title: Hypothalamic-pituitary-adrenal axis activity under resting conditions and cardiovascular risk factors in adolescents.
abstract: BACKGROUND
  Activation of the hypothalamic-pituitary-adrenal (HPA) axis has been associated with higher levels of cardiovascular (CVD) risk factors in adults. This study aimed to assess the relation between measures of HPA axis activity under resting conditions and CVD risk factors in a general population of adolescents at 17 years.
  
  
  METHODS
  A total of 1134 adolescents from the Western Australian Pregnancy Cohort (Raine) Study had phenotypic and socio-demographic data. The associations between HPA axis measures (plasma ACTH, total cortisol, calculated free cortisol, corticosteroid binding globulin (CBG), and salivary cortisol) and a range of cardiovascular risk factors were examined using multivariable linear regression models, with adjustment for gender, adiposity, birth weight, gestational age, and socio-behavioural factors.
  
  
  RESULTS
  Plasma total cortisol was positively associated with systolic blood pressure (SBP) (p=0.011), total cholesterol, HDL-cholesterol, and triglycerides (all p<0.001), and hs-CRP (p=0.047). Salivary cortisol was associated positively with HDL-C (p=0.033) and negatively with LDL-cholesterol (p=0.016); plasma calculated free cortisol was positively associated with triglycerides (p=0.006); plasma CBG was positively associated with total cholesterol and HDL-cholesterol (both p<0.001), LDL-cholesterol (p=0.022), and hs-CRP (p=0.001). After correction for multiple comparisons, significant associations remained for total cortisol with total cholesterol, HDL-C, and triglycerides; for calculated free cortisol with triglycerides; and for CBG with HDL-C, total cholesterol, and hs-CRP. Plasma ACTH was not associated with any cardiovascular risk factor. There was no association between BMI and any measure of HPA axis activity.
  
  
  CONCLUSIONS
  In an adolescent population, HPA axis measures under resting conditions are associated with a range of CVD risk factors. Clarification of the mechanisms underlying these associations in adolescence would be an important step in understanding the evolution of adult CVD.
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Australia. Electronic address: cleha@meddent.uwa.edu.au.
authors.forename: Chi
authors.initials: C
authors.lastname: Le-Ha
authors.affiliation: School of Women's and Infant's Health, University of Western Australia.
authors.forename: Carly E
authors.initials: CE
authors.lastname: Herbison
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Australia.
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Beilin
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Australia.
authors.forename: Sally
authors.initials: S
authors.lastname: Burrows
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Australia; Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Australia.
authors.forename: David E
authors.initials: DE
authors.lastname: Henley
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lye
authors.affiliation: Department of Physiology, University of Toronto, Canada.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Matthews
authors.affiliation: School of Women's and Infant's Health, University of Western Australia.
authors.forename: Craig E
authors.initials: CE
authors.lastname: Pennell
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Australia.
authors.forename: Trevor A
authors.initials: TA
authors.lastname: Mori
mesh_terms: D000293:Adolescent; D001481:Basal Metabolism / Q000502:physiology; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D008297:Male; D010913:Pituitary-Adrenal System / Q000502:physiology* / Q000503:physiopathology*; D012146:Rest / Q000502:physiology*; D012307:Risk Factors; D012959:Socioeconomic Factors; D014904:Western Australia / Q000453:epidemiology
keywords: Adolescence; Cardiovascular risk factors; Corticosteroid binding globulin; Cortisol; HPA axis activity