J Clin Med Res

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 17, Number 9, October 2025, pages 518-528

Clinical Significance of the Cardio-Ankle Vascular Index as a Cardiovascular Disease Risk Factor in Japanese Elderly Patients With Obesity

Figure 1. Optimal cut-off value of CAVI to detect primary CVD events using receiver operating characteristic curve analysis. The patients were divided into two groups based on the optimal cut-off value of the CAVI (cut-off value: 9.0): high CAVI group (group H) and a low CAVI group (group L). CAVI: cardio-ankle vascular index; CVD: cardiovascular disease; AUC: area under the curve.

Figure 2. Kaplan-Meier curve analysis for the incidence of primary CVD events in all patients. During the observation period, group H had a significantly higher incidence of primary CVD events than group L (P < 0.001, log-rank test). CVD: cardiovascular disease.

Figure 3. Kaplan-Meier curve analysis in patients not using RAS inhibitor and statin. During the observation period, group H had a significantly higher incidence of primary CVD events than group L (P = 0.013, log-rank test). CVD: cardiovascular disease.

**Table 1.** Baseline Clinical Characteristics
Characteristics	Overall	Group L	Group H	P value
Continuous values are mean ± SD. CAVI: cardio-ankle vascular index; BMI: body mass index; VFA: visceral fat area; SFA: subcutaneous fat area; SBP: systolic blood pressure; DBP: diastolic blood pressure; LDL-C: low-density lipoprotein cholesterol; TG: triglyceride; HDL-C: high-density lipoprotein cholesterol; FBG: fasting blood glucose; HOMA-IR: homeostasis model assessment of insulin resistance; Pre-LpL mass: preheparin serum lipoprotein lipase mass; U-8-iso-PGF2α: urinary 8-iso-prostaglandinF2α; RAS: renin-angiotensin system; Ca: calcium; SD: standard deviation.
N (male/female)	402 (147/255)	209 (73/136)	193 (74/119)	0.478
Age (years)	72 ± 5	72 ± 5	73 ± 5	0.165
CAVI	9.0 ± 1.2	8.1 ± 0.6	10.6 ± 0.8	< 0.001
BMI (kg/m²)	27.7 ± 2.2	27.9 ± 2.2	27.4 ± 2.2	0.007
VFA (cm²)	134 ± 56	123 ± 52	146 ± 53	< 0.001
SFA (cm²)	210 ± 72	216 ± 72	203 ± 72	0.056
VFA/SFA	0.7 ± 0.4	0.7 ± 0.4	0.8 ± 0.5	0.003
Smoker, n (%)	98 (24)	44 (21)	54 (28)	0.107
Hypertension, n (%)	310 (77)	162 (78)	148 (77)	0.844
SBP (mm Hg)	136 ± 15	135 ± 15	136 ± 16	0.494
DBP (mm Hg)	86 ± 11	86 ± 11	86 ± 11	0.943
Diabetes mellitus, n (%)	138 (34)	62 (30)	76 (39)	0.041
Dyslipidemia, n (%)	309 (77)	163 (78)	146 (76)	0.579
LDL-C (mg/dL)	127 ± 40	126 ± 39	129 ± 41	0.533
TG (mg/dL)	145 ± 60	144 ± 62	147 ± 58	0.555
HDL-C (mg/dL)	49 ± 16	50 ± 17	47 ± 14	0.045
FBG (mg/dL)	111 ± 25	106 ± 22	115 ± 27	< 0.001
HOMA-IR	2.2 ± 1.4	1.7 ± 1.0	2.8 ± 1.6	< 0.001
Pre-LpL mass (ng/mL)	68 ± 16	71 ± 17	65 ± 18	< 0.001
U-8-iso-PGF2α (pg/mg Cr)	335 ± 156	302 ± 130	371 ± 174	< 0.001
Medication
RAS inhibitors, n (%)	194 (48)	116 (56)	78 (40)	0.002
Ca blocker, n (%)	186 (46)	99 (47)	87 (45)	0.646
Statin, n (%)	147 (37)	86 (41)	61 (32)	0.037
Fibrate, n (%)	57 (14)	31 (15)	26 (14)	0.697
Sulfonylurea, n (%)	64 (16)	36 (17)	28 (15)	0.458

Table 1. Baseline Clinical Characteristics

Characteristics

Overall

Group L

Group H

P value

Continuous values are mean ± SD. CAVI: cardio-ankle vascular index; BMI: body mass index; VFA: visceral fat area; SFA: subcutaneous fat area; SBP: systolic blood pressure; DBP: diastolic blood pressure; LDL-C: low-density lipoprotein cholesterol; TG: triglyceride; HDL-C: high-density lipoprotein cholesterol; FBG: fasting blood glucose; HOMA-IR: homeostasis model assessment of insulin resistance; Pre-LpL mass: preheparin serum lipoprotein lipase mass; U-8-iso-PGF2α: urinary 8-iso-prostaglandinF2α; RAS: renin-angiotensin system; Ca: calcium; SD: standard deviation.

