Abstract
Objective:
To develop a method to correct the nonlinear effect of the heart rate (HR) on different heart rate variability (HRV) indices of heart rate variability.
Methods:
The study included 265 healthy participants (17–69 years old), a group of 36 type 1 diabetes mellitus patients, including 15 patients with positive diagnosis of cardiovascular autonomic neuropathy (CAN), and a group of 24 CAN positive type-2 spinocerebellar ataxia patients. HR and HRV indices were calculated for 5-min resting ECG recordings. The proposed correction method (CM) included the joint application of multiple regression analysis and Z-transformations of HR and HRV indices. To assess the effect of the CM, correlation analysis, multivariate factor analysis, and the ANOVA test were applied to both groups before and after corrections.
Results:
The CM was able to remove the effect of HR on HRV indices, and at the same time, were preserved the expected differences between HR and HRV indices between controls and patients. Sample size was not a factor.
Conclusion:
Our method may be considered a novel approach, and may represent an alternative to the use of currently developed procedures.
Significance:
Studies of HRV without an appropriately HR correction should not be considered in the future.
Acknowledgments
This project was supported, in part, by the State of Israel Kamea Dor-Bet Grant, and by the Children’s Autism Hope Project to G.L.
References
1. Cygankiewicz I, Zareba W, Heart rate variability. In: Buijs RM, Swaab DF, editors. Autonomic nervous system, handbook of clinical neurology. Amsetrdam: Elsevier, 2013:379–93.10.1016/B978-0-444-53491-0.00031-6Search in Google Scholar PubMed
2. Kamath MV, Watanabe MA, Upton AR. Heart rate variability (HRV) signal analysis. clinical applications. Boca Raton, FL: CRC Press, 2013.10.1201/b12756-2Search in Google Scholar
3. Malik M, Bigger JT, Camm J, Kleiger RE, Malliani A, Moss AJ. Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Eur Heart J 1996;17:354–81.10.1093/oxfordjournals.eurheartj.a014868Search in Google Scholar
4. Baron R. Heart rate variability. In: Deuschl G, Eisman A, editors. Recommendations for the practice of clinical neurophysiology: guidelines of the international federation of clinical physiology (EEG) Suppl 52. Amsterdam: Elsevier, 1999:283–6.Search in Google Scholar
5. Goldberger JJ, Johnson NP, Subacius H, Ng J, Greenland P. Comparison of the physiological and prognostic implications of the heart rate versus the RR interval. Heart Rhythm 2014;11:1925–33.10.1016/j.hrthm.2014.07.037Search in Google Scholar PubMed PubMed Central
6. Monfredi O, Lyashkov AE, Johnsen AB, Inada S, Schneider H, Wang R. Biophysical characterization of the underappreciated and important relationship between heart rate variability and heart rate. Hypertension 2014;64:1334–43.10.1161/HYPERTENSIONAHA.114.03782Search in Google Scholar PubMed PubMed Central
7. Nieminen T, Kähönen M, Kööbi T, Nikus K, Viik J. Heart rate variability is dependent on the level of heart rate. Am Heart J 2007;154:e13; author reply e5.10.1016/j.ahj.2007.04.050Search in Google Scholar PubMed
8. Pradhapan P, Tarvainen MP, Nieminen T, Lehtinen R, Nikus K, Lehtimaki T. Effect of heart rate correction on pre- and post-exercise heart rate variability to predict risk of mortality-an experimental study on the FINCAVAS cohort. Front Physiol 2014;5:208.10.3389/fphys.2014.00208Search in Google Scholar PubMed PubMed Central
9. Sacha J. Why should one normalize heart rate variability with respect to average heart rate. Front Physiol 2013;4:306.10.3389/fphys.2013.00306Search in Google Scholar PubMed PubMed Central
10. Sacha J. Heart rate contribution to the clinical value of heart rate variability. Kardiol Pol 2014;72:919–24.10.5603/KP.a2014.0116Search in Google Scholar PubMed
