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 http://www.cardiologyres.org

Original Article

Volume 11, Number 4, August 2020, pages 247-255

Skin Autofluorescence as a Predictor of First Heart Failure Hospitalization in Patients With Heart Failure With Preserved Ejection Fraction

Figure 1. Prediction of first heart failure hospitalization at follow-up period using skin autofluorescence. Receiver operating characteristics to determine the optimal cut-off point of skin AF for the first heart failure hospitalization. The area under curve was 0.770 (P < 0.001). Maximum Youden index indicated that a skin AF > 2.9 arbitrary units was optimal cut-off point to predict the first heart failure hospitalization, indicating a sensitivity of 65.1% and a specificity of 78.1%. Arrow indicates the optimal cut-off point. AF: autofluorescence; AU: arbitrary units; CI: confidence interval.

Figure 2. Kaplan-Meier curve for the incidence of first heart failure hospitalization. Patients were followed up for a median of 72.7 months (range, 6 - 100 months). During the follow-up period, 43 HF cases were hospitalized (group L, 15 cases; group H, 28 cases). The Kaplan-Meier curve demonstrated that group H exhibited a significantly higher incidence of first HF hospitalization than group L (P < 0.001, log-rank test). HF: heart failure; AF: autofluorescence; AU: arbitrary units.

**Table 1.** Characteristics of Patients
	Overall	Group L	Group H	P value
Continuous values are mean ± SD. AF: autofluorescence; IVSTd: interventricular septal thickness at end-diastole; LVDd: left ventricular end-diastolic diameter; LVEF: left ventricular ejection fraction; LAD: left atrial dimension; eGFR: estimated glomerular filtration rate; BNP: brain natriuretic peptide; hs-CRP: high-sensitivity C-reactive protein; CAVI: cardio-ankle vascular index; RAS: renin-angiotensin system.
n (male/female)	412 (105/317)	303 (79/224)	109 (26/83)	0.649
Age (years)	74 ± 8	73 ± 8	75 ± 9	0.108
Skin AF (arbitrary units)	2.7 ± 0.5	2.4 ± 0.3	3.3 ± 0.4	< 0.001
Stage B/stage C	246/166	213/90	33/76	< 0.001
Body mass index (kg/m²)	22.9 ± 3.5	22.8 ± 3.5	22.9 ± 3.6	0.821
Current smoker, n (%)	100 (24)	73 (24)	27 (25)	0.887
Ischemic heart disease, n (%)	67 (16)	51 (17)	16 (15)	0.602
Hypertension, n (%)	302 (73)	218 (72)	84 (77)	0.302
Systolic blood pressure (mm Hg)	144 ± 27	144 ± 26	144 ± 30	0.911
Diastolic blood pressure (mm Hg)	86 ± 11	86 ± 11	85 ± 10	0.251
Pulse rate (/min)	66 ± 13	65 ± 13	66 ± 12	0.419
Dyslipidemia, n (%)	227 (55)	165 (55)	62 (57)	0.663
Diabetes mellitus, n (%)	104 (25)	63 (21)	41 (38)	0.002
Hear valvular disease, n (%)	317 (77)	230 (76)	87 (80)	0.254
IVsTd (mm)	9.6 ± 1.6	9.5 ± 1.7	9.6 ± 1.4	0.726
LVDd (mm)	49.7 ± 3.6	49.6 ± 3.5	49.8 ± 3.7	0.531
LVEF (%)	68.5 ± 8.3	68.3 ± 8.3	68.9 ± 8.1	0.509
LAD (mm)	42.3 ± 5.6	42.4 ± 5.6	42.0 ± 5.6	0.448
E/e’	10.9 ± 3.5	10.6 ± 3.3	11.8 ± 3.8	0.002
Hemoglobin (g/dL)	12.7 ± 1.5	12.7 ± 1.5	12.8 ± 1.6	0.570
eGFR (mL/min/1.73 m²)	56.0 ± 22.5	58.0 ± 22.3	50.1 ± 22.1	0.001
Log-BNP (pg/mL)	2.0 ± 0.4	2.0 ± 0.4	2.1 ± 0.4	0.034
Log-hs-CRP (mg/dL)	-1.2 ± 0.5	-1.3 ± 0.5	-1.1 ± 0.4	0.001
CAVI	9.7 ± 1.2	9.4 ± 1.1	10.3 ± 1.2	< 0.001
Medication
RAS inhibitor, n (%)	268 (65)	202 (67)	66 (61)	0.252
β-blocker, n (%)	71 (17)	54 (18)	17 (16)	0.598
Diureics, n (%)	88 (21)	67 (22)	21 (19)	0.535
Statin, n (%)	116 (28)	84 (28)	32 (29)	0.746

