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://www.cardiologyres.org

Original Article

Volume 9, Number 4, August 2018, pages 231-238

Usefulness of the Whole Blood Passage Time as a Predictor of Primary Cardiovascular Events in Patients With Traditional Cardiovascular Risk Factors

Figure 1. Kaplan-Meier curve for the incidence of major adverse cardiovascular events. The Kaplan-Meier curve confirmed that group H had a higher incidence of major adverse cardiovascular events compared to groups M and L (log-rank test, P < 0.001).

Figure 2. Prediction of major adverse cardiovascular events at follow-up period using WBPT. A WBPT cut-off of 72.4 s yielded the largest area under the curve of 0.705 (95% confidence interval: 0.678 - 0.732), with a sensitivity of 51.7% and specificity of 85.4% for discriminating between those who did and did not experience major adverse cardiovascular events during the follow-up period. WBPT: whole blood passage time.

Figure 3. Multivariate Cox regression analysis for major adverse cardiovascular events using a combination of the WBPT and CAVI. The participants were divided into four groups according to cut-off levels of WBPT = 72.4 s and CAVI = 9, and a multivariate Cox regression analysis was performed. Having values above the cut-off for one of these factors (WBPT > 73.4 s or CAVI > 9) was associated with significantly higher HRs for major adverse cardiovascular events (HR: 3.18, 95% CI: 1.29 - 7.44, P < 0.01; HR: 3.36, 95% CI: 1.31 - 7.60, P < 0.01, respectively) than having values below these cut-offs. The HR was higher still when both factors were above the cut-off levels (HR, 10.62; 95% CI, 5.38 - 21.31; P < 0.001) compared with both factors being below the cut-offs. Adjustment factors are sex, age, diabetes mellitus, hs-CRP, and statin use. *P < 0.01 vs. patients with WBPT as ≤ 72.4 s and CAVI as ≤ 9; **P < 0.001 vs. patients with WBPT as ≤ 72.4 s and CAVI as ≤ 9. WBPT: whole blood passage time; CAVI: cardio-ankle vascular index; HR: hazard ratio, CI: confidence interval; hs-CRP: high sensitivity C reactive protein.

**Table 1.** Characteristics of Patients
	Overall	Group L	Group M	Group H	P value
Continuous values are mean ± SD. WBPT: whole blood passage time; SBP: systolic blood pressure; DBP: diastolic blood pressure; LDL: low-density lipoprotein; HDL: high-density lipoprotein; FBG: fasting blood glucose; hs-CRP: high sensitivity C reactive protein; CAVI: cardio-ankle vascular index; RAS: renin-angiotensin system. P < 0.001 vs. group L, P < 0.01 vs. group L, **P < 0.05 vs. group L, ^#P < 0.001 vs. group M, ^##P < 0.05 vs. group M.
N (male/female)	1,134 (438/696)	499 (168/331)	295 (111/184)	340 (159/181)^*##	< 0.001
Age (yrs)	67 ± 11	66 ± 11	67 ± 11	67 ± 11	0.136
WBPT (s)	57.0 ± 17.8	40.3 ± 5.2	59.6 ± 5.9	79.4 ± 8.5*^#	< 0.001
Risk factors
Obesity, n (%)	366 (32)	137 (27)	103 (35)***	126 (37)**	< 0.01
Current smoker, n (%)	227 (20)	57 (11)	56 (19) **	114 (34)^*#	< 0.001
Hypertension, n (%)	844 (74)	367 (74)	215 (73)	262 (77)	0.405
SBP(mm Hg)	140 ± 13	139 ± 11	141 ± 9	141 ± 17	0.139
DBP (mm Hg)	88 ± 16	87 ± 10	89 ± 10	89 ± 25	0.108
Dyslipidemia, n (%)	805 (71)	356 (71)	207 (70)	242 (71)	0.936
Diabetes mellitus, n (%)	282 (25)	105 (21)	71 (24)	106 (31)*^##	< 0.01
Blood findings
Hematocrit (%)	40 ± 5	39 ± 4	40 ± 5	41 ± 5*^##	< 0.001
White blood cell (/µL)	6,645 ± 1,495	6,535 ± 1,514	6,650 ± 1,463	6,801 ± 1,486	0.501
Platelet count (×10⁴/µL)	21 ± 5	21 ± 4	22 ± 5	21 ± 5	0.86
Total cholesterol (mg/dL)	223 ± 39	223 ± 40	220 ± 38	223 ± 40	0.157
LDL cholesterol (mg/dL)	146 ± 36	148 ± 37	144 ± 37	144 ± 35	0.103
Triglyceride (mg/dL)	125 ± 66	122 ± 66	122 ± 67	131 ± 64	0.098
HDL cholesterol (mg/dL)	52 ± 13	52 ± 13	51 ± 14	53 ± 13	0.546
FBG (mg/dL)	114 ± 27	111 ± 27	112 ± 26	119 ± 29*^#	< 0.001
Log-hs-CRP (mg/dL)	-1.3 ± 0.5	-1.5 ± 0.4	-1.4 ± 0.6	-1.0 ± 0.4*^#	< 0.001
CAVI	9.0 ± 1.2	8.8 ± 1.2	9.0 ± 1.2	9.4 ± 1.2^*#	< 0.001
Medication
RAS inhibitor, n (%)	418 (37)	190 (38)	115 (39)	113 (33)	0.454
Statin, n (%)	335 (30)	145 (29)	91 (31)	99 (29)	0.68
Anti-diabetic drugs, n (%)	236 (21)	97 (19)	51 (17)	88 (26)	0.174

