Endogenous circadian rhythm in an index of cardiac vulnerability independent of changes in behavior
Open accessAbstract
There exists a robust day/night pattern in the incidence of adverse cardiac events with a peak at ≈10 a.m. This peak traditionally has been attributed to day/night patterns in behaviors affecting cardiac function in vulnerable individuals. However, influences from the endogenous circadian pacemaker independent from behaviors may also affect cardiac control. Heartbeat dynamics under healthy conditions exhibit robust complex fluctuations characterized by self-similar temporal structures, which break down under pathologic conditions. We hypothesize that these dynamical features of the healthy human heartbeat have an endogenous circadian rhythm that brings the features closer to those observed under pathologic conditions at the endogenous circadian phase corresponding to ≈10 a.m. We investigate heartbeat dynamics in healthy subjects recorded throughout a 10-day protocol wherein the sleep/wake and behavior cycles are desynchronized from the endogenous circadian cycle, enabling assessment of circadian factors while controlling for behavior-related factors. We demonstrate that the scaling exponent characterizing temporal correlations in heartbeat dynamics does exhibit a significant circadian rhythm (with a sharp peak at the circadian phase corresponding to ≈10 a.m.), which is independent from scheduled behaviors and mean heart rate. Cardiac dynamics under pathologic conditions such as congestive heart failure also are associated with a larger value of the scaling exponent of the interbeat interval. Thus, the sharp peak in the scaling exponent at the circadian phase coinciding with the period of highest cardiac vulnerability observed in epidemiological studies suggests that endogenous circadian-mediated influences on cardiac control may be involved in the day/night pattern of adverse cardiac events in vulnerable individuals.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Sympathetic tone (circulating epinephrine and norepinephrine) has large endogenous circadian rhythms (peak-to-trough amplitudes of 70% and 34% of the mean, respectively) that peak at a circadian phase equivalent to midday.
“Sympathetic tone (circulating epinephrine and norepinephrine) had large endogenous circadian rhythms (peakto-trough amplitudes of 70% and 34% of the mean, respectively) that peaked at a circadian phase equivalent to midday.”
From Role of the circadian system in cardiovascular disease (2018) · cites this paper as [107]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Heart Rate Variability: Standards of Measurement, Physiological Interpretation, and Clinical Use
Electrophysiology, T. F. O. T. E. S. O. C. T. N. A. (1996) · Circulation · doi:10.1161/01.cir.93.5.1043 · Cited by 17,159 · see citing works
Principles and Practice of Sleep Medicine
Kryger, M. H., Roth, T. G., & Dement, W. C. (2011) · Elsevier eBooks · doi:10.1016/c2009-0-59875-3 · Cited by 5,118 · see citing works
Mosaic organization of DNA nucleotides
Peng, C., Buldyrev, S. V., Havlin, S., Simons, M., Stanley, E., & Goldberger, A. L. (1994) · Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics · doi:10.1103/physreve.49.1685 · Cited by 5,002 · see citing works
Quantification of scaling exponents and crossover phenomena in nonstationary heartbeat time series
Peng, C., Havlin, S., Stanley, E., & Goldberger, A. L. (1995) · Chaos An Interdisciplinary Journal of Nonlinear Science · doi:10.1063/1.166141 · Cited by 3,865 · see citing works
Circadian Variation in the Frequency of Onset of Acute Myocardial Infarction
Muller, J. E., Stone, P. H., Turi, Z. G., Rutherford, J. D., Czeisler, C. A., Parker, C., Poole, W. K., Passamani, E., Roberts, R., Robertson, T., et al. (1985) · New England Journal of Medicine · doi:10.1056/nejm198511213132103 · Cited by 1,884 · see citing works
Stability, precision, and near-24-hour period of the human circadian pacemaker
Czeisler, C. A., Duffy, J. F., Shanahan, T. L., Brown, E. N., Mitchell, J. F., Rimmer, D. W., Ronda, J. M., Silva, E. J., Allan, J. S., Emens, J. S., et al. (1999) · Science · doi:10.1126/science.284.5423.2177 · Cited by 1,705 · see citing works
Methods for cosinor-rhythmometry.
Nelson, W. E., Tong, Y. L., Lee, J. K., & Franz Halberg, A. (1979) · PubMed · Cited by 1,701 · see citing works
Multifractality in human heartbeat dynamics
Ivanov, P. C., Amaral, L. A. N., Goldberger, A. L., Havlin, S., Rosenblum, M., Struzik, Z. R., & Stanley, H. E. (1999) · Nature · doi:10.1038/20924 · Cited by 1,666 · see citing works
Self-citationMultifractality in Human Heartbeat Dynamics.
