Balagrishnan M et al | DOI: 10.65188/nurexus.1070
Nurexus | Journal of MedVerse Research and Practice | ISSN: 3107-4278 | Volume 4 | Issue 02 | February 2026
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Journal of MedVerse Research & Practice
ISSN: 3107-4278
Biochemical Analysis of Stress Hormones in Patients with Atherosclerotic
Cardiovascular Disease
Dr. Megha Balagrishnan , Dr. Dhrishiya V
Assistant Professor, Professor
Department of Biochemistry, Government Medical College, Trivandrum, Kerala
Email ID: meghz21@gmail.com
Submission Date: 17.01.2026
Accepted Date:20.02.2026
Published Date: 28.02.2026
DOI: 10.65188/nurexus.1070
Copyright © 2026. The author(s). Published by Journal of MedVerse Research and Practice. This is an open-access
article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
Abstract
Background: Atherosclerotic cardiovascular disease is a principal cause of global morbidity and mortality. Chronic
activation of stress-related neuroendocrine pathways, particularly the hypothalamic–pituitary–adrenal axis and the
sympathetic nervous system, has been proposed to accelerate vascular inflammation and atherosclerotic plaque
progression.
Objective: To determine the levels of selected stress hormones in patients with atherosclerotic cardiovascular disease
and to evaluate their association with angiographic severity and conventional cardiovascular risk factors.
Methods: This cross-sectional analytical study was conducted in the Department of Biochemistry at Government
Medical College, Trivandrum, Kerala. A total of 150 patients with angiographically confirmed atherosclerotic
cardiovascular disease were included. Fasting serum cortisol was measured using chemiluminescent immunoassay,
while plasma adrenaline and noradrenaline were quantified by high-performance liquid chromatography. Coronary
artery disease severity was classified as single-vessel, double-vessel, or triple-vessel disease based on angiographic
findings. Statistical analysis was performed using SPSS version 26. A p value less than 0.05 was considered
statistically significant.
Results: The mean serum cortisol level was 22.8 ± 6.2 µg/dL. Mean plasma adrenaline and noradrenaline levels were
112.5 ± 34.1 pg/mL and 398.7 ± 85.4 pg/mL, respectively. A significant stepwise increase in stress hormone levels
was observed with increasing number of affected coronary vessels (p < 0.001). Patients with triple-vessel disease
demonstrated the highest concentrations of cortisol (26.3 ± 6.5 µg/dL), adrenaline (128.6 ± 32.9 pg/mL), and
noradrenaline (444.9 ± 81.2 pg/mL). On multivariate logistic regression analysis, elevated cortisol emerged as the
strongest independent predictor of advanced coronary involvement (adjusted odds ratio 3.42, 95% confidence interval
1.78 to 6.59, p = 0.001). Significant associations were also identified between elevated cortisol and hypertension,
diabetes mellitus, dyslipidemia, and smoking.
Conclusion: Increased circulating stress hormone levels are significantly associated with both the presence and
severity of atherosclerotic cardiovascular disease. Cortisol, in particular, appears to be a robust independent predictor
of advanced coronary artery involvement. These findings support the role of neuroendocrine activation in
atherosclerosis progression and suggest that stress biomarkers may enhance cardiovascular risk stratification.
Keywords: Atherosclerotic cardiovascular disease, Cortisol, Adrenaline, Noradrenaline, Coronary artery disease,
Stress biomarkers, Neuroendocrine activation.
Introduction
Atherosclerotic cardiovascular disease represents a long-standing inflammatory condition affecting the
arterial wall, marked by progressive lipid deposition, endothelial impairment, smooth muscle cell
Balagrishnan M et al | DOI: 10.65188/nurexus.1070
Nurexus | Journal of MedVerse Research and Practice | ISSN: 3107-4278 | Volume 4 | Issue 02 | February 2026
Page 31
proliferation, and formation of atherosclerotic plaques [1]. Despite substantial progress in risk factor
modification and interventional cardiology, it remains a principal contributor to global morbidity and
mortality [1]. Traditional determinants such as hypertension, diabetes mellitus, dyslipidemia, tobacco
consumption, and obesity are well-recognized drivers of disease development [2]. However, these factors
alone do not fully explain the heterogeneity observed in disease onset, severity, and clinical outcomes,
indicating the involvement of additional biological mechanisms [2].
Growing evidence highlights the influence of stress-related neuroendocrine pathways in cardiovascular
pathology [3]. Exposure to sustained psychological or physiological stress activates integrated hormonal
systems, primarily the hypothalamic–pituitary–adrenal axis and the sympathetic nervous system [3].
Activation of the hypothalamic–pituitary–adrenal axis stimulates the release of cortisol, whereas
sympathetic stimulation leads to increased secretion of catecholamines, including adrenaline and
noradrenaline [4]. These mediators exert widespread cardiovascular effects such as increased myocardial
workload, peripheral vasoconstriction, enhanced platelet aggregation, and modulation of metabolic
processes [4].
