Observational study finds higher adrenal volume index linked to cortisol and heart failure risk — Evidence Review
Published by researchers at Johns Hopkins University School of Medicine
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Table of Contents
Researchers have developed an AI tool that uses chest CT scans to identify adrenal gland enlargement as a visible biomarker of chronic stress, linking it to increased cortisol exposure and heightened heart failure risk. Related studies broadly support these findings, consistently showing that cortisol levels correlate with cardiovascular risk and that chronic stress has measurable impacts on health, as highlighted by the original study source.
- Multiple studies have established that elevated cortisol, a key hormone involved in stress responses, independently predicts higher mortality and cardiovascular event risks in patients with heart failure and other at-risk populations 1 2 3 4 5.
- The new study's identification of adrenal gland volume as a visible, quantifiable imaging biomarker of chronic stress extends previous research by offering a practical approach to stress measurement, whereas earlier work relied primarily on biochemical assays or questionnaires 1 2 3 4 5.
- Related literature emphasizes the causal relationship between chronic stress, elevated cortisol, and negative cardiovascular outcomes, providing a strong foundation for the clinical value of imaging-based biomarkers in risk stratification and preventive care 1 2 3 4.
Study Overview and Key Findings
Chronic stress has long been recognized as a contributor to a wide range of health issues, yet direct, objective measurement of its cumulative impact within the body has remained a challenge. This study introduces a novel approach: by applying a deep learning AI model to routine chest CT scans, researchers automatically quantified adrenal gland size, proposing it as a biomarker reflecting the biological burden of chronic stress. The significance of this work lies in its use of existing clinical imaging, allowing for large-scale, non-invasive assessment of stress-related health risks—particularly in relation to heart disease. Importantly, the study leverages a unique multi-ethnic cohort integrating imaging, biochemical, and psychosocial data, enabling rigorous evaluation of the new biomarker's clinical relevance.
| Property | Value |
|---|---|
| Organization | Johns Hopkins University School of Medicine |
| Authors | Elena Ghotbi, Shadpour Demehri, Roham Hadidchi, Seyedhouman Seyedekrami, Quincy A. Hathaway, Michael Bancks, Nikhil Subhas, Matthew J. Budoff, David A. Bluemke, R. Graham Barr, Joao A.C. Lima |
| Population | Participants in a multi-ethnic study of atherosclerosis |
| Sample Size | n=2842 |
| Methods | Observational Study |
| Outcome | Adrenal Volume Index, cortisol levels, allostatic load, cardiovascular events |
| Results | Higher AVI linked to greater cortisol exposure and increased heart failure risk. |
Literature Review: Related Studies
To contextualize these findings, we searched the Consensus paper database, which includes over 200 million research papers. The following search queries were used to identify relevant literature:
- AI CT scans stress detection
- cortisol heart failure risk factors
- AVI cortisol exposure health outcomes
| Topic | Key Findings |
|---|---|
| How does cortisol relate to cardiovascular and heart failure risk? | - Elevated serum and salivary cortisol independently predict increased mortality and cardiac event risk in patients with chronic or systolic heart failure 1 2 5. - Higher cortisol is associated with greater prevalence of ischemic heart disease and adverse cardiovascular outcomes, independently of traditional risk factors 3 4. |
| What are the mechanisms linking chronic stress, cortisol, and health outcomes? | - Chronic stress activates the hypothalamic-pituitary-adrenal (HPA) axis, increasing cortisol production, which is linked to metabolic syndrome features and cardiovascular disease 3 4. - Both cortisol and aldosterone levels contribute incrementally and complementarily to mortality risk in heart failure 1 2. |
| Can imaging or novel biomarkers improve chronic stress assessment and clinical practice? | - Traditional methods to assess chronic stress rely on biochemical markers or questionnaires; imaging-based biomarkers like adrenal gland volume offer a practical alternative for large-scale, objective assessments [Original Study]. - New imaging markers must demonstrate predictive value equivalent to or greater than established biochemical markers 1 2 3 4 5. |
How does cortisol relate to cardiovascular and heart failure risk?
Existing research consistently demonstrates a strong association between elevated cortisol levels and increased risk of mortality and adverse cardiac events in patients with heart failure and other cardiovascular conditions. The new study's finding that higher adrenal gland volume (as measured by AI) aligns with greater cortisol exposure and predicts heart failure risk is in line with this established body of evidence.
