Numerous epidemiological studies demonstrate that sudden cardiac death, pulmonary embolism, myocardial infarction, and stroke have a 24-hour daily pattern with a broad peak between 9:00 to 11:00 AM. The mechanisms underlying this daily pattern are unknown. As an important first step to elucidate mechanisms, we propose an approach that combines circadian cardiovascular physiology with analysis of a unique existing data set using novel statistical approaches that we have developed and shown to be sensitive indicators of cardiac dynamics and cardiac risk. Our primary mechanistic aim is to distinguish the separate effects upon cardiac dynamics of (i) the intrinsic circadian rhythm and of (ii) circadian variations in activity level. We will analyze existing data sets of four physiologically related variables (heart rate, blood pressure, temperature and activity level) that were simultaneously recorded in ostensibly healthy individuals throughout two complementary circadian protocols in which subjects' behaviors (including activity level and sleep-wake cycle) are controlled and the environment is constant. The protocols were: (i) a 10 day Forced Desynchrony protocol (wherein subjects' sleep-wake cycles are adjusted to 28 hours so that their behaviors occur across all circadian phases) and (ii) a 38 hour constant routine protocol (wherein subjects remain awake and semi-recumbent). Core body temperature will be used as a circadian phase marker. From these data we will extract complementary statistical indices of dynamical structure with our novel and sensitive analysis tools: (i) Cumulative Variation Amplitude Analysis; (ii) Detrended Fluctuation Analysis; (ii) Magnitude Scaling Analysis; and (iii) Multifractal Analysis. Analyses of these statistics in relation to the phase of the circadian rhythm, or separately the behavioral pattern, may reveal cardiac dynamics related to the daily pattern of cardiovascular vulnerability, and will enable us to deduce mechanistic links among variables that could underlie the cardiac dynamics. Further, by comparing indices obtained from young and older individuals under identical laboratory conditions, we aim to uncover specific age-related changes in cardiac dynamics that may underlie the age-related increase in cardiac risk. Our future aim (beyond this application) would be to determine whether the results in healthy individuals relate to patients with known cardiovascular risk. We believe that such studies may ultimately help rationalize chronobiological therapies for cardiovascular diseases in terms of modification of activity levels or timed pharmacological intervention. ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL071972-04
Application #
7162116
Study Section
Special Emphasis Panel (ZRG1-HOP-G (90))
Program Officer
Lathrop, David A
Project Start
2002-09-10
Project End
2008-11-30
Budget Start
2006-12-01
Budget End
2007-11-30
Support Year
4
Fiscal Year
2007
Total Cost
$196,021
Indirect Cost
Name
Boston University
Department
Physics
Type
Schools of Arts and Sciences
DUNS #
049435266
City
Boston
State
MA
Country
United States
Zip Code
02215
Schmitt, Daniel T; Stein, Phyllis K; Ivanov, Plamen Ch (2009) Stratification pattern of static and scale-invariant dynamic measures of heartbeat fluctuations across sleep stages in young and elderly. IEEE Trans Biomed Eng 56:1564-73
Ivanov, Plamen Ch; Ma, Qianli D Y; Bartsch, Ronny P et al. (2009) Levels of complexity in scale-invariant neural signals. Phys Rev E Stat Nonlin Soft Matter Phys 79:041920
Ivanov, Plamen Ch; Hu, Kun; Hilton, Michael F et al. (2007) Endogenous circadian rhythm in human motor activity uncoupled from circadian influences on cardiac dynamics. Proc Natl Acad Sci U S A 104:20702-7
Hu, K; Scheer, F A J L; Ivanov, P Ch et al. (2007) The suprachiasmatic nucleus functions beyond circadian rhythm generation. Neuroscience 149:508-17
Ivanov, Plamen Ch (2007) Scale-invariant aspects of cardiac dynamics. Observing sleep stages and circadian phases. IEEE Eng Med Biol Mag 26:33-7
Schmitt, Daniel T; Ivanov, Plamen Ch (2007) Fractal scale-invariant and nonlinear properties of cardiac dynamics remain stable with advanced age: a new mechanistic picture of cardiac control in healthy elderly. Am J Physiol Regul Integr Comp Physiol 293:R1923-37
de la Casa, M A; de la Rubia, F J; Ivanov, Plamen Ch (2007) Patterns of phase-dependent spiral wave attenuation in excitable media. Phys Rev E Stat Nonlin Soft Matter Phys 75:051923
de la Casa, Miguel A; de la Rubia, F Javier; Ivanov, Plamen Ch (2007) Patterns of spiral wave attenuation by low-frequency periodic planar fronts. Chaos 17:015109
Chen, Zhi; Hu, Kun; Stanley, H Eugene et al. (2006) Cross-correlation of instantaneous phase increments in pressure-flow fluctuations: applications to cerebral autoregulation. Phys Rev E Stat Nonlin Soft Matter Phys 73:031915
Xu, Limei; Chen, Zhi; Hu, Kun et al. (2006) Spurious detection of phase synchronization in coupled nonlinear oscillators. Phys Rev E Stat Nonlin Soft Matter Phys 73:065201

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