Comprehensive viewpoints on heart rate variability at high altitude

Figures & data

Figure 1. Traceability of HRV.

Table 1. Analysis method of HRV.

Analysis method		Measure method	Significance	Reference Indicators
Linear analysis	Time domain analysis (5,15,25)	Specific values of the R-R interval of sinus rhythm in chronological order	Evaluate the regulation of autonomic nerve on heart rate	SDNN, CVNN, RMSSD, NN50/pNN50, Triangle index, Histogram analysis
	Frequency domain analysis (15,26)	Calculate the power density spectrum of heart rate variability signals using mathematical transformation methods such as fast Fourier transform or autoregressive modeling	To observe the functional changes of Sympathetic nervous system and Vagus nerve to make up for the shortcomings of time-domain analysis	LF, HF, LF/HF
Nonlinear analysis	Poincar é diagram analysis (27–29)	Combining Geometry and Data Analysis	Can achieve visualization of biological signals	＼
	Approximate entropy analysis (27–29)	Calculate the approximate entropy using a formula	The higher the approximate entropy value, the more complex the changes are, used to evaluate the complexity of biological signals	＼
Seismic electrocardiogram		A noninvasive technique for recording and analyzing cardiac activity by measuring precordial acceleration (31)	Assisted diagnosis for cardiac intervention, atrial fibrillation detection, heart failure, and myocardial ischemia	＼
Gyroscopic electrocardiogram		Analyze the mechanical activity and cardiac function of the heart by collecting and analyzing changes in chest angular velocity related to cardiac activity (31)	Provide evidence for auxiliary diagnosis of cardiovascular diseases such as Atrial fibrillation, Coronary artery disease, acute compensatory heart failure, etc	＼

Figure 2. High altitude hypoxia-related diseases.

The diagram illustrates cardiovascular diseases, respiratory system and endocrine system diseases associated with high altitude hypoxia, the cardiovascular diseases include hypertension, cardiac hypertrophy, pulmonary hypertension, atrial fibrillation, myocardial infarction, and respiratory diseases include high altitude pulmonary edema and obstructive sleep apnea syndrome, endocrine system diseases include hypothyroidism and type 2 diabetes.

Table 2. Relationship between high altitude hypoxia related diseases and HRV.

System	Diseases	Mechanism	HRV Changes
Circulatory	Hypertension (72–80)	Decreased vascular compliance, sympathetic excitation, and cardiac organic damage	The frequency decreased significantly
	Supraventricular arrhythmia and atrial fibrillation caused by pulmonary hypertension (81–86)	Long-term low pressure and hypoxia activate sympathetic, causing changes in cardiac rhythm and autonomic tone	Increased LF and LF/HF, decreased HF in patients
	Myocardial infarction (87–90)	Hypertension, long-term coronary artery spasm	ST segment specific elevation, LF/HF ratio decreased
	Cardiomyopathy (91)	Under the stimulation of high altitude hypoxia, mitochondria may undergo autophagy and certain inflammatory mediators are activated, such as NLRP3 inflammasome	Both LF and HF are significantly suppressed and the amplitude of the QRS complex attenuates instantaneously
Other systems	High altitude pulmonary edema(92–96)	Increased pulmonary artery pressure, coupled with acute hypoxia, lead to changes in autonomic nervous function, decreased heart rate and oxygen saturation, ventricular diastolic dysfunction.	HRV decreases, LF/HF increases
	Obstructive sleep apnea syndrome (97–102)	Endothelial dysfunction, sympathetic activation, increased oxidative stress	With the prolongation of RR interval, LF/HF also decreased significantly
	Diabetes106	\	Low HF and LF
	Hypothyroidism (103)	\	Ectopic pulsation, heart rate changes, RR interval changes

Remarks: HF = high frequency, LF = low frequency.

Table 3. Effects of anti-altitude sickness drugs on HRV.

