The study of heart rate variability in elderly patients with chronic obstructive pulmonary disease undergoing inpatient treatment in a mid-mountain environment

   Introduction. Chronic obstructive pulmonary disease (COPD) is frequently associated with cardiovascular dysfunction. Heart rate variability (HRV) analysis serves as an additional criterion for evaluating the functional status of COPD patients, reflecting the integrated state of autonomic regulation.

   Aim. To assess HRV parameters in elderly COPD patients undergoing inpatient treatment under middle-mountain climatotherapy conditions before and after a standardized therapeutic course.

   Materials and methods. Thirty-three patients (median age 67.5 years; IQR 62.08; 73.98) with COPD exacerbation received 14 days of standard therapy at a climatic health resort located at 1,342 m above sea level. HRV was assessed on admission and after 10 days using the “Varicard 2.51” system during an orthostatic test.

   Results. On admission, all patients exhibited reduced heart rate variability and diminished total autonomic regulatory effect on circulation. This pattern persisted in the majority (n = 24) after treatment, and postural responses remained blunted. However, in 9 patients (27.3 %), treatment resulted in increased HRV indices (MxDMn, CV), enhanced parasympathetic activity (RMSSD, pNN50), greater total autonomic modulation (SDNN), and reduced regulatory strain (stress index, SI). Their autonomic status shifted from a state of overstrain (PARS [Index of Regulatory System Activity] = 7.0 points) to
functional tension (PARS = 4.5 points), characteristic of adaptive–compensatory processes. In contrast, 24 patients (72.7 %) developed rigid heart rhythm with further HRV deterioration post-treatment.

   Conclusion. Positive HRV dynamics following therapy were observed in only 27.3 % of patients; no significant improvement occurred in the remaining 72.7 %. This lack of response is likely due to incomplete acclimatization, influenced by individual functional capacities and specific adaptive reactions. Therefore, extending the duration of inpatient stays in middle-mountain settings appears necessary to achieve full physiological adaptation in COPD patients. Identifying predictors of heightened sensitivity to high-altitude climatotherapy may provide deeper insights into COPD pathophysiology and personalized therapeutic approaches.

1. Global initiative for chronic obstructive lung disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. 2025 Report. Available at: https://goldcopd.org/2025-gold-report-2/

2. [Chronic obstructive pulmonary disease. Clinical guidelines 2021] (in Russian). Available at: https://diseases.medelement.com/disease-хроническая-обструктивная-болезнь-легких-кр-рф-2024/18404#attachments

3. Kulik E.G., Pavlenko V.I., Naryshkina S.V. [Biochemical predictors of preclinical arteriosclerosis in patients with chronic obstructive pulmonary disease after COVID-19]. Bulleten' fiziologii i patologii dyhania = Bulletin Physiology and Pathology of Respiration 2023; 91:34–40 (in Russian). doi: 10.36604/1998-5029-2024-91-34-40

4. Nevzorova V.A. Brodskaya T.A., Zakharchuk N.V. [COPD and Hypertension: leading links of the cardiopulmonary continuum]. Vladivostok: Meditsina DV; 2023 (in Russian). ISBN: 9785983012776.

5. Huang K., Zheng Z., Li W., Niu H., Lei J., Dong F., Yang T., Wang C. Sociodemographic correlates with prevalence of comorbidities in patients with chronic obstructive pulmonary disease: a study from a Chinese National Survey. Lancet Reg. Health West Pac. 2023; 42:100937. doi: 10.1016/j.lanwpc.2023.100937

6. Aisanov Z.R., Chuchalin A.G., Kalmanova E.N. [Chronic obstructive pulmonary disease and cardiovascular comorbidity]. Kardiologiya = Kardiologiia 2019; 59(8S):24–36 (in Russian). doi: 10.18087/cardio.2572

7. Karnati S., Seimetz M., Kleefeldt F., Sonawane A., Madhusudhan T., Bachhuka A., Kosanovic D., Weissmann N., Krüger K., Ergün S. Chronic obstructive pulmonary disease and the cardiovascular system: vascular repair and regeneration as a therapeutic target. Front. Cardiovasc. Med. 2021; 8:649512. doi: 10.3389/fcvm.2021.649512

8. World Health Organization. Noncommunicable diseases country profiles. 2018. Available at: https://www.who.int/nmh/publications/ncd-profiles-2018/en.

