Reduced CV risk with long-term GH replacement in AGHD: data from two large observational studies

Abstract

Adult growth hormone deficiency (AGHD) is associated with an increased risk of cardiovascular (CV) disease. Long-term growth hormone (GH) treatment could improve CV outcomes. The objective of this study was to evaluate CV disease risk in patients with AGHD who received GH replacement therapy for up to 10 years as part of NordiNet® IOS (NCT00960128) and the ANSWER Program (NCT01009905). The studies were observational, non-interventional and multicentre, monitoring long-term effectiveness and safety of GH treatment. NordiNet® IOS involved 23 countries (469 sites) across Europe and the Middle East. The ANSWER Program was conducted in the USA (207 sites). This analysis included patients aged 18-75 years who were GH naïve at study entry, who had ≤10 years of GH treatment data and who could be assessed for CV risk for at least 1 follow-up year. The main outcome measure was risk of CV disease by age 75 years, as calculated with the Multinational Cardiovascular Risk Consortium model (Brunner score) using non-high-density lipoprotein cholesterol adjusted for age, sex and CV risk factors. The results of this analysis showed that CV risk decreased gradually over the 10-year period for GH-treated patients. The risk was lower for patients treated for 2 and 7 years vs age- and sex-matched control groups (not yet started treatment) (14.51% vs 16.15%; P = 0.0105 and 13.53% vs 16.81%; P = 0.0001, respectively). This suggests that GH treatment in people with AGHD may reduce the risk of CV disease by age 75 years compared with matched controls.

Keywords: ANSWER; NordiNet; cardiovascular risk; growth hormone; norditropin.

Figure 1

Study design. At each follow-up year, GH-treated patients were compared to age- and sex-matched untreated patients from the control group (taken from baseline). GH, growth hormone; IOS, International Outcome Study.

Figure 2

Cross-sectional comparison of IGF-I SDS between GH-treated patients at a follow-up year vs matched (age and sex) control groups. Shown are the mean (noughts/crosses within the box), median (dash within the box), 25th/75th percentiles (box) and maximum overserved values (noughts and crosses above the box). GH, growth hormone; IGF-I, insulin-like growth factor-I; SDS, standard deviation score.

Figure 3

Cross-sectional comparison of Brunner score between GH-treated patients at a follow-up year vs matched (age and sex) control groups. Shown are the mean (noughts/crosses within the box), median (dash within the box), 25th/75th percentiles (box) and maximum overserved values (noughts and crosses above the box). GH, growth hormone.

Figure 4

The mean (95% CI) Brunner scores of GH-treated patients and matched control groups at Year 2 and Year 7. Statistical comparisons between GH-treated and matched control patients were assessed using a Welch–Satterthwaite t-test due to unequal variances (Year 2: P = 0.0105; Year 7: P = 0.0001). CI, confidence interval; GH, growth hormone.

Figure 5

Cross-sectional and longitudinal Brunner scores of GH-treated male and female patients. (A) Mean scores and (B) absolute change from baseline. Data are mean ± s.d. GH, growth hormone.

Figure 6

Non-HDL category (mmol/L) for GH-treated patients by follow-up year. (A) All patients, (B) females and (C) males. GH, growth hormone; HDL, high-density lipoprotein.