Classification	Drugs	Research object	indicators
Chinese medicine	Rhodiola rosea	Patients with acute coronary syndrome (97)	SDNN, SDANN, RMSSD ↑
		Elderly patients with unstable angina pectoris (98)	SDNN, SDANN, RMSSD, PNN50 ↑
		Exhausted training rats (110)	TP, LF, HF, LF/HF ↑
	Salvia miltiorrhiza polyphenol acid	Elderly patients with coronary heart disease (100)	HF ↑,LF, LF/HF ↓
	Compound Salvia miltiorrhiza injection	Patients with chronic heart failure (101)	SDNN, SDANN, RMSSD, PNN50 ↑
	Buqi Zhitong decoction	Patients with stable angina pectoris (102)	SDNN, SDANN, SDNN, RMSSD, PNN50 ↑
	Tongluo Anxin decoction	Patients with unstable angina pectoris of coronary heart disease (103)	SDNN ↑
Western medicine	Acetazolamide	Patients with acute mountain sickness (106)	NN50, PNN50, HF ↑
		Patients with central apnea caused by opiate abuse (107)	LF, LF/HF ↓
	Metoprolol	Patients with miocardial infraction (108)	SDRR, SDANN, RMSSD, PNN50, TP, LFP, HFP, HF ↑，LF/HF ↓
		Patients with essential hypertension (109)	RRI, LF variability, HF variability ↑
		Patients with coronary disease (111)	SDNN, HRVTI, LF, HF, TP ↑，LF/HF, VLF ↓
	Trimetazidine	Patients with ischemic heart failure (112)	SDNN, SDANN ↑
		Patients with acute coronary syndrome (113)	SDNN, SDANN, RMSSD, PNN50, HF ↑，LF, LF/HF ↓
		Patients with coronary heart disease after percutaneous coronary intervention (114)	RMSSD, SDSD, PNN50, HF ↑ SDNN, LF, LF/HF ↓
		Patients with acute myocardial infarction (114)	SDSD, RMSSD, HF ↑ LF/HF ↓
		Left ventricular ejection fraction LVEF ≤ 40% in patients with old myocardial infarction and in patients with type 2 diabetes mellitus (115)	SDNN, SDANN, Triangular-index ↑
		Patients with ischemic cardiomyopathy (116)	SDNN, SDANN, RMSSD, PNN50 ↑
		Patients with chronic heart failure (117)	SDNN, SDANN, RMSSD, PNN50 ↑
		Patients with non ST segment elevation acute coronary syndrome	SDNN, SDANN, RMSSD, PNN50 ↑ LF, LF/HF ↓
	Nifedipine	Patients with acute hypertension (118)	LF/HF ↑，HF ↓
		Patients with hypertensive coronary heart disease (119)	LF ↓
		Patients with chronic heart failure and ventricular arrhythmia (120)	SDNN, SDANN, RMSSD, PNN50 ↑
		Patients with essential hypertension (121)	LF/HF ↑ SDNN, RMSSD, PNN50 ↑，LF/HF ↓
Chinese medicine combined with western medicine	Metoprolol combined with nifedipine	Patients with systematic hypertension (122)	RRI, SDNN, LFP, HFP ↑,LF/HF ↓
		Patients with essential hypertension (123)	SDNN, SDANN, RMSSD ↑
		Patients with hypertension with coronary heart disease (124)	SDNN, SDANN, RMSSD, PNN50 ↑
	Metoprolol combined with Belopril	Patients with chronic heart failure (125)	SDNN, SDANN, SDNN index, RMSSD, PNN50 ↑
		Elderly patients with essential hypertension with chronic heart failure (42)	SDNN, SDANN, RMSSD, PNN50 ↑
	Metoprolol combined with trimetazidine	Patients with unstable angina pectoris (126)	SDNN, SDANN, RMSSD, PNN50 ↑
		Patients with stable angina pectoris (127)
		Patients with acute myocardial infarction (128)
	Metoprolol combined with Wenxin granule	Patients with acute myocardial infarction (129)	SDNN, SDANN, PNN50 ↑
	Yindan Xintai Dropping Pills	Patients with supraventricular arrhythmia (130)	SDNN, SDANN, SDNN index, RMSSD, PNN50 ↑
	Ginkgo damole combined with mecobalamin	Patients with diabetic cardiovascular autonomic neuropathy (42)	SDNN, SDANN, RMSSD, PNN50, HF, LF, LF/HF ↑
	Rhodiola rosea combined with levocarnitine	Patients with coronary heart disease with diabetes (131)	SDNN, SDANN, RMSSD, PNN50, LF, HF ↑
	Xinkeshu combined with metoprolol	Young Patients with non organic ventricular premature contraction (132)	SDNN, SDANN, HF ↑，LF ↓