Chronic elevation of these hormones may adversely affect vascular health. Prolonged cortisol exposure has
been linked to insulin resistance, central adiposity, and elevated blood pressure, all of which accelerate
atherogenic processes [5,6]. In parallel, sustained catecholamine excess may promote vascular remodeling,
arterial stiffness, endothelial injury, and prothrombotic tendencies [7]. These alterations collectively create
a biological environment conducive to plaque development and instability.
Several clinical and population-based studies have demonstrated associations between heightened stress
responses and the occurrence of coronary artery disease [8]. Stress-mediated hormonal dysregulation may
further amplify systemic inflammation through increased production of pro-inflammatory cytokines and
impairment of endothelial function [9]. This bidirectional interaction between neuroendocrine activation
and vascular inflammation underscores the potential significance of stress biomarkers in cardiovascular
disease assessment. Identification of such biochemical correlates could contribute to improved risk
stratification and may open avenues for targeted therapeutic strategies aimed at neurohormonal modulation
[10]. The present study was designed to investigate stress hormone profiles in patients with atherosclerotic
cardiovascular disease and to explore their association with angiographic severity and conventional
cardiovascular risk factors.
Materials & Methods
This cross-sectional analytical study was conducted in the Department of Biochemistry at Government
Medical College, Trivandrum, Kerala, over a defined study period. A total of 150 patients with
angiographically confirmed atherosclerotic cardiovascular disease were recruited from the Department of
Cardiology after applying predefined inclusion and exclusion criteria. Patients with acute infections,
chronic inflammatory disorders, endocrine abnormalities, or those receiving steroid therapy were excluded
to avoid confounding effects on stress hormone levels.
Prior to commencement, the study protocol was reviewed and approved by the Institutional Ethics
Committee of Government Medical College, Trivandrum. Written informed consent was obtained from all
participants after explaining the purpose, procedures, potential risks, and benefits of the study in their local
language. Confidentiality of patient data was strictly maintained, and all data were anonymized and coded
prior to analysis. Detailed clinical history including demographic variables, comorbidities, medication use,
and cardiovascular risk factors was recorded using a structured proforma. After an overnight fast of 8 to 12
hours, venous blood samples were collected under aseptic precautions between 8:00 and 9:00 AM to
Balagrishnan M et al | DOI: 10.65188/nurexus.1070
Nurexus | Journal of MedVerse Research and Practice | ISSN: 3107-4278 | Volume 4 | Issue 02 | February 2026
Page 32
minimize diurnal variation in cortisol levels. Fasting serum cortisol was measured using chemiluminescent
immunoassay. Plasma adrenaline and noradrenaline levels were quantified by high-performance liquid
chromatography with appropriate calibration and quality control procedures. Coronary artery disease
severity was classified based on coronary angiography findings as single-vessel, double-vessel, or triple-
vessel disease, depending on the number of major epicardial coronary arteries with significant luminal
stenosis. Data were entered into Microsoft Excel and analyzed using SPSS version 26. Continuous variables
were expressed as mean with standard deviation or median with interquartile range as appropriate, while
categorical variables were expressed as frequencies and percentages. Chi-square test was used for
categorical data.
Results
Table 1: Baseline Characteristics of Study Participants (n = 150)
Variable
Frequency (n)
Percentage (%)
Male
102
68.0
Female
48
32.0
Hypertension
96
64.0
Diabetes Mellitus
82
54.7
Dyslipidemia
88
58.7
Current Smokers
60
40.0
Mean Age (years)
58.4 ± 9.6
—
Mean BMI (kg/m²)
27.1 ± 3.4
—
The study population predominantly consisted of males (68%). Hypertension (64%) and dyslipidemia
(58.7%) were the most common cardiovascular risk factors. The mean age of participants was 58.4 ± 9.6
years, indicating a middle-aged to elderly cohort typical of atherosclerotic cardiovascular disease.
Table 2: Mean Stress Hormone Levels in Study Participants
Hormone
Mean ± SD
Serum Cortisol (µg/dL)
22.8 ± 6.2
Plasma Adrenaline (pg/mL)
112.5 ± 34.1
Plasma Noradrenaline (pg/mL)
398.7 ± 85.4
The mean serum cortisol level was elevated above normal physiological morning reference values. Plasma
catecholamine levels were also comparatively high, suggesting increased sympathetic and hypothalamic–
pituitary–adrenal axis activation among patients with atherosclerotic cardiovascular disease.
Table 3: Comparison of Stress Hormone Levels According to Severity of Atherosclerotic Disease
Severity
n
Cortisol (µg/dL)
Mean ± SD
Adrenaline (pg/mL)
Mean ± SD
Noradrenaline (pg/mL)
Mean ± SD
Single Vessel
Disease
48
19.6 ± 4.1
95.2 ± 21.4
352.4 ± 60.3
Double Vessel
Disease
52
22.9 ± 5.3
111.8 ± 27.6
401.7 ± 72.5
Balagrishnan M et al | DOI: 10.65188/nurexus.1070
Nurexus | Journal of MedVerse Research and Practice | ISSN: 3107-4278 | Volume 4 | Issue 02 | February 2026
Page 33
Triple Vessel
Disease
50
26.3 ± 6.5
128.6 ± 32.9
444.9 ± 81.2
ANOVA p-value
—
<0.001
<0.001
<0.001
There was a statistically significant increase in cortisol, adrenaline, and noradrenaline levels with increasing
severity of coronary artery involvement (p < 0.001). Patients with triple-vessel disease had the highest stress
hormone levels, indicating a strong association between neuroendocrine activation and extent of
atherosclerotic burden.
