Effects of growth hormone on cardiovascular risk factors and atherosclerosis

Abstract

Hypopituitary patients with growth hormone (GH) deficiency (GHD) have increasedmorbidity and mortality from cardiovascular disease (CVD). GH treatment has both beneficialand potentially negative cardiovascular effects. The mechanism for the dyslipidemia observedin these patients is not completely understood and animal experiments indicate that GH isimportant for dietary effects on serum cholesterol. The aim was to investigate effects of GHon diet-induced changes in serum cholesterol and on other cardiovascular risk factors andatherosclerosis.Effects of GH on cholesterol metabolism were evaluated in a cross-over study of sixGHD patients during a high-fat and high-cholesterol 17-day diet with and without GHtreatment. GH attenuated the increase in cholesterol biosynthesis induced by the high-fat diet,probably due to maintained LDL receptor activity. In contrast to animal studies, GH did notinfluence serum LDL cholesterol levels during fat feeding in humans.Effects of GH on cardiovascular risk factors in relation to atherosclerosis were studiedin 34 cardiovascularly healthy hypopituitary patients with GHD, in an open prospective 3-year trial. Results were compared with two healthy control groups matched for age, sex andsmoking. Hypopituitary patients with GHD had higher waist-to-hip ratio, resting heart rate,fasting insulin levels, interleukin-6 (IL-6) concentrations and tissue plasminogen activatorantigen levels together with lipid disturbances including higher serum triglycerides, lowerHDL cholesterol and smaller LDL particles than both the BMI-matched and the non-obesecontrol group. Patients had higher intima-media thickness (IMT) of the carotid bulb (IMTCAB)than non-obese controls at baseline. Female patients had a more pronouncedcardiovascular risk profile compared to their BMI-matched controls. IMT of the commoncarotid artery (CCA) correlated to serum IL-6 levels at baseline in the patient group.Independent risk factors for high IMT-CAB were age and pituitary disease in the total cohort.The waist circumference and CRP levels decreased but insulin resistance increased inpatients after GH treatment. The IMT-CAB increased during three years in both controlgroups, but was unchanged in GH-treated patients. The IMT-CCA was unchanged in all threegroups. The change in IMT-CCA was independently correlated to the change in serum tumournecrosis factor-á in the patient group, but none of the measured variables correlatedindependently to the change in IMT-CAB.In conclusion, we found that GH attenuated the increased cholesterol synthesis inducedby fat feeding, but GH did not influence the increase in serum LDL cholesterol during diet.Pituitary-deficient GHD patients without manifest CVD demonstrated several cardiovascularrisk factors compared to controls independent of their BMI and female patients were at higherrisk. Despite this high risk pattern, GH treatment in GHD patients reduced the rate ofprogression of atherosclerosis in the CAB. The atherosclerosis progression rate in CCA wassimilar in patients to that observed in healthy BMI-matched as well as non-obese controls.