Table 1. Characteristics of Patients

Overall

Group L

Group M

Group H

P value

Continuous values are mean ± SD. WBPT: whole blood passage time; SBP: systolic blood pressure; DBP: diastolic blood pressure; LDL: low-density lipoprotein; HDL: high-density lipoprotein; FBG: fasting blood glucose; hs-CRP: high sensitivity C reactive protein; CAVI: cardio-ankle vascular index; RAS: renin-angiotensin system. *P < 0.001 vs. group L, **P < 0.01 vs. group L, ***P < 0.05 vs. group L, ^#P < 0.001 vs. group M, ^##P < 0.05 vs. group M.

N (male/female)

1,134 (438/696)

499 (168/331)

295 (111/184)

340 (159/181)^*##

< 0.001

Age (yrs)

67 ± 11

66 ± 11

67 ± 11

0.136

WBPT (s)

57.0 ± 17.8

40.3 ± 5.2

59.6 ± 5.9

79.4 ± 8.5*^#

< 0.001

Risk factors

Obesity, n (%)

366 (32)

137 (27)

103 (35)***

126 (37)**

< 0.01

Current smoker, n (%)

227 (20)

57 (11)

56 (19) **

114 (34)^*#

< 0.001

Hypertension, n (%)

844 (74)

367 (74)

215 (73)

262 (77)

0.405

SBP(mm Hg)

140 ± 13

139 ± 11

141 ± 9

141 ± 17

0.139

DBP (mm Hg)

88 ± 16

87 ± 10

89 ± 10

89 ± 25

0.108

Dyslipidemia, n (%)

805 (71)

356 (71)

207 (70)

242 (71)

0.936

Diabetes mellitus, n (%)

282 (25)

105 (21)

71 (24)

106 (31)*^##

< 0.01

Blood findings

Hematocrit (%)

40 ± 5

39 ± 4

40 ± 5

41 ± 5*^##

< 0.001

White blood cell (/µL)

6,645 ± 1,495

6,535 ± 1,514

6,650 ± 1,463

6,801 ± 1,486

0.501

Platelet count (×10⁴/µL)

21 ± 5

21 ± 4

22 ± 5

21 ± 5

0.86

Total cholesterol (mg/dL)

