title: The effects of depot long-acting somatostatin analog on central aortic pressure and arterial stiffness in acromegaly.
abstract: Acromegaly is associated with increased cardiovascular risk. Although conventional risk factors such as glucose intolerance, hypertension, and dyslipidemia probably contribute, there may also be direct effects of GH/IGF-I excess on the vasculature. To study the effects of GH excess on the vasculature, we have assessed arterial stiffness in acromegalic subjects with and without active disease and have investigated the effects of Sandostatin LAR (OCT-LAR) on vascular function. Sixteen normotensive subjects with acromegaly (10 males and 6 females) and 8 healthy controls were studied. Of the acromegalic subjects, eight had active disease (group A), and eight were cured (GH < 2.5 mU/liter; group B). The three groups were age, sex, and blood pressure matched. Group A subjects were restudied after 3 and 6 months of OCT-LAR therapy. Arterial stiffness was assessed by analyzing central arterial pressure waveforms derived from measured radial artery waveforms. This allowed determination of the augmentation of central pressure and the augmentation index. Lipids, glucose, and IGF-I were also measured. Comparing the three groups (ANOVA; mean +/- SD), the augmentation index was higher in group A (28 +/- 12 vs. 12 +/- 13%; P < 0.01) but not in group B (22 +/- 7 vs. 12 +/- 13%; P = 0.60), compared with controls. IGF-I was higher in group A (50.3 +/- 21.2 nmol/liter; P < 0.01), compared with group B (22.5 +/- 8.9 nmol/liter) and controls (19.5 +/- 5.3 nmol/liter). On regression analysis, IGF-I concentration was identified as a strong independent predictor of the augmentation index (beta = 0.50; P = 0.007). There were no significant differences in aortic systolic pressure, aortic diastolic pressure, lipids, or glucose. Compared with baseline, OCT-LAR treatment resulted in a lowering of augmentation index at 3 months (20 +/- 15 vs. 28 +/- 12%; P < 0.05), but at 6 months (24 +/- 16%; P = 0.21) there was no significant change. IGF-I was reduced from 50.3 +/- 21.2 nmol/liter at baseline to 31.4 +/- 13.2 nmol/liter at 3 months (P < 0.05) and 26.6 +/- 15.8 nmol/liter at 6 months (P < 0.05). In conclusion, acromegaly is associated with changes in the central arterial pressure waveform, suggesting large artery stiffening. This may have important implications for cardiac morphology and performance in acromegaly as well as increasing the susceptibility to atheromatous disease. Large artery stiffness is reduced in cured acromegaly and partially reversed after pharmacological treatment of active disease.
authors.affiliation: Department of Medicine, University Hospital of Wales, Cardiff, CF4 4XN, Wales, United Kingdom. jamie.smith@virgin.net
authors.forename: J C
authors.initials: JC
authors.lastname: Smith
authors.forename: H
authors.initials: H
authors.lastname: Lane
authors.forename: N
authors.initials: N
authors.lastname: Davies
authors.forename: L M
authors.initials: LM
authors.lastname: Evans
authors.forename: J
authors.initials: J
authors.lastname: Cockcroft
authors.forename: M F
authors.initials: MF
authors.lastname: Scanlon
authors.forename: J S
authors.initials: JS
authors.lastname: Davies
mesh_terms: D000172:Acromegaly / Q000188:drug therapy* / Q000503:physiopathology*; D000368:Aged; D001011:Aorta / Q000187:drug effects* / Q000503:physiopathology; D001158:Arteries / Q000187:drug effects* / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects*; D016022:Case-Control Studies; D003692:Delayed-Action Preparations; D004548:Elasticity; D005260:Female; D006728:Hormones / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D003692:Delayed-Action Preparations; D006728:Hormones; D015282:Octreotide