N (male/female)

402 (147/255)

209 (73/136)

193 (74/119)

0.478

Age (years)

72 ± 5

73 ± 5

0.165

CAVI

9.0 ± 1.2

8.1 ± 0.6

10.6 ± 0.8

< 0.001

BMI (kg/m²)

27.7 ± 2.2

27.9 ± 2.2

27.4 ± 2.2

0.007

VFA (cm²)

134 ± 56

123 ± 52

146 ± 53

< 0.001

SFA (cm²)

210 ± 72

216 ± 72

203 ± 72

0.056

VFA/SFA

0.7 ± 0.4

0.8 ± 0.5

0.003

Smoker, n (%)

98 (24)

44 (21)

54 (28)

0.107

Hypertension, n (%)

310 (77)

162 (78)

148 (77)

0.844

SBP (mm Hg)

136 ± 15

135 ± 15

136 ± 16

0.494

DBP (mm Hg)

86 ± 11

0.943

Diabetes mellitus, n (%)

138 (34)

62 (30)

76 (39)

0.041

Dyslipidemia, n (%)

309 (77)

163 (78)

146 (76)

0.579

LDL-C (mg/dL)

127 ± 40

126 ± 39

129 ± 41

0.533

TG (mg/dL)

145 ± 60

144 ± 62

147 ± 58

0.555

HDL-C (mg/dL)

49 ± 16

50 ± 17

47 ± 14

0.045

FBG (mg/dL)

111 ± 25

106 ± 22

115 ± 27

< 0.001

HOMA-IR

2.2 ± 1.4

1.7 ± 1.0

2.8 ± 1.6

< 0.001

Pre-LpL mass (ng/mL)

68 ± 16

71 ± 17

65 ± 18

< 0.001

U-8-iso-PGF2α (pg/mg Cr)

335 ± 156

302 ± 130

371 ± 174

< 0.001

Medication

RAS inhibitors, n (%)

194 (48)

116 (56)

78 (40)

0.002

Ca blocker, n (%)

186 (46)

99 (47)

87 (45)

0.646

Statin, n (%)

147 (37)

86 (41)

61 (32)

0.037

Fibrate, n (%)

57 (14)

31 (15)

26 (14)

0.697

Sulfonylurea, n (%)

64 (16)

36 (17)

28 (15)

0.458

**Table 2.** Clinical Characteristics at Registration of Patients With and Without Cardiovascular Disease Events
Characteristics	CVD events (-)	CVD events (+)	P value
Continuous values are mean ± SD. CVD: cardiovascular disease; BMI: body mass index; VFA: visceral fat area; SFA: subcutaneous fat area; SBP: systolic blood pressure; DBP: diastolic blood pressure; LDL-C: low-density lipoprotein cholesterol; TG: triglyceride; HDL-C: high-density lipoprotein cholesterol; FBG: fasting blood glucose; HOMA-IR: homeostasis model assessment of insulin resistance; Pre-LpL mass: preheparin serum lipoprotein lipase mass; U-8-iso-PGF2α: urinary 8-iso-prostaglandinF2α; RAS: renin-angiotensin system; SD: standard deviation.
Male/female	107/205	40/50	0.131
Age (years)	71 ± 5	73 ± 5	0.003
BMI (kg/m²)	27.7 ± 2.2	27.8 ± 2.3	0.754
VFA (cm²)	129 ± 56	153 ± 52	< 0.001
SFA (cm²)	211 ± 72	207 ± 71	0.647
VFA/SFA	0.7 ± 0.4	0.8 ± 0.5	0.052
Smoker, n (%)	74 (24)	24 (27)	0.675
Hypertension, n (%)	239 (77)	71 (79)	0.65
SBP (mm Hg)	136 ± 15	135 ± 16	0.788
DBP (mm Hg)	86 ± 11	86 ± 12	0.999
Dyslipidemia, n (%)	233 (75)	76 (84)	0.053
Diabetes mellitus, n (%)	88 (28)	50 (56)	< 0.001
LDL-C (mg/dL)	128 ± 41	127 ± 35	0.822
TG (mg/dL)	145 ± 61	145 ± 58	0.996
HDL-C (mg/dL)	49 ± 15	50 ± 18	0.487
FBG (mg/dL)	106 ± 23	128 ± 25	< 0.001
HOMA-IR	1.9 ± 1.1	3.4 ± 1.6	< 0.001
Pre-LpL mass (ng/mL)	71 ± 17	59 ± 18	< 0.001
U-8-iso-PGF2α (pg/mg Cr)	310 ± 135	424 ± 89	< 0.001
RAS inhibitors, n (%)	165 (53)	29 (32)	< 0.001
Ca blocker, n (%)	149 (48)	37 (41)	0.266
Statin, n (%)	129 (41)	18 (20)	< 0.001
Fibrate, n (%)	48 (15)	9 (10)	0.198
Sulfonylurea, n (%)	51 (16)	13 (14)	0.665

