Jesper Kristiansen The National Research Centre for the Working Environment, Denmark

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1 Mental workload, overload and heart rate variability Jesper Kristiansen The National Research Centre for the Working Environment, Denmark

2 Objectives After the presentation you will: Have a basic understanding of the physiology behind HRV Have knowledge of commonly used HRVderived measures in studies of mental stress, Know which factors other than mental stress that influence HRV, Understand how mental stress is reflected in measures of autonomic regulation that can be derived from HRV.

3 1. HRV basics

4 HRV = Heart rate variability The cardiac conduction system (from: Levick (2003). An Introduction to Cardiovascular Physiology, 4th ed.) RR-interval Electrocardiogram (ECG) P Q R S T

5 Regulation of HR Intrinsic heart rate of the denervated heart is almost constant and around 100 bpm. Control Cardiac transplant patient Sands et al (1989). Circulation 79:

6 Regulation of HR The decaying membrane potential of pacemaker cells in the sino-atrial node is the basis for regulation of HR. i K : potassium current; i f : funny current (mainly Na + ); i Ca,T : Transient Ca 2+ channel current; i Ca,L : Long-lasting Ca 2+ channel current. * : Pacemaker potential Levick (2003). An Introduction to Cardiovascular Physiology, 4th ed.

7 Central control of the heart rate The cardiovascular center is located in the Medulla oblangata. Input to cardiovascular center: From higher brain centers (cerebral cortex, limbic systems, and hypothalamus) From sensory receptors (baroreceptors, chemoreceptors, proprioceptors) Output to the heart: Increased rate of spontaneous depolarizations in SA (AV) node Increased contractility of atria and ventricles Decreased rate of spontaneous depolarizations in SA (AV) node

8 ANS regulation of HR Sympathetic noradrenaline (NAd) binds to 1 -adrenergic receptors on myocardial pacemaker cells activates adenylate cyclase Parasympathetic acetylcholine (ACh) binds to M2-muscarinic receptors inhibits adenylate cyclase. 2nd messenger (slow) Levick (2003). An Introduction to Cardiovascular Physiology, 4th ed.

9 ANS regulation of HR Parasympathetic acetylcholine (ACh) opens K Ach channel hyperpolarizes the membrane potential. No 2nd messenger (fast) Levick (2003). An Introduction to Cardiovascular Physiology, 4th ed.

10 ANS regulation of HR HR responses to PVN stimulation in rats High frequency range Stauss et al (1997). Am J Physiol 273: H

11 2. Measures used in HRV studies

12 R-R interval variability measures Tachogram: R-R intervals ECG

13 R-R interval variability measures The tachogram Segment or epoch, length depends on the study from few min >24 hr) You can not compare HRV calculated for different epoch lengths!

14 R-R interval variability measures HRV: The variability of all N-N intervals (e.g., SDNN) Other ECG-derived measures: Measures of the power N-N interval variability at different frequencies (e.g., HF power, LF power, RMSSD) Measures describing other aspects of the N-N interval variability (chaotic, randomness etc.) (e.g., ApE) Other measures derived from the ECG (e.g., heart rate turbulence).

15 Time domain measures Time domain measures express variability by SD or nonparametric measures Variable (units) Definition Interpretation SDNN (ms) Standard deviation of all N-N intervals Total variability (HRV) SDANN (ms) SDNN index (ms) RMSSD (ms) pnn50 (%) The standard deviation of all 5 min epoch averages of N-N intervals. The average of the standard deviations of N-N intervals in all 5 min epochs. The square root of the mean of squared differences of successive N-N intervals Percentage of all successive N-N intervals with length larger than 50 ms. Low frequent modulation of HR Low frequent modulation of HR High frequent modulation of HR High frequent modulation of HR

16 Frequency domain measures Frequency domain measures extracts frequency information by Fast Fourier Transformation analysis (FFT) or autoregressive modelling

17 HRV power spectrum FFT Autoregressive model VLF LF HF

18 Frequency domain measures Variable (units) Definition Interpretation Total power (ms 2 ) Total area under the power density function ( Hz) Total variability (HRV), equal to (SDNN) 2 HFP or HF (ms 2 ) LFP og LF (ms 2 ) VLF (ms 2 ) Area under the power density function in the frequency range Hz Area under the power density function in the frequency range Hz Area under the power density function in the frequency range Hz Parasympathetic modulation of HR (respiratory sinus arrythmia) Sympathetic modulation of HR with contribution from parasympathetic activity Modulation of HR by slow blood pressure regulating systems HF n.u. (normalized units) HF/(TP-VLF) Same as HF LF n.u. (normalized units) LF/(TP-VLF) Same as LF LF/HF LF/HF Autonomic balance, i.e. the balance between sympatethic and parasympathetic activity.

