Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access
Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc
Journal website https://jocmr.elmerjournals.com

Original Article

Volume 18, Number 11, November 2026, pages 859-879

When Stress Biology Meets Coronary Atherosclerosis: Diurnal Cortisol Patterns and Coronary Artery Disease Burden in Patients With Diabetes and Chronic Depression

Figures

↓  Figure 1. Morning (AM) serum cortisol, evening (PM) serum cortisol, and AM/PM cortisol ratio by group.
Figure 1.
↓  Figure 2. Scatter plot of AM vs. PM cortisol, colored by group, with overall regression line.
Figure 2.
↓  Figure 3. Cortisol AM by multivessel CAD status. AM: morning; CAD: coronary artery disease.
Figure 3.
↓  Figure 4. Cortisol PM by multivessel CAD status. CAD: coronary artery disease; PM: evening.
Figure 4.
↓  Figure 5. Cortisol AM by obstructive CAD status. AM: morning; CAD: coronary artery disease.
Figure 5.
↓  Figure 6. Cortisol PM by obstructive CAD status. CAD: coronary artery disease; PM: evening.
Figure 6.
↓  Figure 7. Forest plot of adjusted odds ratios for multivessel CAD. CAD: coronary artery disease.
Figure 7.
↓  Figure 8. Forest plot of adjusted odds ratios for obstructive CAD. CAD: coronary artery disease.
Figure 8.
↓  Figure 9. ROC curves for cortisol parameters predicting multivessel CAD. CAD: coronary artery disease; ROC: receiver operating characteristic.
Figure 9.
↓  Figure 10. ROC curves for cortisol parameters predicting obstructive CAD. CAD: coronary artery disease; ROC: receiver operating characteristic.
Figure 10.

Tables

↓  Table 1. Overview of Study Design and Participant Group Allocation
 
Study elementDescription
Study designObservational, analytical study with a case-control component
Group I (cases)50 patients with type 2 diabetes mellitus and clinician-documented chronic depression
Group II (controls)50 healthy individuals as a comparative reference group
Total sample sizeN = 100 participants

 

↓  Table 2. Definitions and Sources of Abstracted Clinical and Demographic Variables
 
VariableDefinition and clinical criteriaData source
BMI: body mass index; ICD: International Classification of Diseases.
AgeParticipant age in years at the time of enrolmentElectronic medical records
SexBiological sex of the participant (male or female)Electronic medical records
BMIBody mass index, calculated as weight (kg)/height squared (m2)Physical charts/vital logs
Diabetes mellitusConfirmed diagnosis of type 2 diabetes mellitusClinical progress notes/ICD codes
HypertensionActive clinician diagnosis or use of antihypertensive medicationMedical history/pharmacy records
DyslipidemiaDocumented abnormal lipid profile or active lipid-lowering therapyLab databases/pharmacy records
Smoking statusDocumented active tobacco use at the time of study enrolmentSocial history progress notes
Chronic depressionVerified history of a formal clinician-documented psychiatric diagnosisPsychiatric notes/consult record

 

↓  Table 3. Baseline Demographic and Clinical Characteristics of Cases (Group I, Diabetes + Chronic Depression) and Controls (Group II)
 
VariableCases (n = 50)Control (n = 50)TestStatisticP-value
Data are presented as median (IQR) or n (%). BMI: body mass index; DM: diabetes mellitus; HTN: hypertension; IQR: interquartile range.
Age (years)62.00 (55.50–66.00)62.50 (58.25–66.00)Mann–Whitney U1,177.50.6191
BMI (kg/m2)30.00 (28.00–33.75)29.00 (27.00–31.00)Mann–Whitney U1,528.50.0541
Sex (male)33 (66.0%)32 (64.0%)Chi-square0.0001.000
DM (positive)50 (100.0%)0 (0.0%)Fisher’s exact-< 0.001
HTN (positive)34 (68.0%)1 (2.0%)Fisher’s exact-< 0.001
Dyslipidemia (positive)28 (56.0%)4 (8.0%)Fisher’s exact-< 0.001
Smoking (positive)18 (36.0%)5 (10.0%)Chi-square8.1310.0044
Chronic depression history (positive)50 (100.0%)0 (0.0%)Fisher’s exact-< 0.001

 

↓  Table 4. Comparison of Diurnal Serum Cortisol Parameters Between Cases and Controls (N = 100)
 