- Higher serum cortisol and aldosterone are independent predictors of mortality in chronic heart failure, with combined elevation conferring the greatest risk 1.
- Serum cortisol levels, when elevated, predict cardiac events and mortality in heart failure patients, especially in combination with markers of oxidative stress 2.
- Elevated fasting plasma cortisol is linked with greater prevalence of ischemic heart disease, independent of other risk factors 3.
- Meta-analyses and Mendelian randomization studies support a causal relationship between high morning cortisol and incident cardiovascular disease 4.
- High evening salivary cortisol independently predicts mortality in systolic heart failure, suggesting the timing and chronicity of cortisol elevation are relevant 5.
What are the mechanisms linking chronic stress, cortisol, and health outcomes?
The biological effects of chronic stress are mediated through the hypothalamic-pituitary-adrenal (HPA) axis, resulting in sustained cortisol production. Multiple studies highlight that this chronic activation leads to metabolic disturbances and cardiovascular disease risk, with both cortisol and aldosterone contributing to adverse outcomes.
- Chronic HPA axis activation, reflected in persistent cortisol elevation, underlies metabolic syndrome and is associated with ischemic heart disease 3.
- Both cortisol and aldosterone additively increase mortality risk in heart failure, underscoring the multifactorial impact of stress hormones 1 2.
- Oxidative stress amplifies the risk associated with high cortisol, indicating complex biological interactions 2.
- The new study's linkage of adrenal gland volume (a physiological marker) to chronic stress and health outcomes provides a complementary perspective to these biochemical and mechanistic insights.
Can imaging or novel biomarkers improve chronic stress assessment and clinical practice?
While prior studies relied on serum or salivary hormone measurements and questionnaires, imaging-based biomarkers offer a promising, scalable alternative for objectively assessing chronic stress. The new study is notable for operationalizing adrenal gland volume as an imaging biomarker, which could facilitate large-scale, routine assessment without added testing burden.
- Imaging-based assessment of adrenal volume may provide a non-invasive, widely accessible method to quantify chronic stress burden, as opposed to the logistical and temporal limitations of cortisol sampling [Original Study].
- Predictive utility of imaging markers must be validated against established biochemical markers; current evidence suggests that imaging-based adrenal volume correlates well with stress hormone exposure and clinical outcomes 1 2 3 4 5.
- The integration of imaging, hormonal, and psychosocial data, as done in the new study, represents a comprehensive approach to stress quantification.
- Broader clinical adoption will require further validation and assessment of whether imaging-based markers improve risk stratification and preventive care.
Future Research Questions
Although the new study provides a significant advance in the measurement of chronic stress and its health impacts, several areas remain for further investigation. Future research should explore the causal mechanisms underlying the observed associations, assess the utility of imaging biomarkers in diverse populations, and evaluate how these tools can inform clinical interventions and outcomes.
| Research Question | Relevance |
|---|---|
| Does adrenal volume measured by CT predict cardiovascular events in younger or healthier populations? | Understanding whether adrenal volume is a universal marker of chronic stress risk across age groups and health statuses is important for broad clinical application 3 4. |
| Can AI-derived adrenal volume index be used to monitor response to stress-reduction interventions? | If imaging biomarkers are sensitive to changes in stress, they could serve as objective tools to evaluate intervention efficacy, which has not been tested in current studies [Original Study, 1]. |
| What are the biological mechanisms linking adrenal enlargement, cortisol exposure, and cardiovascular disease risk? | Elucidating mechanistic pathways could inform targeted therapies and clarify the causal role of adrenal volume in disease progression 1 2 3 4. |
| How does imaging-based stress biomarker performance compare with biochemical and questionnaire-based measures in diverse clinical settings? | Direct comparison is needed to determine whether imaging biomarkers offer additive or superior predictive value, and to guide their integration into practice [Original Study, 1,2]. |
| What are the long-term changes in adrenal volume in individuals with chronic stress who undergo successful treatment? | Tracking adrenal volume over time could validate its use as a dynamic marker of stress burden and recovery, which has implications for prevention and management strategies [Original Study]. |