11. Sacha J. Interaction between heart rate and heart Rate variability. Ann Noninvasive Electrocardiol 2014;19:207–16.10.1111/anec.12148Search in Google Scholar PubMed PubMed Central
12. Sacha J. Interplay between heart rate and its variability: a prognostic game. Front Physiol 2014;5:347.10.3389/fphys.2014.00347Search in Google Scholar PubMed PubMed Central
13. Sacha J, Barabach S, Statkiewicz-Barabach G, Sacha K, Muller A, Piskorski J. How to select patients who will not benefit from ICD therapy by using heart rate and its variability? Int J Cardiol 2013;168:1655–8.10.1016/j.ijcard.2013.03.040Search in Google Scholar PubMed
14. Sacha J, Barabach S, Statkiewicz-Barabach G, Sacha K, Muller A, Piskorski J. How to strengthen or weaken the HRV dependence on heart rate–description of the method and its perspectives. Int J Cardiol 2013;168:1660–3.10.1016/j.ijcard.2013.03.038Search in Google Scholar PubMed
15. Sacha J, Barabach S, Statkiewicz-Barabach G, Sacha K, Muller A, Piskorski J. Gender differences in the interaction between heart rate and its variability - How to use it to improve the prognostic power of heart rate variability. Int J Cardiol 2014;171:e42–5.10.1016/j.ijcard.2013.11.116Search in Google Scholar PubMed
16. Sacha J, Pluta W. Different methods of heart rate variability analysis reveal different correlations of heart rate variability spectrum with average heart rate. J Electrocardiol 2005;38:47–53.10.1016/j.jelectrocard.2004.09.015Search in Google Scholar PubMed
17. Sacha J, Pluta W. Alterations of an average heart rate change heart rate variability due to mathematical reasons. Int J Cardiol 2008;128:444–7.10.1016/j.ijcard.2007.06.047Search in Google Scholar PubMed
18. Sacha J, Sobon J, Sacha K, Barabach S. Heart rate impact on the reproducibility of heart rate variability analysis. Int J Cardiol 2013;168:4257–9.10.1016/j.ijcard.2013.04.160Search in Google Scholar PubMed
19. Sacha J, Sobon J, Sacha K, Muller A, Schmidt G. Short-term deceleration capacity reveals higher reproducibility than spectral heart rate variability indices during self-monitoring at home. Int J Cardiol 2011;152:271–2.10.1016/j.ijcard.2011.08.008Search in Google Scholar PubMed
20. Montes-Brown J, Sanchez-Cruz G, Garcia AM, Estevez-Baez M, Velazquez-Perez L. Heart rate variability in type 2 spinocerebellar ataxia. Acta Neurol Scand 2010;122:329–35.Search in Google Scholar
21. Montes-Brown J, Machado A, Estevez M, Carricarte C, Velazquez-Perez L. Autonomic dysfunction in presymptomatic spinocerebellar ataxia type-2. Acta Neurol Scand 2012;125:24–9.10.1111/j.1600-0404.2011.01494.xSearch in Google Scholar PubMed
22. Boulton AJ, Vinik AI, Arrezzo JC, Bril V, Eva L, Feldman EL, et al. Diabetic Neuropathies. A statement by the American Diabetes Association. Diabetes Care 2005;28:956–62.10.2337/diacare.28.4.956Search in Google Scholar PubMed
23. Ewing DJ, Martyn CN, Young RJ, Clarke BF. The value of cardiovascular autonomic function tests: 10 years experience in diabetes. Diabetes Care 1985;8:491–8.10.2337/diacare.8.5.491Search in Google Scholar PubMed
24. Spallone V, Ziegler D, Roy F, Bernardi L, Frontoni S, Pop-Busui R. Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management. Diabetes Metab Res Rev 2011;27:639–53.10.1002/dmrr.1239Search in Google Scholar PubMed
25. Vinik AI, Erbas T. Diabetic autonomic neuropathy. Handb Clin Neurol 2013;117:279–94.10.1016/B978-0-444-53491-0.00022-5Search in Google Scholar PubMed
26. Vinik AI, Erbas T, Casellini CM. Diabetic cardiac autonomic neuropathy, inflammation and cardiovascular disease. J Diabetes Invest 2013;4:4–18.10.1111/jdi.12042Search in Google Scholar PubMed PubMed Central
27. Vinik AI, Ziegler D. Diabetic cardiovascular autonomic neuropathy. Circulation 2007;115:387–97.10.1161/CIRCULATIONAHA.106.634949Search in Google Scholar PubMed