Table 1. Characteristics of Patients

Overall

Group L

Group H

P value

Continuous values are mean ± SD. AF: autofluorescence; IVSTd: interventricular septal thickness at end-diastole; LVDd: left ventricular end-diastolic diameter; LVEF: left ventricular ejection fraction; LAD: left atrial dimension; eGFR: estimated glomerular filtration rate; BNP: brain natriuretic peptide; hs-CRP: high-sensitivity C-reactive protein; CAVI: cardio-ankle vascular index; RAS: renin-angiotensin system.

n (male/female)

412 (105/317)

303 (79/224)

109 (26/83)

0.649

Age (years)

74 ± 8

73 ± 8

75 ± 9

0.108

Skin AF (arbitrary units)

2.7 ± 0.5

2.4 ± 0.3

3.3 ± 0.4

< 0.001

Stage B/stage C

246/166

213/90

33/76

< 0.001

Body mass index (kg/m²)

22.9 ± 3.5

22.8 ± 3.5

22.9 ± 3.6

0.821

Current smoker, n (%)

100 (24)

73 (24)

27 (25)

0.887

Ischemic heart disease, n (%)

67 (16)

51 (17)

16 (15)

0.602

Hypertension, n (%)

302 (73)

218 (72)

84 (77)

0.302

Systolic blood pressure (mm Hg)

144 ± 27

144 ± 26

144 ± 30

0.911

Diastolic blood pressure (mm Hg)

86 ± 11

85 ± 10

0.251

Pulse rate (/min)

66 ± 13

65 ± 13

66 ± 12

0.419

Dyslipidemia, n (%)

227 (55)

165 (55)

62 (57)

0.663

Diabetes mellitus, n (%)

104 (25)

63 (21)

41 (38)

0.002

Hear valvular disease, n (%)

317 (77)

230 (76)

87 (80)

0.254

IVsTd (mm)

9.6 ± 1.6

9.5 ± 1.7

9.6 ± 1.4

0.726

LVDd (mm)

49.7 ± 3.6

49.6 ± 3.5

49.8 ± 3.7

0.531

LVEF (%)

68.5 ± 8.3

68.3 ± 8.3

68.9 ± 8.1

0.509

LAD (mm)

42.3 ± 5.6

42.4 ± 5.6

42.0 ± 5.6

0.448

E/e’

10.9 ± 3.5

10.6 ± 3.3

11.8 ± 3.8

0.002

Hemoglobin (g/dL)

12.7 ± 1.5

12.8 ± 1.6

0.570

eGFR (mL/min/1.73 m²)

56.0 ± 22.5

58.0 ± 22.3

50.1 ± 22.1

0.001

Log-BNP (pg/mL)

2.0 ± 0.4

2.1 ± 0.4

0.034

Log-hs-CRP (mg/dL)

-1.2 ± 0.5

-1.3 ± 0.5

-1.1 ± 0.4

0.001

CAVI

9.7 ± 1.2

9.4 ± 1.1

10.3 ± 1.2

< 0.001

Medication

RAS inhibitor, n (%)

268 (65)

202 (67)

66 (61)

0.252

β-blocker, n (%)

71 (17)

54 (18)

17 (16)

0.598

Diureics, n (%)

88 (21)

67 (22)

21 (19)

0.535

Statin, n (%)

116 (28)

84 (28)

32 (29)

