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Summary

BACKGROUND GH and IGF-I seem to play a relevant role in cardiac development and performance. Longstanding 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%, x2= 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 (x2= 8.1, P= 0.004). The exercise Induced changes in LVEF (ΔEF) 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%, x2= 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=0.405). 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 SEP 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(t=2.2, P=0.03).

CONCLUSIONS Diastolic filling abnormallties and impaired left ventricular ejection fraction response at peak exercise were found In the majority of patients with GHD acquired In adulthood, regardless of the patients age and age of disease onset. On this bask a careful cardiological assessment of GHD adult patients by radionuclide anglography can be helpful in diagnosing early stages of cardiac failure which could then be monitored during GH replacement therapy.