28. Baevskii RM. Analysis of variability of cardiac rhythm in space medicine. Fiziol Cheloveka 2002;28:70–82.Search in Google Scholar
29. Apple S, Kuritzky A, Zahavi I, Zigelman M, Akselrod S. Evidence for instability of the autonomic nervous system in patients with migraine headache. Headache 1992;32:10–7.10.1111/j.1526-4610.1992.hed3201010.xSearch in Google Scholar PubMed
30. Abhishekh HA, Nisarga P, Kisan R, Meghana A, Chandran S, Trichur R, et al. Influence of age and gender on autonomic regulation of heart. J Clin Monit Comput 2013;27:259–64.10.1007/s10877-012-9424-3Search in Google Scholar PubMed
31. Dutra SG, Pereira AP, Tezini GC, Mazon JH, Martins-Pinge MC, Souza HC. Cardiac autonomic modulation is determined by gender and is independent of aerobic physical capacity in healthy participants. PLoS One 2013;8:e77092.10.1371/journal.pone.0077092Search in Google Scholar PubMed PubMed Central
32. Kapidžić A, Platiša MM, Bojić T, Kalauzi A. Nonlinear properties of cardiac rhythm and respiratory signal under paced breathing in young and middle-aged healthy participants. Med Eng Phys 2014;36:1577–84.10.1016/j.medengphy.2014.08.007Search in Google Scholar PubMed
33. Voss A, Schroeder R, Fischer C, Heitmann A, Peters A, Perz S. Influence of age and gender on complexity measures for short term heart rate variability analysis in healthy participants. Proc IEEE Engin Med Biol Soc 2013;2013:5574–7.Search in Google Scholar
34. Carricarte C, Montes-Brown J, Machado A, Rodríguez M, Estévez M. Multiple regression analysis applied to heart rate variability study: a methodological approach. Funct Neurol Rehabil Ergon 2012;2:97–103.Search in Google Scholar
35. Estévez M, Machado C, Leisman G, Estévez-Hernández T, Arias-Morales A, Machado A, et al. Spectral analysis of heart rate variability. Int J Disabil Hum Dev 2016;15:5–17.10.1515/ijdhd-2014-0025Search in Google Scholar
36. Montes-Brown J, Estévez M, Almaguer-Medero LE, Machado-García A, Machado C. Heart rate variability dynamics to active orthostatic tests in patients with spinocerebellar ataxia Type 2. Funct Neurol Rehabil Ergon 2012;2:105–13.Search in Google Scholar
37. Estévez Báez M, Iglesias-Alfonso J, Sánchez Quesada K, Serra Ortega A, Reyes Mur L, Molina Milián A. Análisis comparatico de indicadores de la actividad cronotrópica cardiaca durante el reposo en decúbito supino en pacientes diabéticos e individuos sanos. Revista CENIC Ciencias Biológicas 1997;28:170–2.Search in Google Scholar
38. Estévez Báez M, Iglesias-Alfonso J, Sánchez Quesada K, Serra Ortega A, Reyes Mur L, Molina Milián A. Respuesta a la bipedestación activa en pacientes diabéticos con signos de neuropatía vegetativa cardiovascular. Revista CENIC Ciencias Biológicas 1997;28:172–4.Search in Google Scholar
39. Estévez Báez M, Iglesias-Alfonso J, Villar-Olivera C, Manso Pérez R. Neuropatía vegetativa cardiaca. Saude para Todos 1996;7:31–5.Search in Google Scholar
40. Istenes I, Korei AE, Putz Z, Nemeth N, Martos T, Keresztes K. Heart rate variability is severely impaired among type 2 diabetic patients with hypertension. Diabetes Metab Res Rev 2014;30:305–12.10.1002/dmrr.2496Search in Google Scholar
41. Orlov S, Bril V, Orszag A, Perkins BA. Heart rate variability and sensorimotor polyneuropathy in type 1 diabetes. Diabetes Care 2012;35:809–16.10.2337/dc11-1652Search in Google Scholar
42. Romero-Mestre JC, Pereira-Despaigne OL, Licea-Puig ME, Faget-Cepero O, Perich-Amador P, Márquez-Guillén A. Variabilidad de la frecuencia cardíaca en reposo para detectar neuropatía autonómica cardiovascular en diabéticos tipo I. Rev Cubana End 1999;10:25–37.Search in Google Scholar
43. Turker Y, Aslantas Y, Aydin Y, Demirin H, Kutlucan A, Tibilli H. Heart rate variability and heart rate recovery in patients with type 1 diabetes mellitus. Acta Cardiol 2013;68:145–50.10.1080/AC.68.2.2967271Search in Google Scholar
