Endocrine Abstracts

Recent epidemiological evidence suggests that low-normal levels of serum IGF-I are associated with increased risk of acute myocardial infarction, ischemic heart disease, coronary and carotid artery atherosclerosis.

The IGF-I system is involved in the regulation of cardiovascular physiopathology: it has a physiological role in regulating glucose, protein and lipid metabolism, and in promoting proliferation, differentiation and migration of many cell types. GH and IGF-I receptors are expressed in cardiomyocytes and in endothelial cells; IGF-I immunoreactivity is reportedly increased in the inner layers of the left ventricle, where both tension and wall stress are high, and gradually decreases towards the epicardial surface. The IGF-I system displays direct effects on atherosclerosis: IGF-I stimulates vascular smooth muscle and endothelial cell proliferation, matrix synthesis, migration of monocytes into the arterial wall, uptake of modified LDL and release of proinflammatory cytokines by macrophages.

Patients with either childhood or adulthood-onset GH deficiency have reduced cardiac mass, impaired diastolic filling and reduced left ventricular response at peak exercise, increased intima-media thickness and endothelial dysfunction. All these abnormalities can be reversed, at least partially, after GH replacement therapy. On the opposite, the chronic excess of GH and IGF-I in acromegaly leads to develop a specific cardiomyopathy. Concentric cardiac hypertrophy occurs in more than two thirds of the patients at diagnosis and is commonly associated to diastolic dysfunction. In later stages, impaired systolic function ending in heart failure can occur, if GH/IGF-I excess is not controlled. Additionally, the acromegalic cardiomyopathy is complicated with abnormalities of cardiac rhythm and of cardiac valves. Successful control of acromegaly is accompanied by decrease of left ventricular mass and improvement of cardiac function. Ageing and long disease duration are negative predictors of severity of the acromegalic cardiomyopathy.