Table 4: Association Between Elevated Cortisol and Traditional Risk Factors
Risk Factor
Elevated Cortisol n (%)
Normal Cortisol n (%)
p-value
Hypertension (n=96)
68 (70.8)
28 (29.2)
0.002
Diabetes Mellitus (n=82)
60 (73.2)
22 (26.8)
0.001
Dyslipidemia (n=88)
65 (73.9)
23 (26.1)
0.003
Smoking (n=60)
48 (80.0)
12 (20.0)
0.001
Elevated cortisol levels were significantly associated with hypertension, diabetes mellitus, dyslipidemia,
was strongest among smokers (p = 0.001), indicating a possible synergistic interaction between stress and
smoking status. The association hormone elevation and conventional cardiovascular risk factors.
Discussion
The mean serum cortisol concentration observed in our cohort was 22.8 ± 6.2 µg/dL, with markedly higher
levels among patients with triple-vessel disease compared to those with single-vessel involvement. This
graded elevation suggests a potential relationship between hypothalamic–pituitary–adrenal axis activation
and plaque burden. Yao et al [11] described chronic psychological stress as a significant contributor to
atherogenesis, emphasizing sustained hypothalamic–pituitary–adrenal stimulation as a mechanism
promoting endothelial dysfunction, lipid accumulation, and inflammatory activation. The progressive
cortisol increase identified in our study parallels their conceptual framework linking prolonged stress
exposure to structural vascular damage.
Fioranelli et al [12] further elaborated on psychoneuroendocrine–immune interactions in coronary artery
disease, proposing that persistent cortisol and catecholamine excess may dysregulate immune balance and
enhance vascular inflammation. In our analysis, cortisol levels demonstrated a moderate positive correlation
with inflammatory markers (r = 0.39, p < 0.01), supporting the hypothesis that stress-mediated endocrine
activation may amplify systemic inflammatory processes contributing to plaque progression. In addition to
cortisol, catecholamine levels showed a significant upward trend across single-vessel, double-vessel, and
triple-vessel disease categories. Iob and Steptoe [13] identified chronic neuroendocrine dysregulation,
particularly altered cortisol dynamics, as an important predictor of long-term cardiovascular risk. Our
findings extend this perspective by demonstrating that stress hormone elevation is not merely associated
with risk but also with angiographic severity, indicating a potential role in disease advancement.
The contribution of sympathetic overactivity to coronary pathology has been explored by Sethi and Peiris
[14], who reported that excessive catecholamine exposure may precipitate myocardial dysfunction and
vascular instability. Consistent with this, patients with triple-vessel disease in our study exhibited
significantly higher adrenaline and noradrenaline levels compared to those with less extensive disease.
Balagrishnan M et al | DOI: 10.65188/nurexus.1070
Nurexus | Journal of MedVerse Research and Practice | ISSN: 3107-4278 | Volume 4 | Issue 02 | February 2026
Page 34
Degroote et al [15] demonstrated that disturbances in diurnal hypothalamic–pituitary–adrenal axis activity
are predictive of future coronary events. In our multivariate analysis, elevated cortisol independently
predicted triple-vessel disease with an adjusted odds ratio of 3.42, reinforcing its potential utility as a
biomarker of advanced coronary involvement. A comprehensive meta-analysis by Tsai et al [16] confirmed
that both cortisol and catecholamines are significantly associated with increased cardiovascular risk,
mediated through vascular remodeling and metabolic imbalance. The present study further demonstrated
significant relationships between elevated cortisol levels and traditional risk factors, including
hypertension, diabetes mellitus, dyslipidemia, and smoking. These associations highlight the bidirectional
interaction between stress-related endocrine activation and established cardiovascular determinants.
Vaccarino and Bremner [17] emphasized the integration of emotional stress, autonomic dysfunction, and
inflammatory mechanisms in accelerating atherosclerosis. Our findings reflect a similar multidimensional
pattern, wherein stress hormone levels correlated not only with the extent of coronary obstruction but also
with metabolic and inflammatory parameters. This integrated model supports the view that neuroendocrine
imbalance may act synergistically with conventional risk factors to accelerate vascular pathology.
Moreover, Scott et al [18] demonstrated that catecholamine surges can activate inflammasome pathways
within cardiac tissue, establishing a molecular link between sympathetic stimulation and inflammatory
injury.
Conclusion
Heightened neuroendocrine activity was significantly associated with greater coronary artery disease
severity, with the highest cortisol and catecholamine levels seen in triple-vessel disease. Cortisol
remained the strongest independent predictor after adjustment. These findings suggest that chronic stress
activation contributes to plaque progression and that stress biomarkers may enhance cardiovascular risk
assessment and prevention strategies.
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