Table 2. Clinical Characteristics at Registration of Patients With and Without Cardiovascular Disease Events

Characteristics

CVD events (-)

CVD events (+)

P value

N = 312

N = 90

Continuous values are mean ± SD. CVD: cardiovascular disease; BMI: body mass index; VFA: visceral fat area; SFA: subcutaneous fat area; SBP: systolic blood pressure; DBP: diastolic blood pressure; LDL-C: low-density lipoprotein cholesterol; TG: triglyceride; HDL-C: high-density lipoprotein cholesterol; FBG: fasting blood glucose; HOMA-IR: homeostasis model assessment of insulin resistance; Pre-LpL mass: preheparin serum lipoprotein lipase mass; U-8-iso-PGF2α: urinary 8-iso-prostaglandinF2α; RAS: renin-angiotensin system; SD: standard deviation.

Male/female

107/205

40/50

0.131

Age (years)

71 ± 5

73 ± 5

0.003

BMI (kg/m²)

27.7 ± 2.2

27.8 ± 2.3

0.754

VFA (cm²)

129 ± 56

153 ± 52

< 0.001

SFA (cm²)

211 ± 72

207 ± 71

0.647

VFA/SFA

0.7 ± 0.4

0.8 ± 0.5

0.052

Smoker, n (%)

74 (24)

24 (27)

0.675

Hypertension, n (%)

239 (77)

71 (79)

0.65

SBP (mm Hg)

136 ± 15

135 ± 16

0.788

DBP (mm Hg)

86 ± 11

86 ± 12

0.999

Dyslipidemia, n (%)

233 (75)

76 (84)

0.053

Diabetes mellitus, n (%)

88 (28)

50 (56)

< 0.001

LDL-C (mg/dL)

128 ± 41

127 ± 35

0.822

TG (mg/dL)

145 ± 61

145 ± 58

0.996

HDL-C (mg/dL)

49 ± 15

50 ± 18

0.487

FBG (mg/dL)

106 ± 23

128 ± 25

< 0.001

HOMA-IR

1.9 ± 1.1

3.4 ± 1.6

< 0.001

Pre-LpL mass (ng/mL)

71 ± 17

59 ± 18

< 0.001

U-8-iso-PGF2α (pg/mg Cr)

310 ± 135

424 ± 89

< 0.001

RAS inhibitors, n (%)

165 (53)

29 (32)

< 0.001

Ca blocker, n (%)

149 (48)

37 (41)

0.266

Statin, n (%)

129 (41)

18 (20)

< 0.001

Fibrate, n (%)

48 (15)

9 (10)

0.198

Sulfonylurea, n (%)

51 (16)

13 (14)

0.665

**Table 3.** Multivariate Cox Regression Analysis for Cardiovascular Disease Events
Variable	HR	95% CI	P value
HR: hazard ratio; CI: confidence interval; RAS: renin-angiotensin system; Pre-LpL mass: preheparin serum lipoprotein lipase mass concentration; HOMA-IR: homeostasis model assessment for insulin resistance; U-8-iso-PGF2α: urinary 8-iso-prostaglandinF2α; VFA: visceral fat area.
Use of RAS inhibitors	0.44	0.27 - 0.73	0.001
Group H	2.40	1.37 - 4.24	0.002
Pre-LpL mass (≤ 52 ng/mL)	2.28	1.46 - 3.56	0.003
HOMA-IR (≥ 2.0)	2.16	1.21 - 3.87	0.009
Age (≥ 75years)	1.72	1.12 - 2.64	0.013
Use of Statin	0.47	0.25 - 0.89	0.015
U-8-iso-PGF2α (≥ 310 pg/mg Cr)	1.83	1.11 - 3.02	0.018
Diabetes mellitus	1.32	0.85 - 2.06	0.224
VFA (≥ 130 cm²)	1.29	0.80 - 2.09	0.304

Table 3. Multivariate Cox Regression Analysis for Cardiovascular Disease Events

Variable

95% CI

P value

HR: hazard ratio; CI: confidence interval; RAS: renin-angiotensin system; Pre-LpL mass: preheparin serum lipoprotein lipase mass concentration; HOMA-IR: homeostasis model assessment for insulin resistance; U-8-iso-PGF2α: urinary 8-iso-prostaglandinF2α; VFA: visceral fat area.

Use of RAS inhibitors

0.44

0.27 - 0.73

0.001

Group H

2.40

1.37 - 4.24

0.002

Pre-LpL mass (≤ 52 ng/mL)

2.28

1.46 - 3.56

0.003

HOMA-IR (≥ 2.0)

2.16

1.21 - 3.87

0.009

Age (≥ 75years)

1.72

1.12 - 2.64

0.013

Use of Statin

0.47

0.25 - 0.89

0.015

U-8-iso-PGF2α (≥ 310 pg/mg Cr)

1.83

1.11 - 3.02

0.018

Diabetes mellitus

1.32

0.85 - 2.06

0.224

VFA (≥ 130 cm²)

1.29

0.80 - 2.09

0.304