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Heart Rate Variability and renal organ damage in hypertensive patients

Heart Rate Variability and renal organ damage in hypertensive patients . P. Melilllo 1 , R . Izzo 2 , N. De Luca 2 , and L. Pecchia 1 1 Department of Department of Electronics, Computer Science and Systems, University of Bologna, Italy

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Heart Rate Variability and renal organ damage in hypertensive patients

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  1. 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 paolo.melillo2@unibo.it

  2. Abstract EMBC 2012 The aim of this research activity is to investigate the relationship between Heart Rate Variability (HRV) and kidney organ damage STUDY POPULATION: Hypertensivepatients METHODS and MATERIALS: Retrospectiveanalysis on a centralized database Linear analysis of Heart Rate Variability P. Melilllo, C. Formisano, U. Bracale, and L. Pecchia Case study: stress due university examination [1] Student’s death in Naples during university examination Stress affects Autonomous Nervous System (ANS) Heart Rate Variability (HRV) reliable marker of ANS modulation on heart 1. Dimitriev D, Dimitriev A, Karpenko Y, Saperova E (2008) Influence of examination stress and psychoemotional characteristics on the blood pressure and heart rate regulation in female students. Human Physiology 34 (5):617-624.

  3. Da fare EMBC 2012 The aim of this research activity is to investigate the relationship between Heart Rate Variability (HRV) and kidney organ damage STUDY POPULATION: Hypertensivepatients METHODS and MATERIALS: Retrospectiveanalysis on a centralized database Linear analysis of Heart Rate Variability P. Melilllo, C. Formisano, U. Bracale, and L. Pecchia Case study: stress due university examination [1] Student’s death in Naples during university examination Stress affects Autonomous Nervous System (ANS) Heart Rate Variability (HRV) reliable marker of ANS modulation on heart 1. Dimitriev D, Dimitriev A, Karpenko Y, Saperova E (2008) Influence of examination stress and psychoemotional characteristics on the blood pressure and heart rate regulation in female students. Human Physiology 34 (5):617-624.

  4. Studypopulation EMBC 2012 Hypertensive patients registered in the Campania Salute Network • 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

  5. Clinicalprotocol EMBC 2012 Kidney organ damage assessed by Glomerular Filtration Rate Glomerular filtration rate (GFR) estimated by the Modification of Diet in Renal Disease (MDRD) formula no kidney organ damage kidney organ damage Normal GFRMild GFRModerate GFR GFR≥90 mL/min/1.73 m2 60<GFR<90 mL/min/1.73 m2 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 triglyceridesmeasured with the standard methods P. Melilllo, R. Izzo, N. De Luca, and L. Pecchia

  6. Linear HRV analysis EMBC 2012 standard long-term 24-h HRV analysis according to International Guidelines 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 intervalsbetween 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), SPECTRUM *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. P. Melilllo, R. Izzo, N. De Luca, and L. Pecchia

  7. Study sample EMBC 2012 Characteristics of the selected sample of 200 Hypertensive patients P. Melilllo, R. Izzo, N. De Luca, and L. Pecchia SDNN, TP, VLF, LF, HF, LF/HF, LFnu significantly decreased HFnu significantly increased * Wilcoxon signed rank test for paired data

  8. HRV and GFR EMBC 2012 HRV measures in the three patient groups P. Melilllo, R. Izzo, N. De Luca, and L. Pecchia SDNN, TP, VLF, LF, HF, LF/HF, LFnu significantly decreased HFnu significantly increased * Wilcoxon signed rank test for paired data

  9. Adjusted model EMBC 2012 HRV measures in the three patient groups P. Melilllo, R. Izzo, N. De Luca, and L. Pecchia SDNN, TP, VLF, LF, HF, LF/HF, LFnu significantly decreased HFnu significantly increased * Wilcoxon signed rank test for paired data

  10. Depressed HRV EMBC 2012 Autonomic imbalance and kidney damage • 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 CardiovascDisord 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. • BrotmanDJ, Bash LD, Qayyum R, Crews D, Whitsel EA, Astor BC, Coresh J: Heart rate variability predicts ESRD and CKD-related hospitalization. J Am SocNephrol 2010, 21(9):1560-1570. P. Melilllo, R. Izzo, N. De Luca, and L. Pecchia

  11. Conclusion EMBC 2012 HRV as risk factor or marker of progression of kidney organ damage? • 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

  12. Question time EMBC 2012 Thank you for your attention • Brief bibliography: • Similar studies • Chandra P, et al. Nephrol Dial Transplant 2012, 27(2):700-709. • Brotman DJ, et al. J Am SocNephrol 2010, 21(9):1560-1570. • Garcia-Garcia A, et al. BMC CardiovascDisord 2012, 12(1):19. • Automatic classification • Pecchia L, et al. IEEE Trans Bio Med Eng 2011, 58(3):800-804. • Other ANS parameters • MelilloP, 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. • KodituwakkuS, et al. Med Bio EngComput 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

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