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Heart Rate Variability and renal organ damage
in hypertensive patients
P. Melilllo1, R. Izzo2, N. De Luca2, and L. Pecchia1
1Department
of Department of Electronics, Computer Science and Systems,
University of Bologna, Italy
2Departments of Clinical Medicine, Cardiovascular and Immunological
Sciences, Federico II University Hospital, Italy
3Faculty of Engineering, University of Nottingham, United Kingdom
[email protected]
Introduction
Methods and materials
Results
Discussion
Conclusion
EMBC 2012
STUDY POPULATION:
Hypertensive patients
METHODS and MATERIALS:
Retrospective analysis on a centralized database
Linear analysis of Heart Rate Variability
P. Melilllo, C. Formisano, U. Bracale, and L. Pecchia
Introduction
Methods and materials
Results
Discussion
Conclusion
EMBC 2012
STUDY POPULATION:
Hypertensive patients
METHODS and MATERIALS:
Retrospective analysis on a centralized database
Linear analysis of Heart Rate Variability
P. Melilllo, C. Formisano, U. Bracale, and L. Pecchia
Introduction
Methods and materials
Results
Discussion
Conclusion
EMBC 2012
Hypertensive subjects referred to the Hypertension Clinic of the University of Naples
Federico II from 2000 to 2010
Cardiac and carotid ultrasonography evaluation
24h Holter ECG after one-month antihypertensive therapy wash-out
Exclusion criteria: diagnosis of secondary resistant and/or uncontrolled hypertension;
previous CV disease; clinical history of cancer, liver cirrhosis and/or failure;
narcotics abuse or lifestyle changes in the last 12 months
Ethical issues
• compliance with the Human Study Committee regulations of the University of
Naples "Federico II“;
• Informed consent by each subjects.
P. Melilllo, R. Izzo, N. De Luca, and L. Pecchia
Introduction
Methods and materials
Results
Discussion
Conclusion
EMBC 2012
Glomerular filtration rate (GFR) estimated by the Modification of Diet in Renal Disease
(MDRD) formula
no kidney organ damage
Normal GFR
GFR≥90 mL/min/1.73 m2
kidney organ damage
Mild GFR
60<GFR<90 mL/min/1.73 m2
Moderate GFR
GFR≤60 mL/min/1.73 m2
Specifics lifestyle behaviors assessed by a detailed questionnaire
Blood pressure measurement according to the current guidelines
Serum creatinine, fasting plasma glucose, total-cholesterol, and triglycerides measured
with the standard methods
P. Melilllo, R. Izzo, N. De Luca, and L. Pecchia
Introduction
Methods and materials
Results
Discussion
Conclusion
EMBC 2012
Automatic QRS detector
HRV analysis according to International Guidelines*
using PhysioNet's HRV Toolkit
TIME DOMAIN MEAURES
AVNN : Average of all NN intervals [ms]
SDNN : Standard Deviation of all NN intervals [ms]
SDANN : Standard Deviation of the averages of NN intervals in all 5 min segments of the entire
recording [ms]
SDNN IDX: Mean of the standard deviations of all NN intervals for all 5 min segments of the
entire recording [ms]
rMSSD: square Root of the Mean of the Sum of the Squares of Differences between adjacent NN
intervals [ms
pNN50: percentage of differences between adjacent NN intervals that are longer than 50 ms
NN INTERVALS TIME SERIES
FREQUENCY DOMAIN MEASURES
TP: total spectral power of all NN intervals up to 0.4 Hz [ms2]
ULF: spectral power of all NN intervals between 0 and 0.003 Hz [ms2]
VLF: spectral power of all NN intervals between 0.003 and 0.04 Hz ([ms2]),
LF:spectral power of all NN intervals between 0.04 and 0.15 Hz [ms2]
HF: spectral power of all NN intervals between 0.15 and 0.4 Hz [ms2]
LF/HF: ratio of low to high frequency power (LF/HF),
*Malik, M., J. T. Bigger, et al. (1996). "Heart rate variability: Standards of measurement, physiological interpretation, and
clinical use." Eur Heart J 17(3): 354-381.
