School of Medicine, Keele University, Stoke-on-Trent, Staffordshire, ST4 7QB, United Kingdom
Correspondence: Address all correspondence and requests for reprints to: R. N. Clayton, M.D., Ph.D., School of Medicine, Keele University, Thornburrow Drive, Stoke-on-Trent, Staffordshire ST4 7QB, United Kingdom. E-mail: r.n.clayton{at}keele.ac.uk
Even with modern treatment, acromegaly is associated with a2- to 3-fold increase in mortality, mainly from vascular disease,which is probably a result of the long exposure of tissues toexcess GH before diagnosis and treatment. There is accumulatingevidence that effective treatment to lower serum GH levels toless than 1–2 ng/ml (glucose suppressed or random, respectively)and normalize IGF-I improves long-term outcome and survival.In addition to recognized cardiovascular risk factors of hypertension,type 2 diabetes mellitus, and dyslipidemia, there is accumulatingevidence of specific structural and functional changes in theheart in acromegaly. Along with endothelial dysfunction, thesechanges may contribute to the increased mortality in this disease.There are specific structural changes in the myocardium withincreased myocyte size and interstitial fibrosis of both ventricles.Left ventricular hypertrophy is common even in young patientswith short duration of disease. Some of these structural changescan be reversed by effective treatment. Functionally, the mainconsequence of these changes is impaired left ventricular diastolicfunction, particularly when exercising, such that exercise toleranceis reduced. Diastolic function improves with treatment, butthe effect on exercise tolerance is more variable, and morelongitudinal data are required to assess the benefits. Whatscant data there are on rhythm changes suggest an increase incomplex ventricular arrhythmias, possibly as a result of thedisordered left ventricular architecture. The functional consequencesof these changes are unclear, but they may provide a usefulearly marker for the ventricular remodeling that occurs in theacromegalic heart. Endothelial dysfunction, especially flow-mediateddilatation, is an early marker of atherosclerosis, and limiteddata imply that this is impaired in active acromegaly and canbe improved with treatment. Similarly, early arterial structuralchanges, such as thickened intima media layer, appear more commonin acromegalics, and there are hints that this may diminishwith effective treatment, although more studies are requiredfor a definite conclusion on this topic. In conclusion, impairedcardiac and endothelial structure and function in acromegalyare risk factors for vascular mortality and should be regardedas legitimate therapeutic targets in the overall managementof this condition.
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