Cortisol parameterCases (n = 50)Control (n = 50)TestStatisticP-value
Data are presented as mean ± SD or median (IQR). AM: morning; IQR: interquartile range; PM: evening; SD: standard deviation.
Cortisol AM (µg/dL)17.00 ± 3.0015.02 ± 2.63Independent t-test3.5080.0007
Cortisol PM (µg/dL)4.72 (3.92–5.73)3.21 (2.56–4.46)Mann–Whitney U1,901.5< 0.001
AM–PM difference (µg/dL)12.20 ± 3.1511.51 ± 2.83Independent t-test1.1520.2523
AM/PM ratio3.56 (2.95–4.63)4.28 (3.64–6.03)Mann–Whitney U869.00.0087

 

↓  Table 5. Paired Comparison of AM vs. PM Serum Cortisol Within Each Study Group
 
GroupAM, mean (µg/dL)PM, mean (µg/dL)Test typeStatisticP-value
AM: morning; PM: evening.
Cases17.004.80Paired t-test27.387< 0.001
Control15.023.51Paired t-test28.711< 0.001
Overall16.014.15Paired t-test39.498< 0.001

 

↓  Table 6. Correlation of Age and BMI With Cortisol Parameters, Overall and By Study Group
 
SampleVariable XVariable YCorrelation coefficient (r)P-value
Spearman correlation coefficients. AM: morning; BMI: body mass index; PM: evening.
Overall (N = 100)AgeCortisol AM0.0410.6860
AgeCortisol PM−0.0840.4065
AgeAM–PM difference0.0890.3784
AgeAM/PM ratio0.1240.2189
BMICortisol AM−0.0060.9546
BMICortisol PM0.0930.3571
BMIAM–PM difference−0.0470.6397
BMIAM/PM ratio−0.0970.3392
Cases only (n = 50)AgeCortisol AM0.0410.7762
AgeCortisol PM−0.1630.2593
AgeAM–PM difference0.0970.5024
AgeAM/PM ratio0.2020.1605
BMICortisol AM−0.2130.1375
BMICortisol PM0.0260.8553
BMIAM–PM difference−0.2550.0745
BMIAM/PM ratio−0.1500.2976
Control only (n = 50)AgeCortisol AM0.0780.5917
AgeCortisol PM0.0110.9398
AgeAM–PM difference0.0730.6127
AgeAM/PM ratio0.0530.7163
BMICortisol AM0.1580.2725
BMICortisol PM−0.0790.5863
BMIAM–PM difference0.1980.1671
BMIAM/PM ratio0.1300.3670

 

↓  Table 7. Diurnal Serum Cortisol Parameters Stratified by Multivessel Coronary Artery Disease Status Within the Case Cohort (n = 50)
 
Cortisol parameterMultivessel CAD positive (n = 37)Multivessel CAD negative (n = 13)Test typeStatisticP-value
Data are presented as mean ± SD or median (IQR). AM: morning; CAD: coronary artery disease; IQR: interquartile range; PM: evening; SD: standard deviation.
Cortisol AM (µg/dL)16.79 ± 3.1417.61 ± 2.58Independent t-test−0.8480.40
Cortisol PM (µg/dL)4.68 ± 1.515.15 ± 0.97Independent t-test−1.0600.29
AM–PM difference (µg/dL)12.11 ± 3.3712.46 ± 2.51Independent t-test−0.3360.74
AM/PM ratio3.70 (2.90–4.93)3.35 (2.95–3.90)Mann–Whitney U282.00.36

 

↓  Table 8. Diurnal Serum Cortisol Parameters Stratified by Obstructive Coronary Artery Disease Status Within the Case Cohort (n = 50)
 
Cortisol parameterObstructive CAD positive (n = 19)Obstructive CAD negative (n = 31)Test typeStatisticP-value
Data are presented as mean ± SD or median (IQR). AM: morning; CAD: coronary artery disease; IQR: interquartile range; PM: evening; SD: standard deviation.
Cortisol AM (µg/dL)17.21 ± 2.5516.87 ± 3.28Independent t-test0.3910.6978
Cortisol PM (µg/dL)4.64 ± 1.344.90 ± 1.45Independent t-test−0.6410.5246
AM–PM difference (µg/dL)12.58 ± 2.3511.97 ± 3.57Independent t-test0.6580.5136
AM/PM ratio4.03 (2.99–4.30)3.45 (2.89–4.90)Mann–Whitney U324.00.5622

 

↓  Table 9. Univariate and Multivariate Logistic Regression for Multivessel CAD, Exploratory Model
 
