The GH-IGF-I axis and the cardiovascular system: clinical implications

GH and IGF-I affect cardiac structure and performance. In the general population, low IGF-I has been associated with higher prevalence of ischaemic heart disease and mortality. Both in GH deficiency (GHD) and excess life expectancy has been reported to be reduced because of cardiovascular disease.

To review the role of the GH-IGF-I system on the cardiovascular system.

Recent epidemiological evidence suggests that serum IGF-I levels in the low-normal range are associated with increased risk of acute myocardial infarction, ischaemic heart disease, coronary and carotid artery atherosclerosis and stroke. This confirms previous findings in patients with acromegaly or with GH-deficiency showing cardiovascular impairment. Patients with either childhood- or adulthood-onset GHD have cardiovascular abnormalities such as reduced cardiac mass, diastolic filling and left ventricular response at peak exercise, increased intima-media thickness and endothelial dysfunction. These abnormalities can be reversed, at least partially, after GH replacement therapy. In contrast, in acromegaly chronic GH and IGF-I excess causes a specific cardiomyopathy: concentric cardiac hypertrophy (in more than two-thirds of the patients at diagnosis) associated to diastolic dysfunction is the most common finding. In later stages, impaired systolic function ending in heart failure can occur, if GH/IGF-I excess is not controlled. Abnormalities of cardiac rhythm and of cardiac valves can also occur. Successful control of acromegaly is accompanied by decrease of the left ventricular mass and improvement of cardiac function.

The cardiovascular system is a target organ for GH and IGF-I. Subtle dysfunction in the GH-IGF-I axis are correlated with increased prevalence of ischaemic heart disease. Acromegaly and GHD are associated with several abnormalities of the cardiovascular system and control of GH/IGF-I secretion reverses (or at least stops) cardiovascular abnormalities.