9. Miller J., Edwards L., Agustí A., Bakke P., Calverley P.M., Celli B., Coxson H.O., Crim C., Lomas D.A., Miller B.E., Rennard S., Silverman E.K., Tal-Singer R., Vestbo J., Wouters E., Yates J.C., Macnee W. Evaluation of COPD longitudinally to identify predictive surrogate endpoints (ECLIPSE) investigators. comorbidity, systemic inflammation and outcomes in the ECLIPSE cohort. Respir. Med. 2013; 107(9):1376–1384. doi: 10.1016/j.rmed.2013.05.001

10. Nevzorova V., Brodskaya T., Zakharchuk N. Smocking, respiratory diseases and endothelial dysfunction. In: Lenasi H., editor. Endothelial dysfunction – old concepts and new challenges. London: IntechOpen; 2018. doi: 10.5772/intechopen.73555

11. Yabluchansky N.I., Kantor B.Ya., Martynenko A.V., Pityk A.I. [Heart rate variability in the clinic]. Khar'kov: Osnova; 2001 (in Russian).

12. Baevsky R.M., Ivanov G.G., Gavrilushkin A.P., Dovgalevsky P.Ya., Kukushkin Yu.A., Mironova T.F., Prilutsky D.A., Semenov A.V., Fedorov V.F., Fleishman A.N., Medvedev M.M., Chireikin L.V. [Analysis of heart rate variability when using various electrocardiographic systems (part 1)]. Vestnik aritmologii = Journal of Arrhytmology 2002; 24:65–86 (in Russian). EDN: HSPLXF.

13. Kuzmenko N.V., Tsyrlin V.A., Pliss M.G. [To the interpretation of frequency components of the heart rate variability]. Translyatsionnaya meditsina = Translational Medicine 2021; 9(3):35–58 (in Russian). doi: 10.18705/2311-4495-2022-9-3-35-58

14. Abrosimov V.N., Kosyakov A.V., Ponomareva I.B., Peregudova N.N. [New approaches to assessing the functional status of patients with chronic obstructive pulmonary disease]. Pulmonologiya = Pulmonology 2020; 30(1):53–60 (in Russian). doi: 10.18093/0869-0189-2020-30-1-53-60

15. Kubincová A., Takáč P., Demjanovič Kendrová L., Joppa P. Predictors of quality-of-life improvement at different minimum clinically important difference values in patients with chronic obstructive pulmonary disease after climatic rehabilitation treatment. Life (Basel) 2023; 13(8):1763. doi: 10.3390/life13081763

16. Vinnikov D., Khafagy A., Blanc P.D., Brimkulov N., Steinmaus C. High-altitude alpine therapy and lung function in asthma : systematic review and meta-analysis. ERJ Open Res. 2016; 2(2):00097-2015. doi: 10.1183/23120541.00097-2015

17. Gvozdjaková A., Sumbalova Z., Kucharska J., Rausova Z., Kovalˇcíková E., Takacsova T., Navas P., Lopez-Lluch G., Mojto V., Palacka P. Mountain spa rehabilitation improved health of patients with post-COVID-19 syndrome: pilot study. Environ. Sci. Pollut. Res. 2022; 30(6):14200–14211. doi: 10.1007/s11356-022-22949-2

18. Sumbalova Z., Kucharska J., Rausova Z., Palacka P., Kovalciková E., Takacsova T., Mojto V., Navas P., Lopez-Lluch G., Gvozdjakova A. Reduced platelet mitochondrial respiration and oxidative phosphorylation in patients with post COVID-19 syndrome are regenerated after spa rehabilitation and targeted ubiquinol therapy. Front. Mol. Biosci. 2022; 9:1016352. doi: 10.3389/fmolb.2022.1016352

19. Kappen J.H., In't Veen J.C.C.M., Braunstahl G.J. High-altitude treatment in severe asthma: Effective and needed in an era of precision medicine. Neth. J. Med. 2018; 76(5):205–206.