19 Time domain vs. frequency domain Many measures strongly correlated (e.g., SDNN total power, RMSSD HF, RMSSD pnn50 etc.) Difficult to interpret frequency components of HR for long segments (VLF and ULF dominates the power spectrum) The estimation of the power spectrum require stationarity of the signal Power spectrum analysis: 5 min segments are preferred (down to 2 min possible for HF only!). Task force (1996). Heart rate variability. Standards of measurement, physiological interpretation and clinical use. Circulation 93:

20 3. Origins of HRV

21 Respiratory sinus arrythmia (RSA) Fast heart rate (tachycardia) during inspiration Slow heart rate (bradycardia) during expiration. The freqency of the HF component is entrained to the respiration frequency

22 Respiratory sinus arrythmia The exact mechanism causing RSA is not known, but central are: variation of venous return the heart (preload) caused by the respiratory pump, in combination with reflexes that control HR (Bainbridge reflex and baroreceptor reflexes) RSA is therefore an index of the gain of the baroreceptor cardiac vagal reflex responses. Barnardi et al. (2001). Modulatory effects of respiration. Auton Neurosci Basic Clin 90: 47-56

23 10s fluctuations in HR 10 s

24 10s fluctuations in HR Oscillations caused by resonance between HR and different blood pressure regulating systems, e.g.: baroreceptor reflex renin-angiotensin system local endothelial NO system Afferent nerve signal from these blood pressure regulating systems are integrated in the CNS. The HR is result of the balance between efferent nerve traffic from sympathetic and parasympathetic nerves (sympatho-vagal balance).

25 Frequency domain measures HF spectral power is modulated by parasympathetic activity only LF spectral power is modulated by both sympathetic and parasympathetic activity LF/HF reflects sympathovagal balance.

26 Summary: HRV measures HRV is derived from analysis of (normal) R-R intervals, e.g., recorded from an ECG HR oscillates with many frequencies (complex pattern in tachogram) that reflects the influence of different blood pressure systems Rapid fluctuations (HF, Hz) is caused by vagal activity Slow fluctuations (LF, Hz) is caused by a mixture of sympathetic and vagal activity. Slower fluctations is caused by even slower regulatory systems (e.g., temperature fluctations, day-night periodicity).

27 4. Factors that influence HRV

28 Body posture and HRV Supine rest After head up tilt LF/HF = 1.06 LF/HF = 3.66

29 Physical exercise and HRV Spectral components do not estimate sympatho-vagal interactions during exercise (Perini & Veicsteinas, 2003). Left panels: Filled symbols: Sedentary subjects. Open symbols: Athletes. Perini & Veicsteinas (2003). Heart rate variability and autonomic activity at rest and during exercise in various physiological conditions. Eur J Appl Physiol 90:

30 Physical exercise and HRV Regulation of HR during exercise depends on: Size of the active muscle mass Type of exercise (single bout, repeated, static vs. dynamic) Intensity of the exercise Body position during exercise.

31 HRV and gender Low frequency components of HRV are lower, and high frequency components higher, in women compared men Crude and adjusted mean values (± SD) of LF, HF and total power in men and women. Kuch et al., (2001). Determinants of short-term heart rate variability in the general population. Cardiol 95:

32 HRV and HR, age LF and HF decrease with increase in HR and age Regression coefficients (b) and partial R2 values of factors related to LF and HF power in forward stepwise regression model Kuch et al., (2001). Determinants of short-term heart rate variability in the general population. Cardiol 95:

33 HRV has a diurnal rhythm Low frequency components of HRV are lower, and high frequency components higher, at night compared to day Raemaker et al. (1998). Heart rate variability and heart rate in health volunteers. Eur Heart J 19:

34 5. Mental demands and HRV

35 HRV and mental challenge Increase in LF n.u. and a decrease in HF n.u. during color-word test (CWT) compared to rest condition. I SNS = LF normalized; I PNS = HF normalized Garde et al. (2002). Effects of mental and physical demands on heart rate variability during computer work. Eur J Appl Physiol 87:

36 HRV and mental challenge Decrease in HF n.u. and increase in LF/HF during computerbased drawing task under time pressure (M-works) and logical reasoning task compared to rest condition. HF (normalized units) LF/HF HF n.u LF/HF Rest1 M-works Reasoning Rest2 Conditions: Silent Task Office background noise (65 dba) 0 Rest1 M-works Reasoning Rest2 Task (unpublished results)

37 Mental work stress and HRV Study design challenges: Which (5 min) periods should you look at? How do you take into account (control) the effect of body posture physical activity level social interactions, etc?