Notes: SDNN=standard deviation of all normal to normal RR intervals, SDANN=standard deviation of all mean 5 minute NN intervals, RMSSD=the root mean square successive differences, PNN50=percentage of adjacent RR intervals more than 50 ms different for the total number of RR intervals, TP=Total power, LF=low frequency, HF=high frequency, NN50=the number of differences between adjacent normal RR intervals higher than 50 ms, SDRR=the standard deviation of the detrended RR intervals, LFP=low-frequency power, HFP=high-frequency power, RRI=RR interval, HRVTI=heart variability time index, SDSD=the standard deviation of differences between adjacent RR intervals, Triangular-index=heart rate variability Triangular-index, VLF=very low frequency.

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

 PubMed Web of Science ®Google Scholar

Electrophysiology, Task Force of the European Society of Cardiology the North A. 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. Circulation. 1996;93(5):1043–65. doi:10.1161/01.CIR.93.5.1043.

 PubMed Web of Science ®Google Scholar

Quintana DS, Alvares GA, Heathers JA. Guidelines for Reporting Articles on Psychiatry and Heart rate variability (GRAPH): recommendations to advance research communication. Transl Psychiatry. 2016;6(5):e803. doi:10.1038/tp.2016.73.

 PubMed Web of Science ®Google Scholar

Heathers JA. Everything Hertz: methodological issues in short-term frequency-domain HRV. Front Physiol. 2014;5:177. doi:10.3389/fphys.2014.00177.

 PubMed Web of Science ®Google Scholar

Mesin L. Estimation of complexity of sampled biomedical continuous time signals using approximate entropy. Front Physiol. 2018;9:710. doi:10.3389/fphys.2018.00710.

 PubMed Web of Science ®Google Scholar

Alkhodari M, Jelinek HF, Werghi N, Hadjileontiadis LJ, Khandoker AH. Investigating circadian heart rate variability in coronary artery disease patients with various degrees of left ventricle ejection fraction. Annu Int Conf IEEE Eng Med Biol Soc. 2020;2020:714–17.

 PubMedGoogle Scholar

Gammoudi N, Ben Cheikh R, Saafi MA, Sakly G, Dogui M. Cardiac autonomic control in the obstructive sleep apnea. Libyan J Med. 2015;10(1):26989. doi:10.3402/ljm.v10.26989.

 PubMedGoogle Scholar

Allemann Y, Rotter M, Hutter D, Lipp E, Sartori C, Scherrer U, Seiler C. Impact of acute hypoxic pulmonary hypertension on LV diastolic function in healthy mountaineers at high altitude. Am J Physiol Heart Circ Physiol. 2004;286(3):H856–62. doi:10.1152/ajpheart.00518.2003.

 PubMed Web of Science ®Google Scholar

Gupta RK, Himashree G, Singh K, Soree P, Desiraju K, Agrawal A, Ghosh D, Dass D, Reddy PK, Panjwani U, et al. Elevated pulmonary artery pressure and brain natriuretic peptide in high altitude pulmonary edema susceptible non-mountaineers. Sci Rep. 2016;6(1):21357. doi:10.1038/srep21357.

 PubMedGoogle Scholar

Ji X. Clinical efficacy of metoprolol tartrate combined with nifedipine in the treatment of essential hypertension. Modern Diagnosis and Treatment. 2020;31(16):3.

 Google Scholar

Zhang W, Si LY. Obstructive sleep apnea syndrome (OSAS) and hypertension: pathogenic mechanisms and possible therapeutic approaches. Ups J Med Sci. 2012;117(4):370–82. doi:10.3109/03009734.2012.707253.

 PubMed Web of Science ®Google Scholar

Qin H, Steenbergen N, Glos M, Wessel N, Kraemer JF, Vaquerizo-Villar F, Penzel T. The different facets of heart rate variability in obstructive sleep apnea. Front Psychiatry. 2021;12:642333. doi:10.3389/fpsyt.2021.642333.

 PubMed Web of Science ®Google Scholar

Khoo MC, Blasi A. Sleep-related changes in autonomic control in obstructive sleep apnea: a model-based perspective. Respir Physiol Neurobiol. 2013;188(3):267–76. doi:10.1016/j.resp.2013.05.017.