0.746

**Table 2.** Clinical Parameters at Registration of Patients With and Without Heart Failure Hospitalization
	Non-HF hospitalization (n = 369)	HF hospitalization (n = 43)	P value
Continuous values are mean ± SD. HF: heart failure; IVSTd: interventricular septal thickness at end- diastole; LVDd: left ventricular end-diastolic diameter; LVEF: left ventricular ejection fraction; LAD: left atrial dimension; eGFR: estimated glomerular filtration rate; BNP: brain natriuretic peptide; hs-CRP: high-sensitivity C-reactive protein; CAVI: cardio-ankle vascular index; RAS: renin-angiotensin system.
Male/female	96/273	9/34	0.471
Age (years)	73 ± 8	79 ± 7	< 0.001
Stage B/stage C	241/128	5/38	< 0.001
Body mass index (kg/m²)	22.9 ± 3.5	22.8 ± 4.0	0.880
Current smoker, n (%)	83 (23)	17 (40)	0.013
Ischemic heart disease, n (%)	58 (16)	9 (21)	0.382
Hypertension, n (%)	267 (72)	35 (81)	0.206
Systolic blood pressure (mm Hg)	146 ± 24	146 ± 45	0.922
Diastolic blood pressure (mm Hg)	86 ± 11	83 ± 10	0.067
Pulse rate (/min)	66 ± 13	65 ± 11	0.749
Dyslipidemia, n (%)	202 (55)	25 (58)	0.673
Diabetes mellitus, n (%)	83 (23)	21 (49)	< 0.001
Hear valvular disease, n (%)	280 (76)	37 (86)	0.135
IVsTd (mm)	9.6 ± 1.7	9.4 ± 1.1	0.279
LVDd (mm)	49.6 ± 3.3	50.6 ± 4.9	0.051
LVEF (%)	68.2 ± 8.2	65.9 ± 9.1	0.092
LAD (mm)	42.3 ± 5.6	42.2 ± 5.6	0.904
E/e’	10.7 ± 3.4	13.1 ± 3.5	< 0.001
Hemoglobin (g/dL)	12.7 ± 1.5	13.1 ± 1.7	0.056
eGFR (mL/min/1.73 m²)	57.5 ± 22.3	42.9 ± 19.7	< 0.001
Log-BNP (pg/mL)	2.0 ± 0.4	2.2 ± 0.4	< 0.001
Log-hs-CRP (mg/dL)	-1.3 ± 0.5	-0.9 ± 0.5	< 0.001
CAVI	9.6 ± 1.2	10.4 ± 0.8	< 0.001
RAS inhibitor, n (%)	242 (66)	26 (60)	0.595
β-blocker, n (%)	69 (19)	2 (5)	0.021
Diureics, n (%)	81 (22)	7 (16)	0.392
Statin, n (%)	102 (28)	14 (33)	0.499

Table 2. Clinical Parameters at Registration of Patients With and Without Heart Failure Hospitalization

Non-HF hospitalization (n = 369)

HF hospitalization (n = 43)

P value

Continuous values are mean ± SD. HF: heart failure; IVSTd: interventricular septal thickness at end- diastole; LVDd: left ventricular end-diastolic diameter; LVEF: left ventricular ejection fraction; LAD: left atrial dimension; eGFR: estimated glomerular filtration rate; BNP: brain natriuretic peptide; hs-CRP: high-sensitivity C-reactive protein; CAVI: cardio-ankle vascular index; RAS: renin-angiotensin system.

Male/female

96/273

9/34

0.471

Age (years)

73 ± 8

79 ± 7

< 0.001

Stage B/stage C

241/128

5/38

< 0.001

Body mass index (kg/m²)

22.9 ± 3.5

22.8 ± 4.0

0.880

Current smoker, n (%)

83 (23)

17 (40)

0.013

Ischemic heart disease, n (%)

58 (16)

9 (21)

0.382

Hypertension, n (%)

267 (72)

35 (81)

0.206

Systolic blood pressure (mm Hg)

146 ± 24

146 ± 45

0.922

Diastolic blood pressure (mm Hg)

86 ± 11

83 ± 10

0.067

Pulse rate (/min)

66 ± 13

65 ± 11

0.749

Dyslipidemia, n (%)

202 (55)

25 (58)

0.673

Diabetes mellitus, n (%)

83 (23)

21 (49)

< 0.001

Hear valvular disease, n (%)

280 (76)

37 (86)

0.135

IVsTd (mm)

9.6 ± 1.7

9.4 ± 1.1

0.279

LVDd (mm)

49.6 ± 3.3

50.6 ± 4.9

0.051

LVEF (%)

68.2 ± 8.2

65.9 ± 9.1

0.092

LAD (mm)

42.3 ± 5.6

42.2 ± 5.6

0.904

E/e’

10.7 ± 3.4

13.1 ± 3.5

< 0.001

Hemoglobin (g/dL)

12.7 ± 1.5

13.1 ± 1.7

0.056

eGFR (mL/min/1.73 m²)

57.5 ± 22.3

42.9 ± 19.7

< 0.001

Log-BNP (pg/mL)

2.0 ± 0.4

2.2 ± 0.4

< 0.001

Log-hs-CRP (mg/dL)

