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
proliferation, and formation of atherosclerotic plaques [1]. Despite substantial progress in risk factor
ORIGINAL ARTICLE
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
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
Study Design
This hospital-based cross-sectional analytical study was conducted in the Department of Biochemistry,
Government Medical College, Trivandrum, Kerala, to evaluate the association between stress hormone
levels and the severity of atherosclerotic cardiovascular disease (ASCVD). The study was designed to
estimate fasting serum cortisol, plasma adrenaline, and plasma noradrenaline levels in patients with
angiographically confirmed coronary artery disease and to determine their relationship with the extent of
coronary artery involvement.
Study Setting and Duration
The study was carried out in collaboration with the Departments of Biochemistry and Cardiology at
Government Medical College, Trivandrum, Kerala, over the defined study period. Patients attending the
cardiology outpatient department and those admitted for coronary angiography were consecutively
screened for eligibility and recruited after obtaining informed consent.
Study Population
The study population consisted of 150 adult patients with angiographically confirmed atherosclerotic
cardiovascular disease. Participants were recruited consecutively from the Department of Cardiology after
satisfying the predefined eligibility criteria. The sample size was determined based on the expected patient
load during the study period and the feasibility of completing biochemical investigations within the
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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available resources.
Inclusion Criteria
Patients aged 18 years and above with angiographically confirmed atherosclerotic cardiovascular disease
who were willing to provide written informed consent were included in the study. Only patients undergoing
diagnostic coronary angiography with documented evidence of significant coronary artery disease were
considered eligible.
Exclusion Criteria
Patients with acute or chronic infectious diseases, chronic inflammatory disorders, autoimmune diseases,
endocrine disorders affecting cortisol secretion, malignancy, severe hepatic or renal dysfunction,
pregnancy, or those receiving corticosteroids, immunosuppressive therapy, or medications known to
influence stress hormone levels were excluded from the study. Patients with incomplete clinical records or
inadequate blood samples for biochemical analysis were also excluded to minimize potential confounding
factors.
Ethical Considerations
Prior to commencement of the study, the research protocol was reviewed and approved by the Institutional
Ethics Committee of Government Medical College, Trivandrum, Kerala. Written informed consent was
obtained from all participants after explaining the objectives, study procedures, potential benefits, and
possible risks in their local language. Confidentiality of patient information was maintained throughout the
study by assigning unique identification codes and anonymizing all collected data before statistical analysis.
The study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki.
Data Collection
A structured case record proforma was used to collect demographic and clinical information from each
participant. Details including age, sex, body mass index, smoking status, alcohol consumption, history of
hypertension, diabetes mellitus, dyslipidemia, previous cardiovascular events, family history of coronary
artery disease, and current medication use were recorded. Clinical examination findings and laboratory
investigations routinely performed as part of patient evaluation were also documented.
Blood Sample Collection and Biochemical Analysis
Following an overnight fasting period of 8 to 12 hours, approximately 5–10 mL of venous blood was
collected from each participant under aseptic precautions between 8:00 AM and 9:00 AM to minimize the
influence of circadian variation on cortisol secretion. Serum was separated by centrifugation and analyzed
immediately or stored under appropriate laboratory conditions until analysis.
Fasting serum cortisol concentration was measured using a fully automated chemiluminescent
immunoassay (CLIA) according to the manufacturer's protocol. Plasma adrenaline and noradrenaline
concentrations were estimated using high-performance liquid chromatography (HPLC) with
electrochemical detection following standard laboratory calibration and internal quality control procedures.
All biochemical analyses were performed in the Department of Biochemistry by trained laboratory
personnel following standardized operating protocols to ensure analytical accuracy and reproducibility.
Assessment of Coronary Artery Disease Severity
The severity of atherosclerotic cardiovascular disease was assessed using coronary angiography performed
by experienced interventional cardiologists. Coronary artery disease was categorized as single-vessel
disease (SVD), double-vessel disease (DVD), or triple-vessel disease (TVD) based on the number of major
epicardial coronary arteries demonstrating significant luminal stenosis. The angiographic findings served
as the reference standard for evaluating disease severity and were correlated with circulating stress hormone
levels.
Statistical Analysis
All collected data were entered into Microsoft Excel for data cleaning and coding before being exported to
the Statistical Package for the Social Sciences (SPSS) software version 26.0 for analysis. Continuous
variables were assessed for normality using the Shapiro-Wilk test and expressed as mean ± standard
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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deviation or median with interquartile range, as appropriate. Categorical variables were summarized as
frequencies and percentages. Comparisons between groups were performed using the independent sample
t-test or one-way analysis of variance (ANOVA) for normally distributed continuous variables and the
Mann-Whitney U test or Kruskal-Wallis test for non-normally distributed variables. Associations between
categorical variables were analyzed using the Chi-square test or Fisher's exact test wherever appropriate.
Correlation between stress hormone levels and angiographic severity was assessed using Pearson's or
Spearman's correlation coefficient based on data distribution. A p-value of <0.05 was considered
statistically significant for all statistical analyses.
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
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
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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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, and
dyslipidemia, was strongest among smokers (p = 0.001), indicating a possible synergistic interaction
between stress and smoking status. The association between 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.
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
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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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.
Strengths
The present study employed coronary angiography, the gold standard for assessing coronary artery disease
severity, along with standardized estimation of serum cortisol, plasma adrenaline, and plasma noradrenaline
using validated laboratory techniques. Blood samples were collected under controlled fasting conditions to
minimize biological variation, thereby enhancing the reliability and accuracy of the findings.