38 Work stress and HRV Effects of work stress on ambulatory blood pressure, heart rate, and heart rate variability. Vrijkotte TGM. Van Doornen LJP, de Geus EJC. Hypertension 2000; 35: Research questions: Are the adverse health effects of work stress mediated by increased blood pressure? How does effort-reward imbalance and overcommitment affect blood pressure, heart rate and vagal tone?

39 Work stress and HRV Low RMSSD in white-collar workers with high effort-reward imbalance compared to workers with low imbalance difference continues on non-workday RMSSD Low imbalance ( ;n=86) High imbalance ( ; n=23) work leisure sleep work leisure sleep leisure sleep Non-workday Vrijkotte et al. (2000). Effects of works stress on ambulatory blood pressure, heart rate, and heart rate variability. Hypertension 35:

40 Work stress and HRV 90 Heart rate (BPM) High imbalance ( ; n=23) Low imbalance ( ;n=86) 60 work leisure sleep work leisure sleep leisure sleep Non-workday Vrijkotte et al. (2000). Effects of works stress on ambulatory blood pressure, heart rate, and heart rate variability. Hypertension 35:

41 Work stress and HRV Low RMSSD associated with increased probability of mild hypertension. Vrijkotte et al. (2000). Effects of works stress on ambulatory blood pressure, heart rate, and heart rate variability. Hypertension 35:

42 Work stress and HRV Selection of sampling periods HRV sampled from: 1) 3 x 24 hr (2 workdays + 1 non-workday) 2) Subjects was wearing motility monitors 3) Every day divided into work (workdays only), leisure and sleep. HRV diary 1) Dairy filled in every 30 min (approximately) 2) Body posture (upright, sitting, reclining) 3) Activities (sitting, standing, walking). Vrijkotte et al. (2000). Effects of works stress on ambulatory blood pressure, heart rate, and heart rate variability. Hypertension 35:

43 HRV and work-related stress HF higher in subjects with low job strain 500 Mean High Frequency Power After Dinner Before Dinner Afternoon at Work Lunch Morning at Work Sleep After Dinner Before Dinner Afternoon on Rest Da Lunch Morning on Rest Day Awake on Rest Day Sleep Job Strain Awake Low High Sociological Period Collins, Karasek & Costas (2005). Job strain and autonomic indices of cardiovascular disease risk. Am J Ind Med 48:

44 HRV and work-related stress Sympathetic indices (incl. LF/HF) increase with strain at work but not with overall strain. Collins, Karasek & Costas (2005). Job strain and autonomic indices of cardiovascular disease risk. Am J Ind Med 48:

45 HRV and work-related stress Selection of sampling periods HRV sampled from: 1) 2 x 24 hr (work day + rest day) 2) Each day divided into sociological periods (start of work, after lunch, end of work, at home after dinner, sleep) 3) Mental challenge situation. HRV diary 1) Dairy filled at the end of every sociological period 2) Body posture (upright, sitting, reclining), location (work, home etc.) 3) Activity (physical exertion, social interactions) 4) Questions on decision lattitude, psychological demands. Collins, Karasek & Costas (2005). Job strain and autonomic indices of cardiovascular disease risk. Am J Ind Med 48:

46 HRV and work-related stress Stress management at the worksite. Reversal of symptoms profile and cardiovascular dysregulation. Lucini D, Riva S, Pizzinelli P, Pagani M. Hypertension 2007; 49: Research questions: Is work-related stress associated with altered regulation of the autonomic nervous system (ANS)? Can stress symptoms and ANS deregulation be alleviated by implementing a stress management program?

47 HRV and work-related stress White-collar workers in company during downsizing (stressor) (n=91) and controls (n=79). Average values for LF and HF at rest and standing induced changes.

48 HRV and work-related stress White-collar workers in company during downsizing (stressor) (n=51). Effect of a stress-management program (SMP, n=26) versus sham program (SP=25) on HRV Lucini, Riva, Pizzinelli, Pagani (2007). Stress management at the worksite. Reversal of symptoms profile and cardiovascular dysregulation. Hypertension 49:

49 Summary Increase in LF and decreases HF consistently found in laboratory mental challenge experiments: mental arithmetics, color-word test, logical reasoning, drawing under time pressure etc. Work stress is associated with increase in sympathetic HRV measures, and decrease in parasympathetic measures. Autonomic changes caused by work stress are sustained during the non-workday (e.g., Vrijkotte et al. (2000), Collins et al. (2005)) or during the night of the workday (Mitani et al Int Arch Occup Environ Health 79: 27-32) Autonomic changes caused by work stress can be reversed by stress management (Lucini et al. (2007). Hypertension 49: )

50 Thank you for your attention!

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