44. Brinkley J, Nations L, Abramson RK, Hall A, Wright HH, Gabriels R, et al. Factor analysis of the aberrant Behavior checklist in individuals with autism spectrum disorders. J Autism Dev Disord 2007;37:1949–59.10.1007/s10803-006-0327-3Search in Google Scholar
45. Haring L, Mõttus R, Koch K, Trei M, Maron E. Factorial validity, measurement equivalence and cognitive performance of the cambridge neuropsychological test automated battery (CANTAB) between patients with first-episode psychosis and healthy volunteers. Psychol Med 2014; 101017/S0033291714003018.Search in Google Scholar
46. Norris M, Lecavalier L. Evaluating the use of exploratory factor analysis in developmental disability psychological research. J Autism Dev Disord 2010;40:8–20.10.1007/s10803-009-0816-2Search in Google Scholar
47. Allen JJ, Chambers AS, Towers DN. The many metrics of cardiac chronotropy: a pragmatic primer and a brief comparison of metrics. Biol Psychol 2007;74:243–62.10.1016/j.biopsycho.2006.08.005Search in Google Scholar
48. Castro N, Medina E, Gomis P, Wong S, Wagner G. Multiple factor analysis of the autonomous nervous system during PTCA. Proc. IEEE Engin Med Biol Soc 2005;1:940–3.10.1109/IEMBS.2005.1616570Search in Google Scholar
49. Fukusaki C, Kawakubo K, Yamamoto Y. Assessment of the primary effect of aging on heart rate variability in humans. Clin Auton Res 2000;10:123–30.10.1007/BF02278016Search in Google Scholar
50. Hayano J, Sakakibara Y, Yamada A, Yamada M, Mukai S, Fujinami T. Accuracy of assessment of cardiac vagal tone by heart rate variability in normal participants. Am J Cardiol 1991;67:199–204.10.1016/0002-9149(91)90445-QSearch in Google Scholar
51. Bigger JT Jr, Fleiss JL, Steinman RC, Rolnitzky LM, Kleiger RE, Rottman JN. Correlations among time and frequency domain measures of heart period variability two weeks after acute myocardial infarction. Am J Cardiol 1992;69:891–8.10.1016/0002-9149(92)90788-ZSearch in Google Scholar
52. Bigger JT Jr, Fleiss JL, Steinman RC, Rolnitzky LM, Schneider WJ, Stein PK. RR variability in healthy, middle-aged persons compared with patients with chronic coronary heart disease or recent acute myocardial infarction. Circulation 1995;91:936–43.10.1161/01.CIR.91.7.1936Search in Google Scholar
53. Bigger JT Jr, La Rovere MT, Steinman RC, Fleiss JL, Rottman JN, Rolnitzky LM. Comparison of baroreflex sensitivity and heart period variability after myocardial infarction. J Am Coll Cardiol 1989;14:1511–8.10.1016/0735-1097(89)90390-2Search in Google Scholar
54. Coumel P, Maison-Blanche P, Catuli D. Heart rate and heart rate variability in normal young adults. J Cardiovasc Electrophysiol 1994;5:899–911.10.1111/j.1540-8167.1994.tb01130.xSearch in Google Scholar
55. Stauss HM. Heart rate variability: Just a surrogate for mean heart rate? Hypertension 2014;6:1184–6.10.1161/HYPERTENSIONAHA.114.03949Search in Google Scholar
56. Billman GE. The effect of heart rate on the heart rate variability response to autonomic interventions. Front Physiol 2013;4:222.10.3389/fphys.2013.00222Search in Google Scholar
57. Melenovsky V, Simek J, Sperl M, Malik J, Wichterle D. Relation between actual heart rate and autonomic effects of beta blockade in healthy men. Am J Cardiol 2005;95:999–1002.10.1016/j.amjcard.2004.12.048Search in Google Scholar
58. Virtanen M, Kahonen M, Nieminen T, Karjalainen P, Tarvainen M, Lehtimaki T. Heart rate variability derived from exercise ECG in the detection of coronary artery disease. Physiol Meas 2007;28:1189–200.10.1088/0967-3334/28/10/005Search in Google Scholar
59. Mangin L, Swynghedauw B, Benis A, Thibault N, Lerebours G, Carre F. Relationships between heart rate and heart rate variability: study in conscious rats. J Cardiovasc Pharmacol 1998;32:601–7.10.1097/00005344-199810000-00012Search in Google Scholar