Ivanov, P. C., Amaral, L. A. N., Goldberger, A. L., Havlin, S., Rosenblum, M. G., Struzik, Z. R., & Stanley, E. (1999) · Centrum Wiskunde & Informatica (CWI), the national research institute for mathematics and computer science in the Netherlands · Cited by 1,327 · see citing works
Self-citationEffect of trends on detrended fluctuation analysis
Hu, K., Ivanov, P. C., Chen, Z., Carpena, P., & Stanley, E. (2001) · Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics · doi:10.1103/physreve.64.011114 · Cited by 1,285 · see citing works
Self-citationCircadian variation in the frequency of sudden cardiac death.
Muller, J. E., Ludmer, P. L., Willich, S. N., Tofler, G. H., Aylmer, G., Klangos, I., & Stone, P. H. (1987) · Circulation · doi:10.1161/01.cir.75.1.131 · Cited by 1,083 · see citing works
Effect of nonstationarities on detrended fluctuation analysis
Chen, Z., Ivanov, P. C., Hu, K., & Stanley, E. (2002) · Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics · doi:10.1103/physreve.65.041107 · Cited by 957 · see citing works
Self-citationNon-linear dynamics for clinicians: chaos theory, fractals, and complexity at the bedside
Goldberger, A. L. (1996) · The Lancet · doi:10.1016/s0140-6736(96)90948-4 · Cited by 859 · see citing works
1/f Fluctuation of Heartbeat Period
Kobayashi, M., & Musha, T. (1982) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.1982.324972 · Cited by 695 · see citing works
Huikuri, H. V., Mäkikallio, T. H., Peng, C., Goldberger, A. L., Hintze, U., & Møller, M. (2000) · Circulation · doi:10.1161/01.cir.101.1.47 · Cited by 668 · see citing works
Willich, S. N., Levy, D., Rocco, M. B., Tofler, G. H., Stone, P. H., & Muller, J. E. (1987) · The American Journal of Cardiology · doi:10.1016/0002-9149(87)91027-7 · Cited by 653 · see citing works
Ck, F. (1970) · PubMed · Cited by 639 · see citing works
Dijk, D.-J., & Czeisler, C. A. (1994) · Neuroscience Letters · doi:10.1016/0304-3940(94)90841-9 · Cited by 628 · see citing works
Correlated and Uncorrelated Regions in Heart-Rate Fluctuations during Sleep
Armin Bunde, A., Havlin, S., Kantelhardt, J. W., Penzel, T., Peter, J.-H., & Voigt, K. (2000) · Physical Review Letters · doi:10.1103/physrevlett.85.3736 · Cited by 545 · see citing works
Morning increase in onset of ischemic stroke.
Marler, J. R., Price, T. R., Clark, G., Muller, J. E., Robertson, T., Mohr, J. P., Hier, D. B., Wolf, P. A., Caplan, L. R., & Foulkes, M. A. (1989) · Stroke · doi:10.1161/01.str.20.4.473 · Cited by 515 · see citing works
Scaling behaviour of heartbeat intervals obtained by wavelet-based time-series analysis
Ivanov, P. C., Rosenblum, M. G., Peng, C., Mietus, J. E., Havlin, S., Stanley, E., & Goldberger, A. L. (1996) · Nature · doi:10.1038/383323a0 · Cited by 513 · see citing works
Self-citationPenzel, T., Kantelhardt, J. W., Grote, L., Peter, J. H., & Armin Bunde, A. (2003) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.2003.817636 · Cited by 493 · see citing works
Ho, K. K. L., Moody, G. B., Peng, C.-K., Mietus, J. E., Larson, M. G., Levy, D., & Goldberger, A. L. (1997) · Circulation · doi:10.1161/01.cir.96.3.842 · Cited by 489 · see citing works
Buijs, R. M., la Fleur, S. E., Wortel, J., van Heyningen, C., Zuiddam, L., Mettenleiter, T. C., Kalsbeek, A., Nagai, K., & Niijima, A. (2003) · The Journal of Comparative Neurology · doi:10.1002/cne.10765 · Cited by 356 · see citing works
Analysis of possible triggers of acute myocardial infarction (the MILIS study)
Tofler, G. H., Stone, P. H., Maclure, M., Edelman, E., Davis, V. G., Robertson, T., Antman, E. M., & Muller, J. E. (1990) · The American Journal of Cardiology · doi:10.1016/0002-9149(90)90729-k · Cited by 356 · see citing works
Ridker, P. M., Manson, J. E., Buring, J. E., Muller, J. E., & Hennekens, C. H. (1990) · Circulation · doi:10.1161/01.cir.82.3.897 · Cited by 285 · see citing works
Increased onset of sudden cardiac death in the first three hours after awakening
