Cardiol Res

Cardiology Research, ISSN 1923-2829 print, 1923-2837 online, Open Access

Article copyright, the authors; Journal compilation copyright, Cardiol Res and Elmer Press Inc

Journal website https://cr.elmerpub.com

Original Article

Volume 17, Number 3, June 2026, pages 156-163

Association of Circulating Brain-Derived Neurotrophic Factor With Coronary Risk Factors and Coronary Artery Disease in Patients Who Have Undergone Coronary Computed Tomography Angiography

↓ Figure 1. BDNF profile at baseline for all patients in the CAD and non-CAD groups or in each the number of VD. *P < 0.05. BDNF: brain-derived neurotrophic factor; CAD: coronary artery disease; VD: the number of significant vessel diseases.

↓ **Table 1.** Patient Characteristics at Baseline for All Patients in the CAD and Non-CAD Groups
	Non-CAD group (n = 216)	CAD group (n = 186)	Non-CAD vs. CAD group, P-value
Continuous variables are expressed as mean ± SD. Significance level was set at P < 0.05. α-GI: α-glucosidase inhibitor; ACEi/ARB: angiotensin-converting-enzyme inhibitor/angiotensin II receptor blocker; ASO: arteriosclerosis obliterans; BDNF: brain-derived neurotrophic factor; CAC: coronary artery calcification; CAD: coronary artery disease; CCB: calcium channel blocker; DU: diuretic; EF: ejection fraction; eGFR: estimated glomerular filtration rate; EPA: eicosapentaenoic acid; FBG: fasting blood glucose; Hb: hemoglobin; HbA1c: hemoglobin A1c; HDL-C: high-density lipoprotein cholesterol; hs-CRP: high-sensitivity C-reactive protein; LDL-C: low-density lipoprotein cholesterol; LVMI: left ventricular mass index; Plt: platelet; PWV: pulse wave velocity; SU: sulfonylurea; TC: total cholesterol; TG: triglyceride.
Age (years)	63 ± 14	69 ± 10	< 0.001
Gender (male) (%)	40.7	60.2	< 0.001
Body mass index (kg/m²)	23.6 ± 3.9	23.9 ± 3.9	0.419
Family history of CAD (%)	20.8	18.3	0.532
Smoking (%)	27.8	38.2	0.033
Hypertension (%)	60.7	58.6	0.685
Diabetes mellitus (%)	21.3	33.5	0.005
HbA1c (%)	5.9 ± 0.7	6.1 ± 0.8	0.005
FBG (mg/dL)	105 ± 33	113 ± 31	0.025
Dyslipidemia (%)	63.4	75	0.023
TG (mg/dL)	133 ± 123	136 ± 104	0.832
HDL-C (mg/dL)	61 ± 16	57 ± 16	0.005
LDL-C (mg/dL)	118 ± 33	114 ± 34	0.347
TC (mg/dL)	208 ± 38	202 ± 40	0.125
Hb (g/dL)	13.8 ± 1.5	14.0 ± 1.6	0.273
Plt (10³/µL)	237.2 ± 57.8	202.6 ± 52.1	0.03
hs-CRP	0.14 ± 0.43	0.14 ± 0.32	0.869
BDNF (ng/mL)	6.41 ± 3.42	5.73 ± 3.16	0.039
Chronic kidney disease (%)	26.8	26.9	1
eGFR (mL/min/1.73 m²)	70 ± 14.2	66 ± 14.8	0.002
Metabolic syndrome (%)	24.1	34.9	0.052
EF (%)	65.9 ± 7.3	63.2 ± 9.6	0.002
LVMI (g/m²)	61.2 ± 18.1	68.2 ± 22.2	< 0.001
ASO (%)	3.2	7	0.108
Lt. PWV	1510 ± 318	1698 ± 379	< 0.001
CAC score	38 ±162	458 ±773	< 0.001
Medications
ACEi/ARB (%)	28.7	38.7	0.044
CCB (%)	31.5	48.9	< 0.001
β-blocker (%)	5.6	10.8	0.065
DU (%)	5.1	8.1	0.309
Statin (%)	24.1	37.1	0.006
EPA (%)	4.2	1.6	0.154
SU (%)	2.8	8.6	0.014
α-GI (%)	1.9	2.2	1
Biguanide (%)	5.6	5.9	1

↓ Table 1. Patient Characteristics at Baseline for All Patients in the CAD and Non-CAD Groups

Non-CAD group (n = 216)

CAD group (n = 186)

