Stress and heart attack risk: the role of cortisol according to evidence

Updated and contextualized version of an article originally published on May 6, 2014
The article retains its original focus by presenting it through a scholarly and accessible perspective, supported by verifiable references.

Authors

• Dr. A. Colonnese – Nutrition biologist 
• Roberto Panzironi –Independent researcher 

Note editoriali

• First publication: May 6, 2014
• Last update: April 20, 2026
• Version: 2026 narrative revision  

IN BRIEF

• Population studies show associations between higher cortisol levels and an increased risk of cardiovascular events and mortality, especially in elderly individuals or those with chronic stress exposure.
• Evidence primarily comes from observational studies measuring cortisol in urine, saliva, blood, or hair; some genetic studies (Mendelian randomization) offer conflicting results.
• Plausible mechanisms include effects on blood pressure, carbohydrate metabolism, inflammation, and vascular function, but a universal direct causal relationship has not been demonstrated.
• For clinical use or individual decisions, the overall picture must be evaluated: established risk factors (hypertension, diabetes, smoking, dyslipidemia) remain a priority.

Abstract: what does science say?

Cortisol is the central hormone in the stress response. Prospective observations in elderly populations and diverse cohorts indicate that higher cortisol levels — measured by different methods — are associated with a greater incidence of cardiovascular events and increased cardiovascular mortality. However, the evidence is partly heterogeneous: while observational studies suggest an association, genetic studies (Mendelian randomization) provide mixed results regarding a clear causal relationship. Methodological limitations, variability in measurements (urine, saliva, blood, hair), confounding effects, and the difference between a risk signal and a causal factor reduce the strength of the conclusions. In summary: there is biological plausibility and epidemiological evidence of association, but translation into clinical recommendations requires further confirmation and interventional studies.

Main section: what the evidence shows and how to interpret it

Observational literature includes studies on elderly and general populations that have measured cortisol in 24-hour urine, morning blood, saliva (diurnal profile), or hair (marker of chronic exposure). A study on people aged ≥65 years showed that subjects with the highest urinary cortisol levels had a significantly increased risk of death from cardiovascular causes during 6-year follow-up; this result was interpreted as an indication that high cortisol secretion may identify people at increased risk. [1]

Another important large-scale observation highlighted how altered cortisol curve patterns throughout the day (e.g., flatter slope or elevated evening levels) are associated with increased cardiovascular mortality in occupational and population cohorts. [2]

Combined analyses and reviews have consolidated the idea that increases in morning cortisol are linked to a statistically greater cardiovascular risk, with estimates indicating modest risk increases for each standard deviation of cortisol. [3] Some studies on long-term biomarkers (hair cortisol) have found significant associations with acute events such as myocardial infarction. [4]

Concurrently, genetic analyses and Mendelian randomization studies have sought to clarify whether the observed association reflects a causal relationship: the results are complex and partly discordant. Some analyses have not supported a robust causal effect of cortisol on all forms of cardiovascular disease, suggesting that cortisol's role may be partial, mediated by metabolic factors, or conditioned by specific contexts. [5]

Plausible biological mechanisms

There are biological mechanisms that make the link between cortisol and cardiovascular damage plausible: cortisol can increase blood pressure, promote insulin resistance, alter plasma lipids, contribute to chronic inflammation, and affect endothelial function. These effects, if prolonged, can promote atherosclerosis and vascular dysfunction, increasing the risk of ischemic events. However, the presence of plausibility does not equate to causal proof: many of these pathways are shared by other risk factors that can act as confounders or mediators. [3][5]

Measurement methods and their significance

Cortisol can be measured in different ways, and each reflects different aspects of exposure: the 24-hour urine sample quantifies total secretion, the morning blood sample captures resting concentration, saliva allows tracking the diurnal rhythm, and hair offers an index of cumulative exposure in the preceding weeks/months. The variability between methods explains part of the heterogeneity of results in different studies. [1][2][4]

Practical section: What it means in practice

Available results indicate that chronically elevated cortisol levels or altered secretion profiles may be an additional cardiovascular risk indicator, but do not currently constitute a single diagnostic marker to be used in isolation to decide therapies or clinical interventions. [1][2][3]

For individuals and healthcare professionals, the priority remains the management of established risk factors: blood pressure control, diabetes management, treatment of dyslipidemias, smoking cessation, regular physical activity, and adequate nutrition. In the presence of chronic stress exposure, a multidisciplinary approach that considers psychological support, behavioral strategies for stress reduction, and clinical control of metabolic factors may be useful. [7]