SPECTRUM
6
P. Melilllo, R. Izzo, N. De Luca, and L. Pecchia
Introduction
Methods and materials
Results
Discussion
Conclusion
EMBC 2012
Overall
Age (years)
Sex (male/female, %)
Family history of hypertension (yes/no, %)
Family history of stroke (yes/no, %)
Smokers (yes/ex/no, %)
Diabetes (yes/no, %)
Diastolic BP (mmHg)
Systolic BP (mmHg)
Pulse pressure (mmHg)
Fasting blood glucose (mmHg)
Total Cholesterol (mg/dl)
Beta-blockers (yes/no, %)
Alphabeta-blockers (yes/no,%)
Alpha-blockers (yes/no, %)
Diuretics (yes/no, %)
ACE inhibitor (yes/no, %)
Dihydropyridine (yes/no, %)
GFR
Kidney Involvement (1/2 /3,%)
IMT max
Vascular Involvement (no/ thickening/plague, %)
LVMi
Left Ventricular hypertrophy (no/yes, %)
62.4±12
63.5/46.5
57/43
18/82
17.5/20.5/62
18/82
75.6±11.9
133±22.6
57.5±17.8
102.9±24
186±40.5
33.5/66.5
10/90
8/92
43/57
37/63
26/74
77.3±18.5
24/60/16
2.24±1.56
13.5/11/75.5
130.2±30.8
40.5/59.5
Normal
56±11.4
64.6/35.4
52.1/47.9
20.8/79.2
27/17/56
18.8/81.2
73.2±13.8
124±23
51.3±14
99.7±31.9
178.9±36
31.3/68.7
10.4/89.6
6.3/93.7
35.4/64.6
33.3/66.7
25/75
51.5±6.2
eGFR
Mild
63±11.6
64.2/35.8
58.3/41.7
18.3/81.7
14/23/63
16.7/83.3
77.3±11.4*
137±20**
60±16.8*
102.9±19.9
187.7±40.4
34.2/65.8
11.7/88.3
6.7/93.3
40.8/59.2
40/60
25/75
74.3±8.7
Moderate
69.7±9.2**
59.4/40.6
59.4/40.6
12.5/87.5
16/19/66
21.9/78.1
72.6±9.6
129.5±27
57±23.2
107.4±23.5
190.3±45.2
34.4/65.6
3.1/96.9
15.6/84.4
62.5/37.5*
31.3/68.7
31.3/68.7
101.9±11.8
1.8±0.76**
19/12/69
124.3±25.9
50/50
2.23±1.21
13/11/76
132.8±32.1
37.5/62.5
2.9±2.85
6/10/84
128.9±30.9
37.5/62.5
P. Melilllo, R. Izzo, N. De Luca, and L. Pecchia
Introduction
Methods and materials
Results
Discussion
Conclusion
EMBC 2012
Normal GFR
Median
Mild GFR
Percentiles
25 th
75 th
Median
Moderate GFR
Percentiles
25 th
75 th
Median
p
Percentiles
25 th
75 th
AVNN
848.9
784.9
915.9
852.4
772.6
953.3
876.0
806.3
963.4
0.36
SDNN
119.5
102.3
146.0
111.1
92.2
141.3
113.8
98.3
141.1
0.31
SDANN
108.6
90.2
137.0
99.8
78.4
129.4
105.6
86.0
132.4
0.33
SDNN IDX
51.43
43.87
58.77
47.10
40.78
61.04
45.04
36.86
58.25
0.24
RMSSD
30.06
24.50
37.74
30.53
22.41
42.08
33.67
24.67
42.06
0.50
pNN50
7.68
3.94
11.74
7.88
2.73
17.71
10.06
4.07
12.85
0.66
TOTPWR
16124
11012
23626
13784
9042
21607
15175
10303
24713
0.36
ULF
12379
8864
18679
10708
7103
18480
12001
8215
20217
0.36
VLF
1592
1195
2368
1422
961
2405
1260
813
1959
0.11
LF
711.2
485.8
1102.0
600.6
370.2
916.7
577.2
373.5
925.4
0.15
HF
471.3
298.8
724.5
493.4
201.8
801.5
549.7
28.8
1230.2
0.44
LF/HF
1.44
1.17
2.10
1.25
0.91
1.75
0.87
0.72
1.25
<0.001
P. Melilllo, R. Izzo, N. De Luca, and L. Pecchia
Introduction
Methods and materials
Results
Discussion
Conclusion
EMBC 2012
Compared groups
Normal eGFR versus
Moderate eGFR
Mild eGFR versus
Moderate eGFR
HRV measure,
factor or covariate
Intercept
LF/HF
β
p
OR
5.856
0.977
0.020
0.033
2.655
1.079
to
6.531
Systolic BP
-0.005
0.645
0.995
0.973
to
1.017
-0.104 <0.001
0.901
0.854
to
0.951
Absence of family history
of hypertension
1.153
0.031
3.168
1.109
to
9.050
Intercept
LF/HF
Systolic BP
0.322
0.993
0.021
0.885
0.023
0.040
2.699
1.021
1.149
1.001
to
to
6.341
1.042
Age
-0.051
0.034
0.950
0.906
to
0.996
Absence of family history
of hypertension
0.758
0.091