Willich, S. N., Goldberg, R. J., Maclure, M., Perriello, L. M., & Muller, J. E. (1992) · The American Journal of Cardiology · doi:10.1016/0002-9149(92)91391-g · Cited by 284 · see citing works
Behavioral-Independent Features of Complex Heartbeat Dynamics
Amaral, L. A. N., Ivanov, P. C., Aoyagi, N., Hidaka, I., Tomono, S., Goldberger, A. L., Stanley, E., & Yamamoto, Y. (2001) · Physical Review Letters · doi:10.1103/physrevlett.86.6026 · Cited by 259 · see citing works
Self-citationEffect of nonlinear filters on detrended fluctuation analysis
Chen, Z., Hu, K., Carpena, P., Bernaola‐Galván, P., Stanley, E., & Ivanov, P. C. (2005) · Physical Review E · doi:10.1103/physreve.71.011104 · Cited by 243 · see citing works
Self-citationStochastic feedback and the regulation of biological rhythms
Ivanov, P. C., Amaral, L. A. N., Goldberger, A. L., & Stanley, E. (1998) · Europhysics Letters (EPL) · doi:10.1209/epl/i1998-00366-3 · Cited by 241 · see citing works
Self-citationIvanov, P. C., Armin Bunde, A., Amaral, L. A. N., Havlin, S., Fritsch-Yelle, J. M., Baevsky, R. M., Stanley, E., & Goldberger, A. L. (1999) · Europhysics Letters (EPL) · doi:10.1209/epl/i1999-00525-0 · Cited by 241 · see citing works
Self-citationCircadian variation in cardiovascular events
Muller, J. E. (1999) · American Journal of Hypertension · doi:10.1016/s0895-7061(98)00278-7 · Cited by 210 · see citing works
Characterization of sleep stages by correlations in the magnitude and sign of heartbeat increments
Kantelhardt, J. W., Ashkenazy, Y., Ivanov, P. C., et al. (2002) · Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics · doi:10.1103/physreve.65.051908 · Cited by 186 · see citing works
Self-citationTime of onset of symptoms of acute myocardial infarction
Goldberg, R. J., Brady, P. M., Muller, J. E., Chen, Z., de Groot, M., Zonneveld, P., & Dalen, J. E. (1990) · The American Journal of Cardiology · doi:10.1016/0002-9149(90)90577-n · Cited by 183 · see citing works
Self-citationTofler, G. H., Muller, J. E., Stone, P. H., Forman, S. A., Solomon, R. E., Knatterud, G. L., & D, E. B. M. (1992) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(92)90356-r · Cited by 180 · see citing works
Fractal landscapes and molecular evolution: modeling the myosin heavy chain gene family
Buldyrev, S. V., Goldberger, A. L., Havlin, S., Peng, C., Stanley, E., Stanley, M. H. R., & Simons, M. (1993) · Biophysical Journal · doi:10.1016/s0006-3495(93)81290-6 · Cited by 144 · see citing works
Tofler, G. H., Gebara, O., Mittleman, M. A., Taylor, P. G., Siegel, W., Venditti, F. J., Rasmussen, C. A. F., Muller, J. E., & for the CPI Investigators (1995) · Circulation · doi:10.1161/01.cir.92.5.1203 · Cited by 128 · see citing works
Correlation differences in heartbeat fluctuations during rest and exercise
Karasik, R., Sapir, N., Ashkenazy, Y., et al. (2002) · Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics · doi:10.1103/physreve.66.062902 · Cited by 127 · see citing works
Cannon, C. P., McCabe, C. H., Stone, P. H., Schactman, M., Thompson, B., Theroux, P., Gibson, R. S., Feldman, T., Kleiman, N. S., Tofler, G. H., et al. (1997) · The American Journal of Cardiology · doi:10.1016/s0002-9149(97)00743-1 · Cited by 122 · see citing works
Willich, S. N., Pohjola‐Sintonen, S., Bhatia, S. J. S., Shook, T., Tofler, G. H., Muller, J. E., Curtis, D. G., Williams, G. H., & Stone, P. H. (1989) · Circulation · doi:10.1161/01.cir.79.3.557 · Cited by 105 · see citing works
Endogenous circadian control of the human autonomic nervous system
Hilton, M. F., Umali, M., Czeisler, C. A., Wyatt, J. K., & Shea, S. A. (2002) · Computers in cardiology · doi:10.1109/cic.2000.898490 · Cited by 51 · see citing works
Self-citationAronson, D. (2001) · Chronobiology International · doi:10.1081/cbi-100001175 · Cited by 39 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- [15]Kobayashi, M. & Musha, T. (1982) IEEE Trans. Biomed. Eng. 29, 456-457.