Measuring cortisol may make sense in specific clinical contexts (endocrinological evaluation, suspected pathological hypercortisolism), or in research settings; in general practice, there is currently no universal recommendation for cortisol screening for cardiovascular prevention. [6]

KEY POINTS TO REMEMBER

• Association: high levels or altered patterns of cortisol are associated with an increased cardiovascular risk in many observational studies. [1][2][3]
• Not proven as a sole cause: genetic and interventional evidence does not yet support a clear and generalized causation. [5]
• Different measurements measure different aspects: urine, saliva, blood, and hair are not interchangeable and should be interpreted in context. [1][4]
• Practical actions: managing established risk factors remains a priority; interventions to reduce chronic stress are plausibly useful but must integrate with standard care. [7]

Limitations of the Evidence

Most of the evidence on this topic comes from observational studies: these can show associations but do not prove causality due to possible confounders (e.g., comorbidities, lifestyle, socioeconomic conditions) and measurement bias. [1][2]

Cortisol measurements are subject to intra-individual and laboratory variability; the choice of sample (urine, saliva, blood, hair) and timing strongly influence the biological significance of the measurement. [1][4]

Genetic studies (Mendelian randomization) attempt to overcome the confounding problem, but they depend on the strength of the genetic instruments used: for cortisol, the instruments are limited, and the results have not provided unequivocal confirmation of causality. [5]

Finally, generalizability may be limited: many cohorts consist of elderly individuals or specific geographical populations, and the results do not always transfer to younger groups or those with a different prevalence of risk factors. [1][3][8]

Editorial Conclusion

Cortisol remains a biologically plausible biomarker for cardiovascular risk: numerous observational studies indicate a consistent association with worse cardiovascular outcomes and acute events. However, the evidence is not able to definitively establish a unique causal relationship that alone justifies changes in clinical practice. The results support the need to integrate considerations of stress and psychosocial well-being into cardiovascular prevention, without neglecting proven interventions on traditional risk factors. Interventional studies and research that better define biological mechanisms and evaluate whether reducing cortisol action leads to actual benefits in cardiovascular diseases are needed.

SCIENTIFIC RESEARCH

1. Vogelzangs N, Beekman ATF, Milaneschi Y, Bandinelli S, Ferrucci L, Penninx BWJH. Urinary cortisol and six-year risk of all-cause and cardiovascular mortality. J Clin Endocrinol Metab. 2010;95(11):4959-4964. https://doi.org/10.1210/jc.2010-0192. [1]
2. Wright J, Kumari M, et al. Association of diurnal patterns in salivary cortisol with all-cause and cardiovascular mortality: findings from the Whitehall II study. J Clin Endocrinol Metab. 2011;96(5):1478-1485. https://doi.org/10.1210/jc.2010-2137. [2]
3. Study on morning plasma cortisol as a cardiovascular risk factor: prospective cohorts and Mendelian randomization. Eur J Endocrinol. 2019;181:429-438. https://doi.org/10.1530/EJE-19-0161. [3]
4. Faresjö T, Strömberg S, et al. Elevated levels of cortisol in hair precede acute myocardial infarction. Sci Rep. 2020;10:22456. https://doi.org/10.1038/s41598-020-80559-9. [4]
5. Bi-directional Mendelian randomization study on cortisol and ischaemic heart disease, stroke, type 2 diabetes and CVD risk factors. BMC Med. 2020;18: (article). https://doi.org/10.1186/s12916-020-01831-3. [5]
6. Study of serum cortisol and cardiovascular risk/mortality in patients referred to coronary angiography (LURIC-derived data). J Endocr Soc. 2021;5(5):bvab017. https://doi.org/10.1210/jendso/bvab017. [6]
7. Systematic review and meta-analysis: Association of stress hormones and the risk of cardiovascular diseases. Int J Cardiol Cardiovasc Risk Prev. 2024;23:200305. https://doi.org/10.1016/j.ijcrp.2024.200305. [7]
8. Dysregulated diurnal cortisol patterns and cardiovascular mortality: findings from KORA-F3 (psychoendocrinology study). Psychoneuroendocrinology. 2022; (article e105753). https://doi.org/10.1016/j.psyneuen.2022.105753. [8]

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