2.134
0.887
to
5.138
Age
95% CI of OR
P. Melilllo, R. Izzo, N. De Luca, and L. Pecchia
Introduction
Methods and materials
Results
Discussion
Conclusion
EMBC 2012
Significant decreased LF/HF (marker of sympatho-vagal balance) in moderate eGFR patient
group
Adjustment for factor / covariate contributing to the development of renal TOD
 Expected influence of age and hypertension
Previous study (Gargia-Gargia, 2012) failed to show significant relationship maybe because
of the lack of frequency domain analysis
Consistence with findings of two recent studies:
• lower HRV (particularly, frequency domain measures) associated with higher risk of
progression to end-stage renal disease;
• autonomic imbalance may lead to kidney damage
Garcia-Garcia A, Gomez-Marcos MA, Recio-Rodriguez JI, Patino-Alonso MC, Rodriguez-Sanchez E, Agudo-Conde C, Garcia-Ortiz L: Office and 24-hour heart rate and target organ damage in hypertensive
patients. BMC Cardiovasc Disord 2012, 12(1):19.
Chandra P, Sands RL, Gillespie BW, Levin NW, Kotanko P, Kiser M, Finkelstein F, Hinderliter A, Pop-Busui R, Rajagopalan S et al: Predictors of heart rate variability and its prognostic significance in chronic
kidney disease. Nephrol Dial Transplant 2012, 27(2):700-709.
Brotman DJ, Bash LD, Qayyum R, Crews D, Whitsel EA, Astor BC, Coresh J: Heart rate variability predicts ESRD and CKD-related hospitalization. J Am Soc Nephrol 2010, 21(9):1560-1570.
P. Melilllo, R. Izzo, N. De Luca, and L. Pecchia
Introduction
Methods and materials
Results
Discussion
Conclusion
EMBC 2012
HRV depression associated with kidney organ damage
Decreased LF/HF corroborates the role of autonomic imbalance in kidney damage
Autonomic imbalance may lead kidney damage
The mechanisms by which abnormal autonomic balance may lead to organ
damage are unclear
Further studies are need ed:
• longitudinal and prospective to investigate causal relationship
• nonlinear and/or point process time-frequency analysis to extract more information
from HRV
• other non-invasive parameters of ANS activity to provide addition information
• automatic machine learning to develop classifiers able to detect / assess progression of
kidney disease
P. Melilllo, R. Izzo, N. De Luca, and L. Pecchia
Introduction
Methods and materials
Results
Discussion
Conclusion
EMBC 2012
Brief bibliography:
Similar studies
• Chandra P, et al. Nephrol Dial Transplant 2012, 27(2):700-709.
• Brotman DJ, et al. J Am Soc Nephrol 2010, 21(9):1560-1570.
• Garcia-Garcia A, et al. BMC Cardiovasc Disord 2012, 12(1):19.
Automatic classification
• Pecchia L, et al. IEEE Trans Bio Med Eng 2011, 58(3):800-804.
Other ANS parameters
• Melillo P, Pecchia L, et al. Biomed Eng Online 2012, 11(1):40.
Nonlinear and Point HRV analysis
• Melillo P, et al. Biomed Eng Online 2011, 10(1):96.
• Kodituwakku S, et al. Med Bio Eng Comput 2012, 50(3):261-275.
For further details, please refer also to:
“Design and assessment of disease management program for cardiac patients
via enhanced telemedicine with data-mining and pattern recognition”
Ph.D. Thesis by Paolo Melillo, also under press in a book edited by
Lambert Academic Publishing ISBN: 978-3-659-22103-3
P. Melilllo, R. Izzo, N. De Luca, and L. Pecchia