223 ± 39

223 ± 40

220 ± 38

223 ± 40

0.157

LDL cholesterol (mg/dL)

146 ± 36

148 ± 37

144 ± 37

144 ± 35

0.103

Triglyceride (mg/dL)

125 ± 66

122 ± 66

122 ± 67

131 ± 64

0.098

HDL cholesterol (mg/dL)

52 ± 13

51 ± 14

53 ± 13

0.546

FBG (mg/dL)

114 ± 27

111 ± 27

112 ± 26

119 ± 29*^#

< 0.001

Log-hs-CRP (mg/dL)

-1.3 ± 0.5

-1.5 ± 0.4

-1.4 ± 0.6

-1.0 ± 0.4*^#

< 0.001

CAVI

9.0 ± 1.2

8.8 ± 1.2

9.0 ± 1.2

9.4 ± 1.2^*#

< 0.001

Medication

RAS inhibitor, n (%)

418 (37)

190 (38)

115 (39)

113 (33)

0.454

Statin, n (%)

335 (30)

145 (29)

91 (31)

99 (29)

0.68

Anti-diabetic drugs, n (%)

236 (21)

97 (19)

51 (17)

88 (26)

0.174

**Table 2.** Clinical Parameters at Registration of Patients With and Without Major Adverse Cardiovascular Event
	MACE (-)	MACE (+)	P value
Continuous values are mean ± SD. SBP: systolic blood pressure; DBP: diastolic blood pressure; LDL: low-density lipoprotein; HDL: high-density lipoprotein; FBG: fasting blood glucose; hs-CRP: high sensitivity C reactive protein; CAVI: cardio-ankle vascular index; RAS: renin-angiotensin system.
N (male/female)	1,039 (385/654)	95 (53/42)	< 0.001
Age (yrs)	66 ± 11	70 ± 9	< 0.01
Obesity, n (%)	329 (32)	37 (39)	0.146
Current smoker, n (%)	197 (19)	30 (32)	< 0.01
Hypertension, n (%)	772 (74)	72 (76)	0.751
SBP (mm Hg)	139 ± 13	146 ± 16	< 0.05
DBP (mm Hg)	88 ± 17	86 ± 11	0.286
Dyslipidemia, n (%)	738 (71)	67 (71)	0.918
Diabetes mellitus, n (%)	242 (23)	40 (42)	< 0.001
Hematocrit (%)	40 ± 5	41 ± 5	0.640
White blood cell (/µL)	6,624 ± 1,492	6,884 ± 1,484	0.102
Platelet count (×10⁴/µL)	21 ± 5	22 ± 5	0.463
Total cholesterol (mg/dL)	222 ± 39	223 ± 44	0.938
LDL cholesterol (mg/dL)	143 ± 35	147 ± 42	0.384
Triglyceride (mg/dL)	125 ± 66	125 ± 64	0.509
HDL cholesterol (mg/dL)	52 ± 13	50 ± 13	0.146
FBG (mg/dL)	113 ± 27	121 ± 27	< 0.05
Log-hs-CRP (mg/dL)	-1.3 ± 0.6	-1.1 ± 0.5	< 0.001
CAVI	9.0 ± 1.2	9.9 ± 1.1	< 0.001
RAS inhibitor, n (%)	393 (38)	25 (26)	< 0.05
Statin, n (%)	318 (31)	17 (18)	< 0.01
Anti-diabetic drug, n (%)	210 (20)	26 (27)	0.100

Table 2. Clinical Parameters at Registration of Patients With and Without Major Adverse Cardiovascular Event

MACE (-)

MACE (+)

P value

Continuous values are mean ± SD. SBP: systolic blood pressure; DBP: diastolic blood pressure; LDL: low-density lipoprotein; HDL: high-density lipoprotein; FBG: fasting blood glucose; hs-CRP: high sensitivity C reactive protein; CAVI: cardio-ankle vascular index; RAS: renin-angiotensin system.

