What is the effect of elevated cortisol levels on cardiovascular health?

How Cortisol Levels Affect the Heart

Elevated cortisol levels directly damage the cardiovascular system through multiple mechanisms, increasing cardiovascular mortality risk by 5-fold, independent of traditional risk factors. 1

Direct Cardiovascular Effects

Hypertension and Blood Pressure

• Cortisol induces dose-dependent hypertension, with oral doses of 80-200 mg/day increasing systolic blood pressure by approximately 15 mmHg within 24 hours. 2
• The hypertensive effect occurs through sodium retention and volume expansion, but is not primarily mediated by mineralocorticoid receptor activation (spironolactone does not prevent cortisol-induced hypertension). 2
• Preliminary evidence suggests suppression of the nitric oxide system may be the primary mechanism of cortisol-induced hypertension, rather than increased sympathetic tone. 2
• Chronic hypercortisolism in Cushing's disease causes persistent hypertension that may not fully resolve even after achieving biochemical remission. 3

Atherosclerosis and Coronary Artery Disease

• Elevated plasma cortisol is the second strongest discriminator for coronary artery disease after cholesterol, with significant correlations between serial morning cortisol levels and moderate-to-severe coronary atherosclerosis. 4
• In patients with type 2 diabetes, elevated fasting cortisol (>800 vs. <600 nmol/L) increases ischemic heart disease risk by 58% (OR 1.58), independent of diabetes duration, glycemic control, and other cardiovascular risk factors. 5
• Chronic hypercortisolism promotes increased intima-media thickness, atherosclerotic plaque formation, left ventricular hypertrophy, and concentric remodeling, which may persist despite achieving remission. 3

Cardiac Arrhythmias

• Elevated cortisol triggers sympathetic nervous system activation, increasing catecholamine levels and causing tachycardia in healthy individuals. 6
• The European Society of Cardiology recognizes that elevated urinary catecholamines and cortisol correlate with increased heart rate and arrhythmia risk in patients with suspected hypercortisolism. 6
• High-dose corticosteroids (≥7.5 mg prednisone equivalents) increase atrial fibrillation risk substantially (OR 6.07), with the highest risk occurring at treatment initiation and with short-term high-dose use. 3

Cardiovascular Mortality and Morbidity

Mortality Risk

• Persons in the highest tertile of 24-hour urinary cortisol have a 5-fold increased risk of cardiovascular death (HR 5.00; 95% CI 2.02-12.37) over 6 years, after adjusting for sociodemographics, health indicators, and baseline cardiovascular disease. 1
• This mortality risk is specific to cardiovascular causes, not other causes of death, suggesting cortisol is particularly damaging to the cardiovascular system. 1
• The effect is consistent in persons both with and without preexisting cardiovascular disease (p interaction = 0.78). 1
• In active/persistent Cushing's disease, standardized mortality ratios range from 4.1 to 16, with myocardial infarction and stroke being primary causes. 3

Cardiovascular Events

• Hair cortisol concentrations (measuring chronic stress over months) are significantly associated with previous myocardial infarction, atrial fibrillation, and bypass surgery in a large population study of 4,821 middle-aged adults. 7
• Chronic hypercortisolism increases risk of myocardial infarction, stroke, and other vascular events, with rates not entirely normalizing even after achieving remission. 3

Metabolic and Inflammatory Mechanisms

Metabolic Syndrome Components

• Elevated cortisol correlates with classical cardiovascular risk factors: hypertension, high cholesterol, increased BMI, and waist circumference (particularly in females). 7
• In type 2 diabetes patients, elevated cortisol associates with raised fasting glucose and total cholesterol (p < 0.001), independent of confounding factors. 5
• Cushing's disease causes type 2 diabetes in up to 30% of patients and dyslipidemia in 16-64%, with low HDL, high LDL, and high triglycerides. 3

Inflammatory Pathways

• Hair cortisol levels correlate with leukocyte counts and high-sensitivity CRP, indicating a link between chronic cortisol elevation and systemic inflammation. 7
• Depression-associated hypercortisolemia involves inflammatory responses that contribute to coronary artery disease progression. 3

Thrombotic Risk

• Venous thromboembolic event incidence in endogenous Cushing's syndrome is >10-fold higher than in patients with nonfunctioning adenomas (OR 18-fold vs. healthy population). 3
• Hypercoagulability persists for months after cortisol normalization, with 30-day post-adrenalectomy VTE risk of 3.4-4.75%. 3

Cardiac Structural and Functional Changes

Depression and Anxiety-Related Effects

• Depression-associated hypercortisolemia causes impaired platelet function, heightened catecholamines, increased heart rate, altered vagal control, and reduced heart rate variability—all negatively impacting coronary heart disease prognosis. 3
• Decreased heart rate variability from anxiety-related cortisol elevation results in pathological cardiac autonomic tone alterations (increased sympathetic stimulation or impaired vagal control), both linked to mortality. 3

Clinical Implications

Screening Recommendations

• The Endocrine Society recommends screening for autonomous cortisol secretion using 1 mg dexamethasone suppression test in patients with adrenal incidentaloma presenting with tachycardia and suspected hypercortisolism. 6
• The American College of Cardiology advises monitoring for hypertension, hyperglycemia, and metabolic syndrome in patients with suspected hypercortisolism. 6

Risk Assessment

• Screening and risk assessment for cardiovascular risk factors before and after treatment is essential in patients with documented hypercortisolism. 3
• Healthcare should emphasize evaluation of patients reporting long-term stress exposure, as chronically elevated cortisol represents a relevant and significant cardiovascular risk factor. 7

Important Caveats

• Perceived stress does not correlate with hair cortisol concentrations, indicating that subjective stress reports alone are insufficient for assessing cortisol-mediated cardiovascular risk. 7
• Cardiovascular risk improvements occur with cortisol normalization, but structural changes and mortality risk may not fully resolve despite achieving biochemical remission, particularly if remission requires multiple interventions rather than single pituitary surgery. 3