High cortisol and low DHEA both predict increased cardiovascular mortality

More evidence for the link between adrenal dysregulation and death from cardiovascular disease is reported in a study recently published in the Journal of Clinical Endocrinology & Metabolism. The authors observe:

"The stress hormone cortisol has been linked with unfavorable cardiovascular risk factors, but longitudinal studies examining whether high levels of cortisol predict cardiovascular mortality are largely absent...The aim of this study was to examine whether urinary cortisol levels predict all-cause and cardiovascular mortality over 6 yr of follow-up in a general population of older persons."

They studied 861 subjects by assessing 24 hour urinary cortisol levels at the beginning, then followed them for 6 years during which they documented death from all causes and death from ischemic and cerebrovascular disease in particular. What did the data show?

"After adjustment for sociodemographics, health indicators, and baseline cardiovascular disease, urinary cortisol did not increase the risk of noncardiovascular mortality, but it did increase cardiovascular mortality risk. Persons in the highest tertile of urinary cortisol had a five times increased risk of dying of cardiovascular disease. This effect was found to be consistent across persons with and without cardiovascular disease at baseline."

Their concluding comments express the robustness of their findings and suggest that circulatory damage may be an important mechanism by which high cortisol is so harmful for the brain:

"High cortisol levels strongly predict cardiovascular death among persons both with and without preexisting cardiovascular disease. The specific link with cardiovascular mortality, and not other causes of mortality, suggests that high cortisol levels might be particularly damaging to the cardiovascular system."

Interestingly, we find another paper just published in the same journal that 'fleshes out' the connection between adrenal dysregulation and death from cardiovascular disease. The authors state:

"The age-related decline in dehydroepiandrosterone (DHEA) levels is thought to be of importance for general and vascular aging...We tested the hypothesis that low serum DHEA and DHEA sulfate (DHEA-S) levels predict all-cause and cardiovascular disease (CVD) death in elderly men."

Both cortisol and DHEA, an important androgen for vitality, body composition, mood and immune regulation, are produced in the adrenal glands. Excessive production of cortisol typically depletes the resources to produce DHEA, a phenomenon call the 'pregnenolone steal'. The authors analyzed baseline levels of DHEA in 2644 Swedish men, then correlated this with mortality data:

"Low levels of DHEA-S predicted death from all causes; but not cancer. Analyses with DHEA gave similar results."

It was particularly interesting to note that...

"The association between low DHEA-S and CVD death remained after adjustment for C-reactive protein and circulating estradiol and testosterone levels. When stratified by the median age of 75.4 yr, the mortality prediction by low DHEA-S was more pronounced among younger  than older men."

The discerning clinician will recognize that for cardiovascular risk assessment to be complete, cortisol and DHEA levels should be evaluated—ideally by salivary hormone collections that delineate the important diurnal cortisol rhythm.