- [39]Penzel, T., Kantelhardt, J. W., Grote, L., Peter, J. H. & Bunde, A. (2003) IEEE Trans. Biomed. Eng. 50, 1143-1451.
- [41]Chen, Z., Hu, K., Carpena, P., Bernaola-Galvan P., Stanley, H. E. & Ivanov, P. Ch., Phys. Rev. E Nonlin. Soft Matter Phys. 71, in press.
Cited by
Sorted by citations
Adverse metabolic and cardiovascular consequences of circadian misalignment
Scheer, F. A. J. L., Hilton, M. F., Mantzoros, C. S., & Shea, S. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808180106 · Cited by 2,351 · see citing works
Self-citationRole of the circadian system in cardiovascular disease
Thosar, S. S., Butler, M. P., & Shea, S. A. (2018) · Journal of Clinical Investigation · doi:10.1172/jci80590 · Cited by 443 · see citing works
Self-citationThe Cardiomyocyte Circadian Clock: Emerging Roles in Health and Disease
Durgan, D. J., & Young, M. E. (2010) · Circulation Research · doi:10.1161/circresaha.109.209957 · Cited by 277 · see citing works
Circadian Variation of Heart Rate Variability Across Sleep Stages
Boudreau, P., Yeh, W.-H., Dumont, G. A., & Boivin, D. B. (2013) · Sleep · doi:10.5665/sleep.3230 · Cited by 235 · see citing works
Effects of circadian disruption on the cardiometabolic system
Rüger, M., & Scheer, F. A. J. L. (2009) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-009-9122-8 · Cited by 232 · see citing works
The impact of the circadian timing system on cardiovascular and metabolic function
Morris, C. J., Yang, J. N., & Scheer, F. A. J. L. (2012) · Progress in Brain Research · doi:10.1016/b978-0-444-59427-3.00019-8 · Cited by 215 · see citing works
Martino, T. A., Tata, N., Belsham, D. D., Chalmers, J., Straume, M., Lee, P., Pribiag, H., Khaper, N., Liu, P. P., Dawood, F., et al. (2007) · Hypertension · doi:10.1161/hypertensionaha.106.083568 · Cited by 196 · see citing works
Clinical aspects of human circadian rhythms
Klerman, E. B. (2005) · Journal of Biological Rhythms · doi:10.1177/0748730405278353 · Cited by 139 · see citing works
Alibhai, F. J., Tsimakouridze, E. V., Chinnappareddy, N., Wright, D. C., Billia, F., O’Sullivan, M. L., Pyle, W. G., Sole, M. J., & Martino, T. A. (2014) · Circulation Research · doi:10.1161/circresaha.114.302995 · Cited by 122 · see citing works
- Authors
- Hu, K., Ivanov, P. C., Hilton, M. F., Chen, Z., Ayers, R. T., Stanley, H. E., & Shea, S. A.
- Affiliations
- Boston University (US)
- Center for Polymer Studies and Department of Physics, Boston University, Boston, MA 02215; and Harvard Medical School and Division of Sleep Medicine, Brigham and Women's Hospital, Boston, MA 02115
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2004-12-20
- Volume
- 101
- Issue
- 52
- Pages
- 18223-18227
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC539796
- OpenAlex
- W2128811196
- Cited by
- 141
- References
- 42
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 6 · 2023: 2 · 2022: 7 · 2021: 10 · 2020: 8 · 2019: 9 · 2018: 5 · 2017: 6 · 2016: 4 · 2015: 10 · 2014: 8 · 2013: 7 · 2012: 10
- FWCI
- 3.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- Brigham and Women's Hospital (M01 RR02635)
- Deutsches Krebsforschungszentrum
- National Institutes of Health (NCRR-GCRC-M01-RR02635, RR‐02635)
- National Heart, Lung, and Blood Institute (HL76446, HL064815, K24HL076446, HL 071972, HL076409, R01HL076409, R01HL064815, R01HL071972)
- National Center for Research Resources (P41RR013622, M01RR002635)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- endogenous circadian rhythm, cardiac vulnerability, heartbeat dynamics, RR interval, scaling exponents, fractal dynamics, circadian desynchrony, sleep-wake cycle, congestive heart failure, circadian phase, cardiac regulation
- MeSH terms
- Adult, Behavior, Biological Clocks, Circadian Rhythm, Female, Heart, Heart Rate, Humans, Male, Myocardial Contraction, Myocardium, Time Factors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