N (male/female)

1,039 (385/654)

95 (53/42)

< 0.001

Age (yrs)

66 ± 11

70 ± 9

< 0.01

Obesity, n (%)

329 (32)

37 (39)

0.146

Current smoker, n (%)

197 (19)

30 (32)

< 0.01

Hypertension, n (%)

772 (74)

72 (76)

0.751

SBP (mm Hg)

139 ± 13

146 ± 16

< 0.05

DBP (mm Hg)

88 ± 17

86 ± 11

0.286

Dyslipidemia, n (%)

738 (71)

67 (71)

0.918

Diabetes mellitus, n (%)

242 (23)

40 (42)

< 0.001

Hematocrit (%)

40 ± 5

41 ± 5

0.640

White blood cell (/µL)

6,624 ± 1,492

6,884 ± 1,484

0.102

Platelet count (×10⁴/µL)

21 ± 5

22 ± 5

0.463

Total cholesterol (mg/dL)

222 ± 39

223 ± 44

0.938

LDL cholesterol (mg/dL)

143 ± 35

147 ± 42

0.384

Triglyceride (mg/dL)

125 ± 66

125 ± 64

0.509

HDL cholesterol (mg/dL)

52 ± 13

50 ± 13

0.146

FBG (mg/dL)

113 ± 27

121 ± 27

< 0.05

Log-hs-CRP (mg/dL)

-1.3 ± 0.6

-1.1 ± 0.5

< 0.001

CAVI

9.0 ± 1.2

9.9 ± 1.1

< 0.001

RAS inhibitor, n (%)

393 (38)

25 (26)

< 0.05

Statin, n (%)

318 (31)

17 (18)

< 0.01

Anti-diabetic drug, n (%)

210 (20)

26 (27)

0.100

**Table 3.** Multivariate Cox Regression Analysis for Major Adverse Cardiovascular Event
HR		95% CI	P value
HR: hazard ratio; CI: confidence interval; CAVI: cardio-ankle vascular index; hs-CRP: high sensitivity C reactive protein; RAS: renin-angiotensin system; SBP: systolic blood pressure.
CAVI (> 9)	2.52	1.35 - 3.53	< 0.01
Group H (vs. group L)	2.32	1.31 - 3.20	< 0.01
Sex (male)	2.05	1.30 - 3.13	< 0.01
Age (≥ 65 yrs)	1.87	1.15 - 3.07	< 0.01
Diabetes mellitus	1.69	1.11 - 2.57	< 0.05
hs-CRP (≥ 0.1mg/dL)	1.45	1.04 - 2.22	< 0.05
Statin	0.67	0.33 - 0.92	< 0.05
Current smoker	1.38	0.98 - 2.01	0.065
RAS inhibitor	0.66	0.42 - 1.04	0.073
SBP (≥ 140mm Hg)	1.23	0.80 - 1.91	0.339

Table 3. Multivariate Cox Regression Analysis for Major Adverse Cardiovascular Event

95% CI

P value

HR: hazard ratio; CI: confidence interval; CAVI: cardio-ankle vascular index; hs-CRP: high sensitivity C reactive protein; RAS: renin-angiotensin system; SBP: systolic blood pressure.

CAVI (> 9)

2.52

1.35 - 3.53

< 0.01

Group H (vs. group L)

2.32

1.31 - 3.20

< 0.01

Sex (male)

2.05

1.30 - 3.13

< 0.01

Age (≥ 65 yrs)

1.87

1.15 - 3.07

< 0.01

Diabetes mellitus

1.69

1.11 - 2.57

< 0.05

hs-CRP (≥ 0.1mg/dL)

1.45

1.04 - 2.22

< 0.05

Statin

0.67

0.33 - 0.92

< 0.05

Current smoker

1.38

0.98 - 2.01

0.065

RAS inhibitor

0.66

0.42 - 1.04

0.073

SBP (≥ 140mm Hg)

1.23

0.80 - 1.91

0.339