Non-CAD vs. CAD group, P-value

Continuous variables are expressed as mean ± SD. Significance level was set at P < 0.05. α-GI: α-glucosidase inhibitor; ACEi/ARB: angiotensin-converting-enzyme inhibitor/angiotensin II receptor blocker; ASO: arteriosclerosis obliterans; BDNF: brain-derived neurotrophic factor; CAC: coronary artery calcification; CAD: coronary artery disease; CCB: calcium channel blocker; DU: diuretic; EF: ejection fraction; eGFR: estimated glomerular filtration rate; EPA: eicosapentaenoic acid; FBG: fasting blood glucose; Hb: hemoglobin; HbA1c: hemoglobin A1c; HDL-C: high-density lipoprotein cholesterol; hs-CRP: high-sensitivity C-reactive protein; LDL-C: low-density lipoprotein cholesterol; LVMI: left ventricular mass index; Plt: platelet; PWV: pulse wave velocity; SU: sulfonylurea; TC: total cholesterol; TG: triglyceride.

Age (years)

63 ± 14

69 ± 10

< 0.001

Gender (male) (%)

40.7

60.2

< 0.001

Body mass index (kg/m²)

23.6 ± 3.9

23.9 ± 3.9

0.419

Family history of CAD (%)

20.8

18.3

0.532

Smoking (%)

27.8

38.2

0.033

Hypertension (%)

60.7

58.6

0.685

Diabetes mellitus (%)

21.3

33.5

0.005

HbA1c (%)

5.9 ± 0.7

6.1 ± 0.8

0.005

FBG (mg/dL)

105 ± 33

113 ± 31

0.025

Dyslipidemia (%)

63.4

0.023

TG (mg/dL)

133 ± 123

136 ± 104

0.832

HDL-C (mg/dL)

61 ± 16

57 ± 16

0.005

LDL-C (mg/dL)

118 ± 33

114 ± 34

0.347

TC (mg/dL)

208 ± 38

202 ± 40

0.125

Hb (g/dL)

13.8 ± 1.5

14.0 ± 1.6

0.273

Plt (10³/µL)

237.2 ± 57.8

202.6 ± 52.1

0.03

hs-CRP

0.14 ± 0.43

0.14 ± 0.32

0.869

BDNF (ng/mL)

6.41 ± 3.42

5.73 ± 3.16

0.039

Chronic kidney disease (%)

26.8

26.9

eGFR (mL/min/1.73 m²)

70 ± 14.2

66 ± 14.8

0.002

Metabolic syndrome (%)

24.1

34.9

0.052

EF (%)

65.9 ± 7.3

63.2 ± 9.6

0.002

LVMI (g/m²)

61.2 ± 18.1

68.2 ± 22.2

< 0.001

ASO (%)

3.2

0.108

Lt. PWV

1510 ± 318

1698 ± 379

< 0.001

CAC score

38 ±162

458 ±773

< 0.001

Medications

ACEi/ARB (%)

28.7

38.7

0.044

CCB (%)

31.5

48.9

< 0.001

β-blocker (%)

5.6

10.8

0.065

DU (%)

5.1

8.1

0.309

Statin (%)

24.1

37.1

0.006

EPA (%)

4.2

1.6

0.154

SU (%)

2.8

8.6

0.014

α-GI (%)

1.9

2.2

Biguanide (%)

5.6

5.9

↓ **Table 2.** Linear Regression Analysis of BDNF With CAD and Cardiovascular Risk Factors
Variables	Estimate	95% CI	P-value
Significance level was set at P < 0.05. BDNF: brain-derived neurotrophic factor; CAC: coronary artery calcification; CAD: coronary artery disease; CI: confidence interval; hs-CRP: high-sensitivity C-reactive protein; Lt. PWV: left pulse wave velocity; Plt: platelet.
Plt	0.027	0.021–0.032	< 0.001
Hypertension	0.567	−0.043 to 1.178	0.069
Family history	0.58	−0.175 to 1.335	0.132
Smoking	0.507	−0.185 to 1.199	0.15
Chronic kidney disease	0.489	−0.193 to 1.170	0.159
Age	−0.01	−0.042 to 0.021	0.518
Male	−0.217	−0.982 to 0.549	0.578
Dyslipidemia	−0.145	−0.805 to 0.515	0.667
Lt. PWV	0	−0.001 to 0.001	0.772
Diabetes mellitus	−0.041	−0.732 to 0.650	0.908
CAC score	0	−0.001 to 0.001	0.926
CAD	0.051	−1.121 to 1.223	0.932
hs-CRP	0.277	−0.494 to 1.047	0.481

↓ Table 2. Linear Regression Analysis of BDNF With CAD and Cardiovascular Risk Factors

Variables

Estimate

95% CI

P-value

Significance level was set at P < 0.05. BDNF: brain-derived neurotrophic factor; CAC: coronary artery calcification; CAD: coronary artery disease; CI: confidence interval; hs-CRP: high-sensitivity C-reactive protein; Lt. PWV: left pulse wave velocity; Plt: platelet.

