Reference ranges of circadian variation parameters of cardiac autonomic modulation in healthy employees: The Mannheim Industrial Cohort Studies

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Reference ranges of circadian variation parameters of cardiac autonomic modulation in healthy employees: The Mannheim Industrial Cohort Studies Symposium 1031: Chronobiology Meets Psychophysiology: Revisiting Circadian Rhythms Underlying 24-h Ambulatory Data Dr. Marc N. Jarczok, Ann-Katrin Rohr-Kräutle, Julian F. Thayer, Joachim E. Fischer March 8th 2018

Slide 2 Aim & Methods Ø Aim: to provide age and sex specific reference values of the circadian pattern of HRV in a healthy working population Ø Voluntary on-site health assessment from 21 company sites across Germany (Industrial engineering, manufacturing, pharmaceutical, automobile, aeronautic and electricity companies) Ø Participation rates: 46% - 58% (years 2009 2013) Ø Online questionnaire (e.g. Health behavior, demography, diagnosis) Ø Objectively measured clinical data Ø Blood draw & ambulatory long-term heart rate recording (Suunto T6 Memory Belt at 1000Hz) Ø HRV parameters obtained at the Centre for Neuroscience Research (Trier, Germany) per 5.35-minute segments of IBI

Slide 3 Ø Healthy is defined rigorously. Participants were excluded not indicating explicitly No (vs. Yes, or unknown ) to any of the following conditions: Ø Hypertension, dyslipidemia, hyperglycemia, Ø Respiratory diseases (e.g. Asthma, COPD), Ø Angina pectoris, stroke, infarction, CHD, Ø Depression, burnout, other chronic diseases, cancer and Ø Taking beta blockers Analysis Sample Ø In addition, objectively measured clinical data had to be unobtrusive (Fasting Plasma Glucose, Hba1c, HDL, LDL, TRIG, Blood Pressure) Ø Aim: Get close to the prototypical circadian variation pattern in healthy population

Slide 4 2009-2013 Analysis Sample Recruited N=19,734 With HR-Recording: N=12,418 N=6,880 Included N=5,538 Exclusion Criteria <20h rec. length (N=4,229) >20% missing 5min intervals (N=796) >6 consecutive 5min intervals with artifact rate >5.4%(N=294) Not defined as healthy (N=1,361) 18-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-65 M (79%) 116 441 573 620 646 835 620 401 128 F (21%) 88 198 209 118 176 182 101 73 13

Slide 5 Individual Example of a Cosine Function N= 264 Intervals 24h Mean= 42.9 13.9 msec 5.35 Minute Interval RMSSD Self-reported Sleep period 1x Male Person 20 years BMI 21 Never Smoker Moving Average (local polynomial smoothing function)

Slide 6 Individual Example of a Cosine Function N= 264 Intervals 24h Mean= 42.9 13.9 msec R 2 =51% Cosine function

Slide 7 Individual Example of a Cosine Function N= 264 Intervals 24h Mean= 42.9 13.9 msec Acrophase = 23:45h R 2 =51% Amplitude = 13.7 msec Cosine function MESOR = 44.2 msec

Slide 8 Reference Ranges by Age Group & Sex Ø Expected relationships: Higher ratio in elderly & Men LF/HF ratio Men LF/HF ratio Women

Slide 9 Reference Ranges by Age Group & Sex Ø Expected relationships: Decrease in SDRR by age group Ø Women show diminished profile LF/HF ratio Men SDRR Men SDRR Women

Slide 10 Reference Ranges by Age Group & Sex Ø Expected relationships: Decrease in RMSSD by age group RMSSD Men RMSSD Women

Slide 11 Effect (Hedges s D) of Sex on HRV Parameters Higher in Men Higher in Women Higher in Men Higher in Women Figure 2 from Koenig, Thayer: Sex differences in healthy human heart rate variability: A meta-analysis Neuros. & Biobehav. Reviews 64 (2016)

Slide 12 Effect (Hedges s D) of Sex on HRV Parameters Higher in Men Higher in Women Higher in Men Higher in Women Figure 2 from Koenig, Thayer: Sex differences in healthy human heart rate variability: A meta-analysis Neuros. & Biobehav. Reviews 64 (2016)

Slide 13 ØP-values for Wilcoxon Rank test for sex difference within age group ØSimilar pattern for parametric tests & CI of Hedges s D HRV RR SDRR RMSS RMSSD D HF LF LF/HF TOTAL 18-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-65 Quinquennium 18-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-65 MESOR 0.000 0.000 0.000 0.000 0.000 0.000 0.004 0.005 0.032 Amplitude 0.000 0.000 0.000 0.022 0.000 0.000 1.000 1.000 0.290 Acrophase 0.855 0.990 0.612 0.621 0.462 0.998 1.000 1.000 0.993 MESOR 0.000 0.000 0.000 0.000 0.000 0.000 0.006 0.170 0.795 Amplitude 0.002 0.020 0.632 0.038 0.003 0.294 0.280 0.998 0.826 Acrophase 0.216 0.848 0.452 0.490 0.002 0.006 0.811 0.992 0.709 MESOR 0.001 0.011 0.454 0.840 0.298 0.926 1.000 1.000 1.000 Amplitude 0.025 0.422 0.850 0.211 0.931 0.503 0.894 1.000 0.998 Acrophase 0.990 0.987 0.252 0.963 0.807 0.691 1.000 0.873 1.000 MESOR 0.029 0.717 1.000 1.000 1.000 0.932 0.631 0.715 1.000 Amplitude 0.015 0.989 1.000 0.536 0.999 1.000 0.388 0.923 0.999 Acrophase 1.000 1.000 0.670 1.000 0.980 0.865 0.979 0.881 0.998 MESOR 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.003 0.321 Amplitude 0.000 0.000 0.010 0.000 0.000 0.006 0.422 0.026 0.070 Acrophase 1.000 0.674 0.985 0.981 1.000 1.000 1.000 1.000 0.110 MESOR 0.003 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.330 Amplitude 0.257 0.000 0.000 0.000 0.004 0.000 0.000 0.313 1.000 Acrophase 1.000 0.925 1.000 0.084 0.021 0.001 0.988 0.769 0.983 MESOR 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.158 0.558 Amplitude 0.000 0.001 0.047 0.004 0.000 0.000 0.716 0.919 0.071 Acrophase 0.053 1.000 0.729 0.811 0.093 0.023 0.354 0.732 0.993

