Background

Growth hormone treatment reduces blood pressure and lipid concentrations. We assessed long-term changes in blood pressure, lipid concentrations, and carotid intima media thickness over a 5-year period after cessation of growth hormone treatment in adults born small for gestational age.

Methods

We did a longitudinal observational study at a medical centre in the Netherlands between April 1, 2004, and April 1, 2016. We included adults born small for gestational age who were treated with growth hormone (1 mg/m² per day); treatment started during childhood until adult height. Participants were evaluated at cessation of treatment, and 6 months, 2 years, and 5 years later. We compared cardiovascular risk factors with untreated controls from the PROGRAM study.

Findings

We included 199 participants born small for gestational age and treated with growth hormone along with 285 controls: 51 untreated short adults born small for gestational age, 92 untreated adults born small for gestational age with spontaneous catch-up growth, and 142 adults born appropriate for gestational age. In the 6 months after treatment cessation, systolic blood pressure increased temporarily from 113·00 mm Hg (95% CI 111·18–114·82) to 116·92 mm Hg (115·07 to 118·77; p<0·001) and diastolic blood pressure increased temporarily from 62·19 mm Hg (60·99–63·38) to 66·51 mm Hg (65·14–67·89; p<0·001). At 5 years after treatment cessation, mean systolic blood pressure was 109·2 mm Hg (105·5–113·0) and mean diastolic blood pressure was 63·4 mm Hg (60·9–65·9), similar to the values at cessation. Lipid concentrations were non-significantly higher 5 years after treatment cessation (p values 0·09–0·21) than at treatment cessation. Cessation of growth hormone had no effect on carotid intima media thickness. At 5 years after cessation, total cholesterol was lower in adults treated with growth hormone (mean 4·21 mmol/L, 95% CI 4·04–4·38) than in untreated short adults born small for gestational age (4·66 mmol/L, 4·42–4·92; p=0·0030), as was mean LDL cholesterol (2·28 mmol/L, 2·14–2·43 vs 2·85 mmol/L, 2·62–3·10; p<0·0001); blood pressure and carotid intima media thickness did not differ between these two groups (p values >0·12). At 5 years after cessation, systolic blood pressure, diastolic blood pressure, lipid concentrations, and carotid intima media thickness of adults treated with growth hormone were not different to those in adults born small for gestational age who had spontaneous catch-up growth or adults born appropriate for gestational age.

Interpretation

Long-term growth hormone treatment in children born small for gestational age has no unfavourable effects on cardiovascular health in early adulthood and improves lipid profiles.

Funding

Novo Nordisk (Netherlands).

中文翻译：

---

生长激素治疗停止后胎龄小的年轻人的心血管危险因素和颈动脉内膜中层厚度：一项为期5年的纵向研究

背景

生长激素治疗可降低血压和血脂浓度。我们评估了对于年龄较小的成年婴儿，在停止生长激素治疗后的5年内，血压，脂质浓度和颈动脉内膜中层厚度的长期变化。

方法

我们做了一个纵向观察研究在荷兰一个医疗中心2004年4月1日至2016年4月1日之间，我们谁包括用生长激素（1毫克/立方米处理出生小于胎龄成人²每天）; 治疗始于儿童时期，直至成年身高。在停止治疗以及6个月，2年和5年后对参与者进行评估。我们将心血管危险因素与未经研究的对照组进行了比较。

发现

我们纳入了199名在胎龄以下出生并接受生长激素治疗的参与者以及285名对照：51名未经治疗的矮个成年人出生于胎龄的未成年矮人，92名未经治疗的矮个成年人在妊娠期自发生长的成年个体和142名适龄的成人胎龄。在停止治疗后的6个月中，收缩压暂时从113·00 mm Hg（95％CI 111·18–114·82）上升至116·92 mm Hg（115·07至118·77； p <0· 001）和舒张压暂时升高，从62·19毫米汞柱（60·99-63·38）增至66·51毫米汞柱（65·14-67·89； p <0·001）。停止治疗后5年，平均收缩压为109·2 mm Hg（105·5–113·0），平均舒张压为63·4 mm Hg（60·9–65·9），与停止时的值。停药后5年的血脂浓度无统计学意义（p值0·09-0·21）高于停药。停止生长激素对颈动脉内膜中层厚度没有影响。停止后5年，接受生长激素治疗的成年人（平均4·21 mmol / L，95％CI 4·04–4·38）的总胆固醇比未治疗的胎龄小的矮个成年人的总胆固醇要低（4·66）。 mmol / L，4·42–4·92； p = 0·0030，平均低密度脂蛋白胆固醇（2·28 mmol / L，2·14–2·43vs 2·85 mmol / L，2·62-3·10；p <0·0001）；两组的血压和颈动脉内膜中层厚度无差异（p值> 0·12）。停止生长后5年，接受生长激素治疗的成年人的收缩压，舒张压，血脂浓度和颈动脉内膜中层厚度与那些自发追赶生长的小胎龄成年人或出生的成年人无差异。适合胎龄。

解释

在胎龄小的儿童中长期生长激素治疗不会对成年早期的心血管健康产生不利影响，并会改善血脂状况。

资金

Novo Nordisk（荷兰）。