Plt

0.027

0.021–0.032

< 0.001

Hypertension

0.567

−0.043 to 1.178

0.069

Family history

0.58

−0.175 to 1.335

0.132

Smoking

0.507

−0.185 to 1.199

0.15

Chronic kidney disease

0.489

−0.193 to 1.170

0.159

Age

−0.01

−0.042 to 0.021

0.518

Male

−0.217

−0.982 to 0.549

0.578

Dyslipidemia

−0.145

−0.805 to 0.515

0.667

Lt. PWV

−0.001 to 0.001

0.772

Diabetes mellitus

−0.041

−0.732 to 0.650

0.908

CAC score

−0.001 to 0.001

0.926

CAD

0.051

−1.121 to 1.223

0.932

hs-CRP

0.277

−0.494 to 1.047

0.481

↓ **Table 3.** Multivariable Analyses of Predictors for the Presence of CAD
Variables	OR	95% CI	P-value
Significance level was set at P < 0.05. ACEi/ARB: angiotensin-converting-enzyme inhibitor/angiotensin II receptor blocker; BDNF: brain-derived neurotrophic factor; CAC: coronary artery calcification; CAD: coronary artery disease; CCB: calcium channel blocker; CI: confidence interval; EF: ejection fraction; Lt. PWV: left pulse wave velocity; OR: odds ratio; Plt: platelet; SU: sulfonylurea.
Age	1.03	1.00–1.06	0.047
Male	1.34	0.73–2.46	0.348
Smoking	1.76	0.97–3.17	0.061
Dyslipidemia	1.61	0.91–2.84	0.1
Diabetes mellitus	1.18	0.65–2.13	0.584
Lt. PWV	1	1.00–1.00	0.242
EF	0.97	0.93–1.00	0.038
CAC score	1.01	1.01–1.01	< 0.001
BDNF	0.97	0.90–1.05	0.436
Plt	1	0.99–1.01	0.938
ACEi/ARB	0.477	0.25 - 0.91	0.024
CCB	1.24	0.69–2.21	0.474
Statin	1.34	0.71–2.55	0.365
SU	1.39	0.34–5.78	0.649

↓ Table 3. Multivariable Analyses of Predictors for the Presence of CAD

Variables

95% CI

P-value

Significance level was set at P < 0.05. ACEi/ARB: angiotensin-converting-enzyme inhibitor/angiotensin II receptor blocker; BDNF: brain-derived neurotrophic factor; CAC: coronary artery calcification; CAD: coronary artery disease; CCB: calcium channel blocker; CI: confidence interval; EF: ejection fraction; Lt. PWV: left pulse wave velocity; OR: odds ratio; Plt: platelet; SU: sulfonylurea.