Slide 14 ØP-values from ANOVA PostHoc Test testing between age-group differences (Sidak adjusted) RMSSD 1 2 3 4 5 6 7 8 9 SDRR 1 2 3 4 5 6 7 8 9 18-24 (1) 18-24 (1) 25-29 (2) 25-29 (2) 30-34 (3) 30-34 (3) 35-39 (4) 35-39 (4) 40-44 (5) 40-44 (5) 45-49 (6) 45-49 (6) 50-54 (7) 50-54 (7) 55-59 (8) 55-59 (8) 60-65 (9) 60-65 (9) HF 1 2 3 4 5 6 7 8 9 TP 1 2 3 4 5 6 7 8 9 LF 1 2 3 4 5 6 7 8 9 18-24 (1) 18-24 (1) 18-24 (1) 25-29 (2) 25-29 (2) 25-29 (2) 30-34 (3) 30-34 (3) 30-34 (3) 35-39 (4) 35-39 (4) 35-39 (4) 40-44 (5) 40-44 (5) 40-44 (5) 45-49 (6) 45-49 (6) 45-49 (6) 50-54 (7) 50-54 (7) 50-54 (7) 55-59 (8) 55-59 (8) 55-59 (8) 60-65 (9) 60-65 (9) 60-65 (9)

Slide 15 ØP-values for Men from ANOVA PostHoc Test testing between agegroup differences (Sidak adjusted) RMSSD 1 2 3 4 5 6 7 8 9 SDRR 1 2 3 4 5 6 7 8 9 18-24 (1) 18-24 (1) 25-29 (2) 25-29 (2) p<0.05 30-34 (3) 30-34 (3) 35-39 (4) 35-39 (4) 40-44 (5) 40-44 (5) 45-49 (6) 45-49 (6) 50-54 (7) 50-54 (7) 55-59 (8) 55-59 (8) 60-65 (9) 60-65 (9) HF 1 2 3 4 5 6 7 8 9 TP 1 2 3 4 5 6 7 8 9 LF 1 2 3 4 5 6 7 8 9 18-24 (1) 18-24 (1) 18-24 (1) 25-29 (2) 25-29 (2) 25-29 (2) 30-34 (3) 30-34 (3) 30-34 (3) 35-39 (4) 35-39 (4) 35-39 (4) 40-44 (5) 40-44 (5) 40-44 (5) 45-49 (6) 45-49 (6) 45-49 (6) 50-54 (7) 50-54 (7) 50-54 (7) 55-59 (8) 55-59 (8) 55-59 (8) 60-65 (9) 60-65 (9) 60-65 (9)

Slide 16 ØP-values for Women from ANOVA PostHoc Test testing between age-group differences (Sidak adjusted) RMSSD 1 2 3 4 5 6 7 8 9 SDRR 1 2 3 4 5 6 7 8 9 18-24 (1) 18-24 (1) 25-29 (2) 25-29 (2) p<0.05 30-34 (3) 30-34 (3) 35-39 (4) 35-39 (4) 40-44 (5) 40-44 (5) 45-49 (6) 45-49 (6) 50-54 (7) 50-54 (7) 55-59 (8) 55-59 (8) 60-65 (9) 60-65 (9) HF 1 2 3 4 5 6 7 8 9 TP 1 2 3 4 5 6 7 8 9 LF 1 2 3 4 5 6 7 8 9 18-24 (1) 18-24 (1) 18-24 (1) 25-29 (2) 25-29 (2) 25-29 (2) 30-34 (3) 30-34 (3) 30-34 (3) 35-39 (4) 35-39 (4) 35-39 (4) 40-44 (5) 40-44 (5) 40-44 (5) 45-49 (6) 45-49 (6) 45-49 (6) 50-54 (7) 50-54 (7) 50-54 (7) 55-59 (8) 55-59 (8) 55-59 (8) 60-65 (9) 60-65 (9) 60-65 (9)

Slide 17 Summary Ø Circadian variation patterns of HRV diminish by age Ø Women show lower variation patterns Ø Sex differences apparent in most HRV measures Ø but only up to age group 50-54 in this sample

Slide 18 Conflict of interest: none to declare Acknowledgement: MNJs position was funded through the Physician Scientist Program (Medical Faculty Heidelberg, Heidelberg University) from 9/15 to 3/17 Marc.Jarczok@gmail.com Find me on:

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