-1.3 ± 0.5

-0.9 ± 0.5

< 0.001

CAVI

9.6 ± 1.2

10.4 ± 0.8

< 0.001

RAS inhibitor, n (%)

242 (66)

26 (60)

0.595

β-blocker, n (%)

69 (19)

2 (5)

0.021

Diureics, n (%)

81 (22)

7 (16)

0.392

Statin, n (%)

102 (28)

14 (33)

0.499

**Table 3.** Multivariate Cox Regression Analysis for Heart Failure Hospitalization
	HR	95% CI	P value
HR: hazard ratio; CI: confidence interval; CAVI: cardio-ankle vascular index; hs-CRP: high-sensitivity C-reactive protein; BNP: brain natriuretic peptide; eGFR: estimated glomerular filtration rate.
Analysis in all patients
Stage C	7.67	2.82 - 20.84	< 0.001
CAVI (≥ 10)	2.71	1.34 - 5.50	0.006
Group H	2.26	1.21 - 3.52	0.014
Diabetes mellitus	2.21	1.18 - 4.17	0.017
hs-CRP (≥ 0.1 mg/dL)	2.23	1.14 - 4.24	0.019
E/e’ (≥ 15)	2.10	1.01 - 4.44	0.049
BNP (≥ 200 pg/mL)	1.32	0.96 - 2.62	0.076
Age (≥ 70 years)	2.04	0.91 - 4.62	0.085
eGFR (< 60 mL/min/1.73 m²)	1.89	0.88 - 4.09	0.104
Current smoker	1.62	0.85 - 3.07	0.142
β-blocker	0.41	0.09 - 1.75	0.229
Analysis in patients with stage C
CAVI (≥ 10)	2.85	1.33 - 6.09	0.007
Group H	2.36	1.15 - 4.86	0.019
hs-CRP (≥ 0.1 mg/dL)	2.30	1.14 - 4.63	0.020
Diabetes mellitus	2.09	1.14 - 4.24	0.034
E/e’ (≥ 15)	2.11	1.01 - 4.46	0.048
BNP (≥ 200 pg/mL)	1.85	0.96 - 3.56	0.066
eGFR (< 60 mL/min/1.73 m²)	1.70	0.86 - 3.58	0.127
Age (≥ 70 years)	1.67	0.72 - 3.54	0.144
β-blocker	0.25	0.03 - 1.91	0.183
Current smoker	1.20	0.47 - 3.07	0.227

Table 3. Multivariate Cox Regression Analysis for Heart Failure Hospitalization

95% CI

P value

HR: hazard ratio; CI: confidence interval; CAVI: cardio-ankle vascular index; hs-CRP: high-sensitivity C-reactive protein; BNP: brain natriuretic peptide; eGFR: estimated glomerular filtration rate.

Analysis in all patients

Stage C

7.67

2.82 - 20.84

< 0.001

CAVI (≥ 10)

2.71

1.34 - 5.50

0.006

Group H

2.26

1.21 - 3.52

0.014

Diabetes mellitus

2.21

1.18 - 4.17

0.017

hs-CRP (≥ 0.1 mg/dL)

2.23

1.14 - 4.24

0.019

E/e’ (≥ 15)

2.10

1.01 - 4.44

0.049

BNP (≥ 200 pg/mL)

1.32

0.96 - 2.62

0.076

Age (≥ 70 years)

2.04

0.91 - 4.62

0.085

eGFR (< 60 mL/min/1.73 m²)

1.89

0.88 - 4.09

0.104

Current smoker

1.62

0.85 - 3.07

0.142

β-blocker

0.41

0.09 - 1.75

0.229

Analysis in patients with stage C

CAVI (≥ 10)

2.85

1.33 - 6.09

0.007

Group H

2.36

1.15 - 4.86

0.019

hs-CRP (≥ 0.1 mg/dL)

2.30

1.14 - 4.63

0.020

Diabetes mellitus

2.09

1.14 - 4.24

0.034

E/e’ (≥ 15)

2.11

1.01 - 4.46

0.048

BNP (≥ 200 pg/mL)

1.85

0.96 - 3.56

0.066

eGFR (< 60 mL/min/1.73 m²)

1.70

0.86 - 3.58

0.127

Age (≥ 70 years)

1.67

0.72 - 3.54

0.144

β-blocker

0.25

0.03 - 1.91

0.183

Current smoker

1.20

0.47 - 3.07

0.227