20. Hashimoto S., Rijssenbeek-Nouwens L.H., Fieten K.B., Weersink E.J., Bel E.H. Predictors of benefit from high-altitude climate therapy in adults with severe asthma. Neth. J. Med. 2018; 76(5):218–225.

21. Boksha V.G. [Handbook of Climatotherapy]. Kyiv, Zdorovya, 1989 (in Russian). ISBN 5-311-00337-5.

22. Kiselev A.R., Arablinsky N.A., Mironov S.A., Umetov M.A., Berns S.A., Yavelov I.S., Drapkina O.M. [Physiological and pathophysiological aspects of short-term middle-altitude adaptation in humans]. Kardiovaskulayrnaya terapiya i profilaktika = Cardiovascular Therapy and Prevention 2022; 21(8):97–105 (in Russian). doi: 10.15829/1728-8800-2022-3306

23. Shaffer F., Ginsberg J.P. An overview of heart rate variability metrics and norms. Front. Public Health. 2017; 5:258. doi: 10.3389/fpubh.2017.00258

24. Datieva F.S., Belyaeva V.A., Dzampaeva Zh.V., Takoeva E.A., Nartikoeva M.I., Datieva L.R. [Dysregulatory aspects in the pathogenesis of cardiovascular disorders. Possibilities of correction with phytoadaptogens: experimental and clinical studies]. Vladikavkaz: IP Tsopanova A.Yu.; 2022 (in Russian). ISBN: 978-5-00081-526-7.

25. Fleishman A.N. [Heart rate variability and slow hemodynamic oscillations. Nonlinear phenomena in clinical practice]. Novosibirsk: Isdatel'stvo SO RAN; 2009 (in Russian). ISBN: 978-5-7692-1079-2.

26. Shlyk N.I. [Heart rate variability and methods for its determination in athletes during the training process: a methodological guide]. Izhevsk: Udmurskiy gosudarstvennyy universitet; 2022 (in Russian). EDN: YPJKKY.

27. Jensen-Urstad K., Storck N., Bouvier F., Ericson M., Lindblad L.E., Jensen-Urstad M. Heart rate variability in healthy subjects is related to age and gender. Acta Physiol. Scand. 1997; 160(3):235–241. doi: 10.1046/j.1365-201X.1997.00142.x

28. Rabe K.F., Hurst J.R., Suissa S. Cardiovascular disease and COPD: dangerous liaisons? Eur. Respir. Rev. 2018; 27(149):180057. doi: 10.1183/16000617.0057-2018. Erratum in: Eur. Respir. Rev. 2018; 27(150):185057. doi: 10.1183/16000617.5057-2018

29. Lu W., Aarsand R., Schotte K., Han J., Lebedeva E., Tsoy E., Maglakelidze N., Soriano J.B., Bill W., Halpin D.M.G., Rivera M.P., Fong K.M., Kathuria H., Yorgancıoğlu A., Gappa M., Lam D.C., Rylance S., Sohal S.S. Tobacco and COPD: presenting the World Health Organization (WHO) Tobacco Knowledge Summary. Respir. Res. 2024; 25(1):338. doi: 10.1186/s12931-024-02961-5

30. Martínez-Gestoso S., García-Sanz M.T., Carreira J.M., Salgado F.J., Calvo-Álvarez U., Doval-Oubiña L., Camba-Matos S., Peleteiro-Pedraza L., González-Pérez M.A., Penela-Penela P., Vilas-Iglesias A., González-Barcala F.J. Impact of anxiety and depression on the prognosis of COPD exacerbations. BMC Pulm. Med. 2022; 22(1):169. doi: 10.1186/s12890-022-01934-y. Erratum in: BMC Pulm. Med. 2022; 22(1):213. doi: 10.1186/s12890-022-01999-9