Age

1.03

1.00–1.06

0.047

Male

1.34

0.73–2.46

0.348

Smoking

1.76

0.97–3.17

0.061

Dyslipidemia

1.61

0.91–2.84

0.1

Diabetes mellitus

1.18

0.65–2.13

0.584

Lt. PWV

1.00–1.00

0.242

0.97

0.93–1.00

0.038

CAC score

1.01

1.01–1.01

< 0.001

BDNF

0.97

0.90–1.05

0.436

Plt

0.99–1.01

0.938

ACEi/ARB

0.477

0.25 - 0.91

0.024

CCB

1.24

0.69–2.21

0.474

Statin

1.34

0.71–2.55

0.365

1.39

0.34–5.78

0.649

↓ **Table 4.** Screening of Potential Confounders for the Association Between Plasma BDNF Levels and CAD
Added covariates	OR (95% CI)	Change-in-estimate (%)	P-value
Confounding was assessed using the change-in-estimate method. A variable was considered a confounder if its inclusion in the model changed the odds ratio of BDNF by more than 10%. Change-in-estimate (%) was computed using the exposure coefficient from logistic regression (β, i.e., log(odds ratio)) and reflects the percent change in β from the crude model after inclusion of each candidate covariate. Significance level was set at P < 0.05. BDNF: brain-derived neurotrophic factor; CAC: coronary artery calcium; CAD: coronary artery disease; CI: confidence interval; EF: ejection fraction; HbA1c: hemoglobin A1c; HDL-C: high-density lipoprotein cholesterol; Lt. PWV: left pulse wave velocity; OR: odds ratio; Plt: platelet.
Model 0 (unadjusted)	0.938 (0.883–0.997)		0.039
Model 0 + Plt	0.976 (0.909–1.05)	62.10%	0.49
Model 0 + age	0.963 (0.902–1.03)	42.30%	0.257
Model 0+ CAC score	0.955 (0.887–1.03)	30.10%	0.224
Model 0 + Lt. PWV	0.948 (0.888–1.01)	17.70%	0.099
Model 0 + HDL-C	0.933 (0.875–0.99)	6.90%	0.03
Model 0 + EF	0.935 (0.877–0.99)	3.10%	0.037
Model 0 + HbA1c	0.937 (0.879–1.00)	0.80%	0.044

↓ Table 4. Screening of Potential Confounders for the Association Between Plasma BDNF Levels and CAD

Added covariates

OR (95% CI)

Change-in-estimate (%)

P-value

Confounding was assessed using the change-in-estimate method. A variable was considered a confounder if its inclusion in the model changed the odds ratio of BDNF by more than 10%. Change-in-estimate (%) was computed using the exposure coefficient from logistic regression (β, i.e., log(odds ratio)) and reflects the percent change in β from the crude model after inclusion of each candidate covariate. Significance level was set at P < 0.05. BDNF: brain-derived neurotrophic factor; CAC: coronary artery calcium; CAD: coronary artery disease; CI: confidence interval; EF: ejection fraction; HbA1c: hemoglobin A1c; HDL-C: high-density lipoprotein cholesterol; Lt. PWV: left pulse wave velocity; OR: odds ratio; Plt: platelet.

Model 0 (unadjusted)

0.938 (0.883–0.997)

0.039

Model 0 + Plt

0.976 (0.909–1.05)

62.10%

0.49

Model 0 + age

0.963 (0.902–1.03)

42.30%

0.257

Model 0+ CAC score

0.955 (0.887–1.03)

30.10%

0.224

Model 0 + Lt. PWV

0.948 (0.888–1.01)

17.70%

0.099

Model 0 + HDL-C

0.933 (0.875–0.99)

6.90%

0.03

Model 0 + EF

0.935 (0.877–0.99)

3.10%

0.037

Model 0 + HbA1c

0.937 (0.879–1.00)

0.80%

0.044

↓ **Table 5.** Multivariable Logistic Regression Analysis of Plasma BDNF Levels for CAD With Sequential Adjustment
Model	Added covariates	OR (95% CI)	P-value
Models were constructed using sequential adjustment. Covariates were added to the model in the order listed in the table. Significance level was set at P < 0.05. BDNF: brain-derived neurotrophic factor; CAC: coronary artery calcium; CAD: coronary artery disease; CI: confidence interval; Lt. PWV: left pulse wave velocity; OR: odds ratio; Plt: platelet.
Model 0	Unadjusted	0.938 (0.883–0.997)	0.039
Model 1	Model 0 + Plt	0.976 (0.909–1.044)	0.457
Model 2	Model 1 + age	0.982 (0.915–1.054)	0.617
Model 3	Model 2 + CAC score	0.982 (0.908–1.062)	0.653
Model 4	Model 3 + Lt. PWV	0.980 (0.906–1.061)	0.624

↓ Table 5. Multivariable Logistic Regression Analysis of Plasma BDNF Levels for CAD With Sequential Adjustment

Model

Added covariates

OR (95% CI)

P-value

Models were constructed using sequential adjustment. Covariates were added to the model in the order listed in the table. Significance level was set at P < 0.05. BDNF: brain-derived neurotrophic factor; CAC: coronary artery calcium; CAD: coronary artery disease; CI: confidence interval; Lt. PWV: left pulse wave velocity; OR: odds ratio; Plt: platelet.

Model 0

Unadjusted

0.938 (0.883–0.997)

0.039

Model 1

Model 0 + Plt

0.976 (0.909–1.044)

0.457

Model 2

Model 1 + age

0.982 (0.915–1.054)

0.617

Model 3

Model 2 + CAC score

0.982 (0.908–1.062)

0.653

Model 4

Model 3 + Lt. PWV

0.980 (0.906–1.061)

0.624