July 20, 2005
Bedrood B.S. and Asher Kimchi M.D.
Bristol, UK- The
contributions of stress to many disease processes have been
studied for many years. While the stressors and physical
symptoms of stress can be subjective, biological markers have
been used to study stress-associated disease. A prospective
cohort study conducted by George Davey Smith, DSc et al from the
University of Bristol in the United Kingdom, compared cortisol
to testosterone ratios to incidence and mortality of ischemic
heart disease (IHD). The study found a specific association
between cortisol:testosterone ratio and incident
ischemic heart disease, apparently mediated through
the insulin resistance syndrome. This study was published in the
July 19, 2005 issue of Circulation.
Neuroendocrine changes have been considered a central component
of stress for many years. Speculation about the biological
effects of stress on disease processes has
particularly focused on glucocorticoids, which can
show long-term elevation in response to chronic stressors.
Glucocorticoids also suppress testosterone levels in men. A high
cortisol to testosterone ratio is a biological indicator of
chronic high stress.
This study was a prospective, cohort study of 2512 men aged 45
to 59 years between 1979 and 1983 from Caerphilly,
South Wales, with a mean follow-up of 16.5 years.
Subjects underwent a clinical examination, and morning
fasting blood samples were taken for analysis of cortisol
levels, testosterone levels, and other cardiovascular
risk factors. The ratio of cortisol to testosterone
showed weak associations with potential confounding
factors but strong positive associations with
components of the insulin resistance syndrome (P<0.001).
A positive linear trend was seen across quintiles of
cortisol:testosterone ratio for incident ischemic
heart disease (age-adjusted OR per z score
change in ratio 1.22, 95% CI 1.07 to 1.38, P=0.003).
This was markedly attenuated after adjustment for
components of the insulin resistance syndrome
(age-adjusted OR per z score change in ratio
1.10, 95% CI 0.96 to 1.25, P=0.18). There was
no association between the cortisol:testosterone ratio and other
causes of death (age-adjusted hazard ratio 0.99, 95% CI
0.88 to 1.11, P=0.81).
In this prospective study, C/T ratio was positively associated
with IHD mortality and incidence. Adjustment for potential
socioeconomic and behavioral confounding variables
had little influence on these associations, but they
appeared to be mediated by components of the insulin
resistance syndrome (elevated blood pressure,
triglyceride levels, body mass index, total cholesterol, HDL
cholesterol, and impaired glucose tolerance). This
suggests that methods of reducing the C/T ratio may
improve insulin resistance and reduce the risk of CHD.
Co-authors: George Davey Smith, DSc; Yoav Ben-Shlomo, BSc, MBBS,
MRCP, FFPHM, PhD; Andrew Beswick, BSc; John Yarnell, MBChB, DPH,
MSCM, MD, MFPHM (Ire), FFPHM; Stafford Lightman, MBChB, PhD,
FMedSci; Peter Elwood, DSc, MD, FRCP, FFPHM