The hypothalamic-pituitary-adrenal axis activity as a predictor of cardiovascular disease, type 2 diabetes and stroke

J Intern Med. 2000 Feb;247(2):188-97. doi: 10.1046/j.1365-2796.2000.00603.x.


Objectives: The hypothalamic-pituitary-adrenal (HPA) axis, the mediator of cortisol, plays a central role in the homeostatic processes. In this study, we addressed the potential impact of HPA axis activity on established anthropometric, metabolic and haemodynamic risk factors for cardiovascular disease (CVD), type 2 diabetes mellitus and stroke.

Design: A cross-sectional study.

Subjects: A subgroup of 284 men from a population sample of 1040 at the age of 51 years.

Main outcome measures: Anthropometric measurements included body mass index (BMI, kg m-2), waist/hip circumference ratio (WHR) and abdominal sagittal diameter (D). Overnight fasting values of blood glucose, serum insulin, triglycerides, total, low (LDL) and high density (HDL) lipoprotein cholesterol, as well as resting heart rate and blood pressure, were also determined. By using repeated diurnal salivary cortisol measurements during everyday conditions, methods were developed to characterize the status of the HPA axis, and set in relation to the anthropometric, metabolic and haemodynamic measurements.

Results: In bivariate analyses, risk factors intercorrelated in clusters of anthropometric (BMI, WHR, D), metabolic (insulin, glucose and their ratio, triglycerides, cholesterol [total and LDL], HDL cholesterol [negative]) and haemodynamic (systolic and diastolic blood pressure and heart rate) measurements. This was also the case in the two-dimensional scaling analysis, where, however, HDL separated out. A normal HPA axis status, characterized by high variability and morning cortisol values, as well as a clear response to a standardized lunch and dexamethasone suppression test, was then introduced by a statistical weighting procedure. This did not essentially change the results of either the bivariate correlation matrix or the two-dimensional scaling analysis. A similar introduction of a pathological HPA axis, characterized by low variability and morning cortisol values, a poor lunch-induced cortisol response and a blunted dexamethasone suppression of cortisol, changed the results markedly. Now strong and consistent correlations were found not only within but also between different clusters of risk factors, which also congregated into one distinct cluster, again except for HDL cholesterol.

Conclusions: These results disclose the prospect of an overriding function of a pathological HPA axis on other, established risk factors for CVD, type 2 diabetes and stroke. Its close association to HPA axis dysfunction may explain the previously reported powerful risk indication of abdominal obesity for the diseases mentioned. The HPA axis abnormality has been reported to be a characteristic consequence of frequently repeated or chronic environmental stress challenges.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue
  • Blood Glucose / metabolism
  • Blood Pressure
  • Body Constitution
  • Body Mass Index
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / physiopathology*
  • Cholesterol / blood
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Heart Rate
  • Humans
  • Hydrocortisone / metabolism
  • Hypothalamo-Hypophyseal System / physiology
  • Hypothalamo-Hypophyseal System / physiopathology*
  • Insulin / blood
  • Male
  • Middle Aged
  • Pituitary-Adrenal System / physiology
  • Pituitary-Adrenal System / physiopathology*
  • Predictive Value of Tests
  • Risk Factors
  • Saliva / metabolism
  • Stroke / blood
  • Stroke / physiopathology*
  • Sweden
  • Triglycerides / blood


  • Blood Glucose
  • Insulin
  • Triglycerides
  • Cholesterol
  • Hydrocortisone