Oral Presentation ESA-SRB-AOTA 2019

Effect of variability in hypothalamic-pituitary-adrenal axis activity on vascular function, insulin sensitivity and lipids (#239)

Anjana Radhakutty 1 2 3 , Tien Lee 1 3 , Brenda Mangelsdorf 1 , Sophie Drake 1 , Morton Burt 1 3
  1. Southern Adelaide Diabetes and Endocrine Services, Repatriation General Hospital, Adelaide, SA, Australia
  2. Endocrinology, Lyell McEwin Hospital, Adelaide, SA, Australia
  3. School of Medicine, Flinders University, Adelaide, SA, Australia

Background: Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis with resultant cortisol hypersecretion in response to stress has been proposed to underlie an association between low birth weight and increased cardiovascular disease. However, the mechanisms underlying this association are not fully clarified. As glucocorticoid therapy can cause vascular dysfunction, insulin resistance and dyslipidaemia we have investigated whether HPA hyperactivity affects these variables.

Methods: Thirty healthy adults (age = 63±8 years, BMI = 25±4 kg/m2) were studied. Serum cortisol 30 minutes after 1 µg Synacthen (ACTH1-24, Novartis Pharmaceuticals, Australia) was used to define HPA activity. Subjects with a cortisol above (n=15) and below (n=15) the median were categorized as high responders and low responders respectively. Reactive hyperaemia index (RHI) was measured by peripheral arterial tonometry to measure endothelial function and augmentation index (AIx) by applanation tonometry to quantify arterial stiffness. Lipids were measured on a fasting blood sample and the Matsuda index was calculated from glucose and insulin concentrations collected fasting and 30 minutely for two hours after a mixed meal (10 kcal/kg, 45% carbohydrate, 15% protein, 40% fat) to estimate insulin sensitivity. Analyses were corrected for age, sex and smoking status using analysis of covariance.

Results: High responders had a lower RHI than low responders (2.1±0.2 vs 2.6±0.2, p=0.04) indicative of worse endothelial function. High responders had a higher AIx than low responders that approached statistical significance (26.3±1.4 vs 22.6±1.4 %, p=0.08) suggesting greater arterial stiffness. Age (p=0.02) and sex (p<0.001) were also independent predictors of AIx. There were no significant differences in LDL cholesterol (2.7±0.3 vs 3.0±0.3 mmol/L, p=0.47), triglycerides (1.2±0.3 vs 1.0±0.3 mmol/L, p=0.66) or Matsuda index (15.9±4.4 vs 21.8±4.4, p=0.73) between high and low responders.

Conclusion: Endothelial dysfunction and increased arterial stiffness are likely to contribute to the association between HPA hyperactivity and an increased risk of cardiovascular disease.