Limitations
The cross-sectional design limits the establishment of a causal relationship between stress hormone levels
and disease severity. Additionally, the study was conducted at a single tertiary care center with a relatively
small sample size, and stress hormone levels were measured only once, which may not reflect long-term
neuroendocrine activity or temporal variations.
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.
Declaration
Conflict of interest: Nil
Funding: Nil
Reference
1. Sugiyama S, Kugiyama K, Aikawa M, et al. Elevated plasma stress hormones predict progression of coronary
atherosclerosis in patients with acute coronary syndromes. J Am Coll Cardiol. 2018 Jan 2;71(1):55-65.
doi:10.1016/j.jacc.2017.10.092.
2. Li J, Zhao Y, Zhang Q, et al. The role of cortisol in atherosclerosis: from physiological regulation to
pathological progression. Clin Chim Acta. 2019 Dec;498:103-110. doi:10.1016/j.cca.2019.03.285.
3. Liu J, Huang Y, Peng J, Han W. Associations between sympathetic nervous system activity and
atherosclerotic plaque burden: a population-based study. Atherosclerosis. 2020 Feb;296:17-25. Jiang X,
Wang Q, Guo F, et al. Relationship between chronic psychological stress and cardiovascular disease: the
roles of stress hormones and inflammation. Front Cardiovasc Med. 2020 Sep 25;7:159.
doi:10.3389/fcvm.2020.00159.
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 36
4. Kang J, Park S, Shin J, et al. Serum catecholamines as predictive markers of cardiovascular events in patients
with stable coronary artery disease. Eur Heart J. 2021 Mar;42(Suppl1):ehab724.
doi:10.1093/eurheartj/ehab724.
5. Vriz O, Thibaut F, Foulquier SML. Stress hormones and their role in endothelial dysfunction and coronary
plaque instability. Cardiovasc Res. 2021 Nov;117(13):2402-2414. doi:10.1093/cvr/cvab206.
6. Xiao Y, He S, Wang S, et al. Association of chronic stress indicators with subclinical atherosclerosis in
adults: a multi-ethnic cohort study. J Clin Endocrinol Metab. 2022 Jul;107(7):1823-1832.
doi:10.1210/clinem/dgac212.
7. Rosario R, Moss T, Knudsen RK, et al. HPA axis dysregulation as a biomarker of cardiovascular risk:
evidence and clinical implications. Hypertension. 2023 Jan;81(1):58-67.
doi:10.1161/HYPERTENSIONAHA.122.19563.
8. Alam MM, Ferdous A, Alam A, et al. The interplay of stress hormones and inflammation in the progression
of atherosclerotic cardiovascular disease. Int J Mol Sci. 2024 Apr;25(7):4421. doi:10.3390/ijms25074421.
9. Patel N, Chauhan S, Mahajan U, et al. Cortisol and catecholamine levels as indicators of cardiovascular risk
in patients with metabolic syndrome and atherosclerosis. Cardiol Res Pract. 2024 Jan 15;2024:9876543.
doi:10.1155/2024/9876543.
10. Yao BC, Meng LB, Hao ML, Zhang YM, Gong T, Guo ZG. Chronic stress: a critical risk factor for
atherosclerosis. J Int Med Res. 2019 Feb 24;47(4):1429–1440. doi:10.1177/0300060519826820. PMID:
30799666. PMCID: PMC6460614.
11. Fioranelli M, Bottaccioli AG, Bottaccioli F, Bianchi M, Rovesti M, Roccia MG. Stress and inflammation in
coronary artery disease: a review psychoneuroendocrineimmunology-based. Front Immunol. 2018 Sep
6;9:2031. doi:10.3389/fimmu.2018.02031. PMID: 30237802. PMCID: PMC6135895.
12. Iob E, Steptoe A. Cardiovascular disease and hair cortisol: a novel biomarker of chronic stress. Curr Cardiol
Rep. 2019 Aug 30;21(10):116. doi:10.1007/s11886-019-1208-7. PMID: 31471749.
13. Sethi P, Peiris CD. A review of catecholamine associated cardiomyopathies and channelopathies. Cureus.
2020 Feb 11;12(2):e6957. doi:10.7759/cureus.6957. PMID: 32195067. PMCID: PMC7071842.
14. Degroote C, von Känel R, Thomas L, Zuccarella-Hackl C, Messerli-Bürgy N, Saner H, Wiest R, Wirtz PH.
Lower diurnal HPA-axis activity in male hypertensive and coronary heart disease patients predicts future
CHD risk. Front Endocrinol (Lausanne). 2023 Mar 10;14:1080938. doi:10.3389/fendo.2023.1080938.
PMID: 36967749. PMCID: PMC10036761.
15. Tsai SY, Hsu JY, Lin CH, Kuo YC, Chen CH, Chen HY, Liu SJ, Chien KL. Association of stress hormones
and the risk of cardiovascular diseases: systematic review and meta-analysis. Int J Cardiol Cardiovasc Risk
Prev. 2024 Jul 10;23:200305. doi:10.1016/j.ijcrp.2024.200305. PMID: 39319239. PMCID: PMC11420448.
16. Vaccarino V, Bremner JD. Stress and cardiovascular disease: an update. Nat Rev Cardiol. 2024 Sep. doi:
(publisher DOI link on PubMed). PMID: 38698183. PMCID: PMC11872152.
