in diagnosing e arly stages of cardiac failure which could then be monitored during GH repl acement therapy.