60. Zaza A, Lombardi F. Autonomic indexes based on the analysis of heart rate variability: a view from the sinus node. Cardiovasc Res 2001;50:434–42.10.1016/S0008-6363(01)00240-1Search in Google Scholar
61. Huikuri HV, Perkiomaki JS, Maestri R, Pinna GD. Clinical impact of evaluation of cardiovascular control by novel methods of heart rate dynamics. Philos Trans A Math Phys Eng Sci 2009;367:1223–38.10.1098/rsta.2008.0294Search in Google Scholar
62. Tsuji H, Larson MG, Venditti FJ Jr, Manders ES, Evans JC, Feldman CL. Impact of reduced heart rate variability on risk for cardiac events. The Framingham Heart Study. Circulation 1996;94:2850–5.10.1161/01.CIR.94.11.2850Search in Google Scholar
63. Tsuji H, Venditti FJ Jr., Manders ES, Evans JC, Larson MG, Feldman CL. Determinants of heart rate variability. J Am College Cardiol 1996;28:1539–46.10.1016/S0735-1097(96)00342-7Search in Google Scholar
64. Tsuji H, Venditti FJ Jr, Manders ES, Evans JC, Larson MG, Feldman CL. Reduced heart rate variability and mortality risk in an elderly cohort. The Framingham Heart Study. Circulation 1994;90:878–83.10.1161/01.CIR.90.2.878Search in Google Scholar
65. Binah O, Weissman A, Itskovitz-Eldor J, Michael R, Rosen MR. Integrating beat rate variability: From single cells to hearts. Heart Rhythm 2013;10:928–32.10.1016/j.hrthm.2013.02.013Search in Google Scholar
66. Papaioannou VE, Verkerk AO, Amin AS, de Bakker JM. Intracardiac origin of heart rate variability, pacemaker funny current and their possible association with critical illness. Curr Cardiol Rev 2013;9:82–96.Search in Google Scholar
67. Posokhova E, Ng D, Opel A, Masuho I, Tinker A, Biesecker LG. Essential role of the m2R-RGS6-IKACh pathway in controlling intrinsic heart rate variability. PLoS One 2013;8:e76973.10.1371/journal.pone.0076973Search in Google Scholar
68. Zaniboni M, Cacciani F, Lux RL. Beat-to-beat cycle length variability of spontaneously beating guinea pig sinoatrial cells: relative contributions of the membrane and calcium clocks. PLoS One 2014;9:e100242.10.1371/journal.pone.0100242Search in Google Scholar
69. Wydeven N, Posokhova E, Xia Z, Martemyanov KA, Wickman K. RGS6, but not RGS4, is the dominant Regulator of G protein signaling (RGS) modulator of the parasympathetic regulation of mouse heart rate. J Biol Chem 2014;289:2440–9.10.1074/jbc.M113.520742Search in Google Scholar
70. van Dijk JG, Koenderink M, Zwinderman AH, Haan J, Kramer CG, den Heijer JC. Autonomic nervous system tests depend on resting heart rate and blood pressure. J Auton Nerv Syst 1991;35:15–24.10.1016/0165-1838(91)90034-ZSearch in Google Scholar
71. Van Hoogenhuyze D, Weinstein N, Martin GJ, Weiss JS, Schaad JW, Sahyouni XN, et al. Reproducibility and relation to mean heart rate of heart rate variability in normal participants and in patients with congestive heart failure secondary to coronary artery disease. Am J Cardiol 1991;68:1668–76.10.1016/0002-9149(91)90327-HSearch in Google Scholar
72. Machado-Ferrer Y, Estevez M, Machado C, Hernandez-Cruz A, Carrick FR, Leisman G. Heart rate variability for assessing comatose patients with different Glasgow Coma Scale scores. Clin Neurophysiol 2013;124:589–97.10.1016/j.clinph.2012.09.008Search in Google Scholar PubMed
73. Machado C, Estévez M, Rodríguez R, Pérez-Nellar J, Chinchilla M, DeFina P, et al. Zolpidem arousing effect in persistent vegetative state patients: autonomic, EEG and behavioral assessment. Curr Pharm Des 2014;20:4185–202.10.2174/13816128113196660646Search in Google Scholar
74. John ER, Karmel BZ, Corning WC, Easton P, Brown D, Ahn H. Neurometrics. Science 1997;196:1393–410.10.4324/9781003162377Search in Google Scholar
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