Untreated GH deficient (GHD) adults have shown increased cardiovascular morbidity and mortality, increased atherosclerotic plaques, and increased intima-media thickness of carotid arteries. Along with the altered body composition of GHD adults, changes in lipid profile, insulin resistance and lowered exercise capacity, this leads to a high cardiovascular risk for such patients. Pregnancy-associated plasma protein-A (PAPP-A) has been proposed as a marker of an increased risk of atherothrombotic events in general, with levels correlating with carotid intima-media thickness, an early indicator of cardiovascular events.
Joaquim et al conducted a clinical study on 14 GHD adults in whom levels of PAPP-A, leptin, fibrinogen and high-sensitive C-reactive protein (hsCRP) were measured at baseline and after 1 year of GH replacement therapy. The study found that at baseline GHD adults had higher PAPP-A, leptin, fibrinogen and hsCRP levels than controls. GH therapy was shown to decrease levels of PAPP-A and fibrinogen, while leptin and adiponectin levels showed no change. The fourteen adult onset GHD patients were assessed and matched with 28 healthy control subjects, for age, sex, body mass index and menopausal status. Blood samples were taken after an overnight fast, centrifuged, and analysed for a number of constituents including, PAPP-A leptin, fibrinogen and hsCRP using appropriate assays for each.
The study concluded that PAPP-A serum concentrations were higher in GHD patients than in matched controls and that GH therapy lowered PAPP-A levels. Although the study used a small number of patients, it is the first to study PAPP-A levels in GHD adults and represents a novel finding. The authors speculate that GH therapy may reverse early onset atherosclerosis and decrease the cardiovascular risk in these patients. It is recommended that further and larger studies are required to determine whether the decrease in PAPP-A levels as observed in this study does lead to a reduction in cardiovascular events in GHD patients.
Joaquin, C., Aguilera, E., Granada, M.L., Pastor, M.C., Salinas, I., Alonso, N., Sanmartí, A. European Journal of Endocrinology, 158, 483-490.
DOI: 10.1530/EJE-07-0554