 PubMed Web of Science ®Google Scholar

Young T, Palta M, Dempsey J, Peppard PE, Nieto FJ, Hla KM. Burden of sleep apnea: rationale, design, and major findings of the Wisconsin sleep cohort study. WMJ. 2009;108(5):246–49.

 PubMedGoogle Scholar

Young T, Finn L, Peppard PE, Szklo-Coxe M, Austin D, Nieto FJ, Stubbs R, Hla KM. Sleep disordered breathing and mortality: eighteen-year follow-up of the Wisconsin sleep cohort. Sleep. 2008;31(8):1071–78. doi:10.1002/14651858.CD001106.pub3.

 PubMed Web of Science ®Google Scholar

Hoshi RA, Andreao RV, Santos IS, Dantas EM, Mill JG, Lotufo PA, Bensenor IM. Linear and nonlinear analyses of heart rate variability following orthostatism in subclinical hypothyroidism. Med. 2019;98(4):e14140. doi:10.1097/MD.0000000000014140.

 PubMed Web of Science ®Google Scholar

Limberg JK, Dube S, Kuijpers M, Farni KE, Basu A, Rizza RA, Curry TB, Basu R, Joyner MJ. Effect of hypoxia on heart rate variability and baroreflex sensitivity during hypoglycemia in type 1 diabetes mellitus. Clin Auton Res. 2015;25(4):243–50. doi:10.1007/s10286-015-0301-2.

 PubMed Web of Science ®Google Scholar

Lin S, Lin D, Huang K, Zheng Y. Effects of Rhodiola sachalinensis injection on cardiac function, QT dispersion and heart rate variability in patients with acute coronary syndrome. Chin Geriatric Health Care Med. 2012;10(4):2.

 Google Scholar

Du D. Effect of Rhodiola sachalinensis injection on QT dispersion and heart rate variability in elderly patients with unstable angina pectoris. Mod J Integr Chin West Med. 2017;26(7):3.

 Google Scholar

Zhao X. Protective effect and mechanism research of salidroside on cardiac function of exhaustive exercise Rats. Hebei Medical University; 2015.

 Google Scholar

Wang C. Effect of salvia miltiorrhiza polyphenolate on heart rate variability and cardiac function in elderly patients with coronary heart disease. Grassroots Med Forum. 2021;25(17):2.

 Google Scholar

Zeng X. Clinical study of Danshen injection on cardiac function and heart variability in patients with chronic heart failure. Med Forum Mag. 2014;35(1):3.

 Google Scholar

Liang Z. Hospital, H. X. M. G. G., Effect of Buqi Zhitong decoction on exercise test indexes and heart rate variability in patients with stable angina pectoris. Shaanxi Tradit Chin Med. 2013;34(2):144–45. %@ 1000-7369 %L 61-1105/R %W CNKI.

 Google Scholar

Duan M, Xiong Y, Li X. Effect of tongluo anxin decoction on heart rate variability in patients with unstable angina pectoris of coronary heart disease. Res Tradit Chin Med. 2018;31(12):3.

 Google Scholar

Hung PH, Lin FC, Tsai HC, Chao HS, Chou CW, Chang SC. The usefulness of prophylactic use of acetazolamide in subjects with acute mountain sickness. J Chin Med Assoc. 2019;82(2):126–32. doi:10.1097/JCMA.0000000000000014.

 PubMed Web of Science ®Google Scholar

Naghan PA, Raeisi K, Khoundabi B, Foroughi M, Malekmohammad M, Mohebbi M, Bagheri A, Fahimi F. The effect of acetazolamide on the improvement of central apnea caused by abusing opioid drugs in the clinical trial. Sleep Breath. 2020;24(4):1417–25. doi:10.1007/s11325-019-01968-3.

 PubMed Web of Science ®Google Scholar

Kontopoulos AG, Athyros VG, Papageorgiou AA, Papadopoulos GV, Avramidis MJ, Boudoulas H. Effect of quinapril or metoprolol on heart rate variability in post-myocardial infarction patients. Am J Cardiol. 1996;77(4):242–46. doi:10.1016/S0002-9149(97)89386-1.