Model and predictorOR/aOR95% CIP-value
Exploratory analysis: with 13 multivessel-CAD-negative cases for eight covariates, the events-per-variable ratio is < 2; estimates are imprecise and may be overfit. AM: morning; aOR: adjusted odds ratio; BMI: body mass index; CAD: coronary artery disease; CI: confidence interval; OR: odds ratio; PM: evening.
Univariate models
  Cortisol AM (µg/dL)0.9100.732–1.1310.394
  Cortisol PM (µg/dL)0.7760.484–1.2420.290
  AM–PM difference (µg/dL)0.9650.787–1.1840.732
  AM/PM ratio1.3420.786–2.2890.281
Multivariate model (adjusted)
  Cortisol AM (µg/dL)0.9810.747–1.2890.892
  Cortisol PM (µg/dL)0.6100.334–1.1130.107
  Age (years)1.0180.937–1.1070.669
  Sex (male)1.0470.163–6.7420.961
  BMI (kg/m2)1.1580.930–1.4430.190
  Hypertension (positive)2.0040.439–9.1370.369
  Dyslipidemia (positive)5.1800.843–31.8150.076
  Smoking (positive)0.7190.120–4.2890.717

 

↓  Table 10. Univariate and Multivariate Logistic Regression Analysis for Predicting Obstructive Coronary Artery Disease Presence Within the Case Cohort (n = 50), Exploratory Model
 
Model and predictorOR/aOR95% CIP-value
Exploratory analysis: with 19 obstructive CAD events for eight covariates, the events-per-variable ratio is < 3; estimates are imprecise and may be overfit. AM: morning; aOR: adjusted odds ratio; BMI: body mass index; CI: confidence interval; OR: odds ratio; PM: evening.
Univariate models
  Cortisol AM (µg/dL)1.0400.857–1.2620.6911
  Cortisol PM (µg/dL)0.8710.574–1.3210.5162
  AM–PM difference (µg/dL)1.0650.884–1.2840.5058
  AM/PM ratio1.1040.727–1.6750.6433
Multivariate model (adjusted)
  Cortisol AM (µg/dL)1.1880.920–1.5330.1872
  Cortisol PM (µg/dL)0.7400.413–1.3270.3123
  Age (years)0.9120.840–0.9910.0300
  Sex (male)0.4840.099–2.3600.3695
  BMI (kg/m2)1.2080.995–1.4660.0557
  Hypertension (positive)0.4940.105–2.3310.3728
  Dyslipidemia (positive)0.2740.055–1.3580.1128
  Smoking (positive)0.3870.070–2.1280.2749

 

↓  Table 11. Exploratory ROC/AUC Diagnostic Performance of Diurnal Serum Cortisol Parameters for Predicting Multivessel and Obstructive Coronary Artery Disease Presence (Cases Only, n = 50)
 
Coronary endpoint and predictorAUC95% CIExploratory Youden-derived thresholdSensitivity (95% CI)Specificity (95% CI)
Thresholds are exploratory and derived within this sample only. 95% CIs for sensitivity and specificity were calculated with the Wilson score method. Given the small number of events (37 vs. 13 for multivessel CAD; 19 vs. 31 for obstructive CAD), all estimates are exploratory. AM: morning; AUC: area under the receiver operating characteristic curve; CI: confidence interval (2,000 bootstrap resamples); CAD: coronary artery disease; PM: evening.
Multivessel CAD
  Cortisol AM (µg/dL)0.3900.215–0.58522.638.1% (2.8–21.3)100.0% (77.2–100.0)
  Cortisol PM (µg/dL)0.4030.237–0.5745.8927.0% (15.4–43.0)84.6% (57.8–95.7)
  AM–PM difference (µg/dL)0.4680.296–0.65613.6840.5% (26.3–56.5)69.2% (42.4–87.3)
  AM/PM ratio0.5860.427–0.7434.0348.6% (33.4–64.1)76.9% (49.7–91.8)
Obstructive CAD
  Cortisol AM (µg/dL)0.5540.390–0.72315.3289.5% (68.6–97.1)32.3% (18.6–49.9)
  Cortisol PM (µg/dL)0.4380.276–0.6092.8794.7% (75.4–99.1)12.9% (5.1–28.9)
  AM–PM difference (µg/dL)0.5570.389–0.71513.2952.6% (31.7–72.7)67.7% (50.1–81.4)
  AM/PM ratio0.5500.385–0.7043.9057.9% (36.3–76.9)64.5% (46.9–78.9)