Cortisol, testosterone, and coronary heart disease: prospective evidence from the Caerphilly study.

BACKGROUND: There is a popular belief that chronic stress causes heart disease through psychoneuroendocrine mechanisms. We have examined whether an elevated circulating cortisol-to-testosterone ratio increases the risk of ischemic heart disease. METHODS AND
RESULTS: We undertook 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).
CONCLUSIONS: This is the first population-based prospective study that has found a specific association between cortisol:testosterone ratio and incident ischemic heart disease, apparently mediated through the insulin resistance syndrome. Whether this reflects the effects of chronic stress, behavioral factors, or genetic influences remains to be determined.