31. Barutcu I., Esen A.M., Kaya D., Turkmen M., Karakaya O., Melek M., Esen O.B., Basaran Y. Cigarette smoking and heart rate variability: dynamic influence of parasympathetic and sympathetic maneuvers. Ann. Noninvasive Electrocardiol. 2005; 10(3):324–329. doi: 10.1111/j.1542-474X.2005.00636.x

32. Barantke M., Krauss T., Ortak J., Lieb W., Reppel M., Burgdorf C., Pramstaller P.P., Schunkert H., Bonnemeier H. Effects of gender and aging on differential autonomic responses to orthostatic maneuvers. J. Cardiovasc. Electrophysiol. 2008; 19(12):1296–1303. doi: 10.1111/j.1540-8167.2008.01257.x

33. Milashchenko A.I., Andreev A.N., Mironov V.A., Popov A.A., Mironova T.F. [The assessment of heart rate variability by rhythmocardiography in patients with chronic obstructive pulmonary disease]. Ural'skiy meditsinskiy zhurnal = Ural Medical Journal 2020; 07(190):60–63. doi: 10.25694/URMJ.2020.07.40

34. Tseng C.Y., Chang J.C., Chen Y.C., Huang H.H., Lin C.S., How C.K., Yen D.H. Changes of heart rate variability predicting patients with acute exacerbation of chronic obstructive pulmonary disease requiring hospitalization after ED treatment. J. Chin. Med. Assoc. 2018; 81(1):47–52. doi: 10.1016/j.jcma.2017.10.003

35. Alqahtani J.S., Aldhahir A.M., Alghamdi S.M., Al Ghamdi S.S., Al Draiwiesh I.A., Alsulayyim A.S., Alqahtani A.S., Alobaidi N.Y., Al Saikhan L., Al Rabeeah S.M., Alzahrani E.M., Heubel A.D., Mendes R.G., Alqarni A.A., Alanazi A.M., Oyelade T. A systematic review and meta-analysis of heart rate variability in COPD. Front. Cardiovasc. Med. 2023; 10:1070327. doi: 10.3389/fcvm.2023.1070327

36. Wu D.W., Chang L.H., Yang P.C., Kuo T.Y., Tsai D.L., Chen H.C., Yuan H.L., Chen P.S., Chen S.C., Lin I.M. Anxiety is a mediator between heart rate variability and quality of life in chronic obstructive pulmonary disease. J. Pers. Med. 2022; 12(6):960. doi: 10.3390/jpm12060960

37. Markov A., Solonin I., Bojko E. Heart rate variability in workers of various professions in contrasting seasons of the year. Int. J. Occup. Med. Environ Health. 2016; 29(5):793–800. doi: 10.13075/ijomeh.1896.00276

38. MacDonald D.M., Mkorombindo T., Ling S.X., Adabag S., Casaburi R., Connett J.E., Helgeson E.S., Porszasz J., Rossiter H.B., Stringer W.W., Voelker H., Zhao D., Dransfield M.T., Kunisaki K.M. Heart rate variability on 10-second electrocardiogram and risk of acute exacerbation of COPD: A secondary analysis of the BLOCK COPD trial. Chron. Obstr. Pulm. Dis. 2022; 9(2):226–236. doi: 10.15326/jcopdf.2021.0264

39. Yusupalieva M.M., Yusupaliev A.U. [The climatotherapy of depressive states in patients with chronic obstructive pulmonary disease]. Zhurnal nevrologii i gsichiatrii imeny S.S. Korsakova = S.S. Korsakov Journal of Neurology and Psychiatry 2016; 116(11):106–109 (in Russian). doi: 10.17116/jnevro2016116111106-109

40. Schwarz E.I., Latshang T.D., Furian M., Flück D., Segitz S., Müller-Mottet S., Ulrich S., Bloch K.E., Kohler M. Blood pressure response to exposure to moderate altitude in patients with COPD. Int. J. Chron. Obstruct. Pulmon. Dis. 2019; 14:659–666. doi: 10.2147/COPD.S194426