 PubMed Web of Science ®Google Scholar

Vesalainen RK, Kantola IM, Airaksinen KE, Tahvanainen KU, Kaila TJ. Vagal cardiac activity in essential hypertension: the effects of metoprolol and ramipril. Am J Hypertens. 1998;11(6 Pt 1):649–58. doi:10.1016/S0895-7061(98)00021-1.

 PubMed Web of Science ®Google Scholar

Zhang Q, Lu XN, Sun NL. Effects of Verapamil and metoprolol on heart rate variability in patients with coronary heart disease. Journal of Peking University, Health sciences. 2007;39(6):610–13.

 Google Scholar

Gunes Y, Guntekin U, Tuncer M, Sahin M. The effects of trimetazidine on heart rate variability in patients with heart failure. Arq Bras Cardiol. 2009;93(2):154–58. doi:10.1590/S0066-782X2009000800014.

 PubMed Web of Science ®Google Scholar

Zhang J, He S, Wang X, Wang D. Effect of trimetazidine on heart rate variability in elderly patients with acute coronary syndrome. Pak J Med Sci. 2016;32(1):75–78. doi:10.12669/pjms.321.8378.

 PubMed Web of Science ®Google Scholar

Wang Y, Sun Z, Wang Z, Gai N, Yang T, Zhi G, Wang Y, Xilie L, Li T. Department of Cardiovascular Medicine, P. G. H., Beijing, the pair-matched cross-over study of the effects of the trimetazidine on the heart rate variability/HRV in old myocardial infarcted cases. Chin J Clin Pharmacol. 2002;3(8):188–91.

 Google Scholar

Ma J, Tan Q, Nie X, Zhou M, Wang B, Wang X, Cheng M, Ye Z, Xie Y, Wang D, et al. Longitudinal relationships between polycyclic aromatic hydrocarbons exposure and heart rate variability: Exploring the role of transforming growth factor-beta in a general Chinese population. J Hazard Mater. 2022;425:127770. doi:10.1016/j.jhazmat.2021.127770.

 PubMed Web of Science ®Google Scholar

Ou Y, Department of Cardiology, H. T. P. s. H. Guangxi Zhuang autonomous region, effect of trimetazidine on heart function and heart rate variability in patients with ischemic cardiomyopathy heart failure. China Med Herald. 2012;9(18):90–91. %@ 1673-7210 %L 11-5539/R %W CNKI

 Google Scholar

Dai X, Yang X, Hua W, Yan L, Youwen Y, Dou W, University, Y. H. A. t. T. Effect of trimetazidine on cardiac function and heart rate variability in patients with chronic heart failure. Shandong Med J. 2014;54(4):52–54. %@ 1002-266X %L 37-1156/R %W CNKI

 Google Scholar

Wolk R, Kulakowski P, Ceremuzynski L. Nifedipine and captopril exert divergent effects on heart rate variability in patients with acute episodes of hypertension. J Hum Hypertens. 1996;10(5):327–32.

 PubMed Web of Science ®Google Scholar

Hoshide S, Kario K, Mitsuhashi T, Ikeda U, Shimada K. Is there any difference between intermediate-acting and long-acting calcium antagonists in diurnal blood pressure and autonomic nervous activity in hypertensive coronary artery disease patients? Hypertens Res. 2000;23(1):7–14. doi:10.1291/hypres.23.7.

 PubMed Web of Science ®Google Scholar

Xiang H, Gou H. Department of Gerontology, G. H. o. T. C. M., Sichuan Province, influence of nifedipine sustained-release tablet on hemorheological indexes, central and peripheral arterial pressure and HRV in CHF+ventricular arrhythmia patients. J Cardiovasc Rehabil Med. 2020;29(3):340–45. %@ 1008-0074 %L 35-1193/R %W CNKI.

 Google Scholar

Shen J, College, T. F. A. H. o. Z. U. M. Comparison of clinical effects of nifedipine with different dosage forms in the treatment of hypertension. Diet Health Care. 2019;6(14):70–71.

 Google Scholar

Ylitalo A, Airaksinen KE, Sellin L, Huikuri HV. Effects of combination antihypertensive therapy on baroreflex sensitivity and heart rate variability in systemic hypertension. Am J Cardiol. 1999;83(6):885–89. doi:10.1016/S0002-9149(98)01067-4.

 PubMed Web of Science ®Google Scholar