The relationship between heart rate variability and inflammatory markers in cardiovascular diseases

INTRODUCTION Recent evidence implicates a cholinergic anti-inflammatory pathway. Because vagus nerve activity mediates some heart rate variability (HRV), this qualitative review examines the literature concerning circulating cytokines and HRV in cardiovascular function in humans. This qualitative review examines the literature concerning circulating cytokines and HRV in cardiovascular function in humans. METHODS Thirteen studies on HRV, inflammation, and cardiovascular function were located by electronic library search and descriptively reviewed. RESULTS The relationship between HRV and inflammation was studied in healthy controls, patients with acute or stable coronary heart disease (CHD), patients with metabolic syndrome or impaired glucose tolerance and patients with kidney failure. Investigations focused mainly on Interleukin-6 (IL-6) and C-reactive peptide (CRP). The majority of reviewed studies reported that parasympathetic nervous system tone as inferred from heart rate variability is inversely related to inflammatory markers (r values between -0.2 and -0.4). The relationships with inflammatory markers were similar whether derived from ECG signals as short as 5-30min or from 24-h ECG readings for HRV analyses. While inflammatory markers appear to be related to HRV, it is a mistake to assume that the traditional "vagal measures" of HRV (such as high frequency heart rate variability) are the driving factors. Indeed, low frequency heart rate variability, a complex measure reflecting both parasympathetic and sympathetic activity, is the more commonly associated measure linked to inflammatory markers. DISCUSSION Heart rate variability is inversely correlated with inflammatory markers in healthy individuals as well as in those with cardiovascular diseases.

[1]  K. Tracey,et al.  Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin , 2000, Nature.

[2]  P. Vardas,et al.  Association of impaired glucose tolerance with increased heart rate and subclinical inflammation. , 2005, Hellenic journal of cardiology : HJC = Hellenike kardiologike epitheorese.

[3]  J. Woody,et al.  Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor α (cA2) versus placebo in rheumatoid arthritis , 1994, The Lancet.

[4]  K. Tracey,et al.  Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis , 2004, Nature Medicine.

[5]  S A Stansfeld,et al.  Adrenocortical, Autonomic, and Inflammatory Causes of the Metabolic Syndrome: Nested Case-Control Study , 2002, Circulation.

[6]  S. Targan,et al.  A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group. , 1997, The New England journal of medicine.

[7]  N. Frasure-smith,et al.  Depression and coronary artery disease. , 2006, Herz.

[8]  Michele A. Parker,et al.  Relationship of Heart Rate Variability to Parasympathetic Effect , 2001, Circulation.

[9]  D. Rempel,et al.  Influence of time pressure and verbal provocation on physiological and psychological reactions during work with a computer mouse , 2002, European Journal of Applied Physiology.

[10]  M. Turiel,et al.  Power Spectral Analysis of Heart Rate and Arterial Pressure Variabilities as a Marker of Sympatho‐Vagal Interaction in Man and Conscious Dog , 1986, Circulation research.

[11]  D. Nance,et al.  Autonomic innervation and regulation of the immune system (1987–2007) , 2007, Brain, Behavior, and Immunity.

[12]  I. Penttilä,et al.  C-reactive protein, fibrinogen, interleukin-6 and tumour necrosis factor-α in the prognostic classification of unstable angina pectoris , 2001 .

[13]  K. Tracey,et al.  Cholinergic stimulation blocks endothelial cell activation and leukocyte recruitment during inflammation , 2005, The Journal of experimental medicine.

[14]  A. Steptoe,et al.  Natural killer cell and proinflammatory cytokine responses to mental stress: associations with heart rate and heart rate variability , 2003, Biological Psychology.

[15]  A. Garde,et al.  Effects of mental and physical demands on heart rate variability during computer work , 2002, European Journal of Applied Physiology.

[16]  A. Malliani,et al.  Heart rate variability. Standards of measurement, physiological interpretation, and clinical use , 1996 .

[17]  I. Janszky,et al.  Inflammatory markers and heart rate variability in women with coronary heart disease , 2004, Journal of internal medicine.

[18]  Ralph J. Verdino,et al.  Changes in heart rate and heart rate variability before ambulatory ischemic events , 2001 .

[19]  G. Liakos,et al.  Relations of inflammatory markers to lipid levels and autonomic tone in patients with moderate and severe chronic kidney disease and in patients under maintenance hemodialysis. , 2005, Clinical nephrology.

[20]  E. Toft,et al.  C‐Reactive Protein Is Associated with Heart Rate Variability , 2007, Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc.

[21]  Motoyuki Nakamura,et al.  Association of decreased variation of R-R interval and elevated serum C-reactive protein level in a general population in Japan. , 2006, International heart journal.

[22]  M. Halinen,et al.  C-reactive protein, fibrinogen, interleukin-6 and tumour necrosis factor-alpha in the prognostic classification of unstable angina pectoris. , 2001, Annals of medicine.

[23]  S. Targan,et al.  A Short-Term Study of Chimeric Monoclonal Antibody cA2 to Tumor Necrosis Factor α for Crohn's Disease , 1997 .

[24]  A. Peters,et al.  Relationship between electrocardiographic and biochemical variables in coronary artery disease. , 2007, International journal of cardiology.

[25]  H. Hein,et al.  Increased heart rate and reduced heart-rate variability are associated with subclinical inflammation in middle-aged and elderly subjects with no apparent heart disease. , 2004, European heart journal.

[26]  G. Lip,et al.  Markers of inflammation in acute coronary syndromes: Association with increased heart rate and reductions in heart rate variability , 2005, Clinical cardiology.

[27]  G. Breithardt,et al.  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. , 1996 .

[28]  P. Stein,et al.  Heart Rate Variability: Measurement and Clinical Utility , 2005, Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc.

[29]  Splenectomy inactivates the cholinergic antiinflammatory pathway during lethal endotoxemia and polymicrobial sepsis , 2006 .

[30]  J. Fleiss,et al.  Frequency Domain Measures of Heart Period Variability and Mortality After Myocardial Infarction , 1992, Circulation.

[31]  G. Liakos,et al.  Inverse relation of C-reactive protein levels to heart rate variability in patients after acute myocardial infarction. , 2007, Hellenic journal of cardiology : HJC = Hellenike kardiologike epitheorese.

[32]  T. van der Poll,et al.  The vagus nerve and nicotinic receptors modulate experimental pancreatitis severity in mice. , 2006, Gastroenterology.

[33]  A. K. Blangsted,et al.  The effect of mental stress on heart rate variability and blood pressure during computer work , 2004, European Journal of Applied Physiology.

[34]  A. Bitto,et al.  Activation of an efferent cholinergic pathway produces strong protection against myocardial ischemia/reperfusion injury in rats* , 2005, Critical care medicine.

[35]  Kevin J. Tracey,et al.  The inflammatory reflex , 2002, Nature.

[36]  R. Känel,et al.  Myocardial infarction and post-traumatic stress disorder: frequency, outcome, and atherosclerotic mechanisms , 2006, European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology.

[37]  Y. Yamamoto,et al.  Effects of Stroop color-word conflict test on the autonomic nervous system responses. , 1997, The American journal of physiology.

[38]  A. Rebuzzi,et al.  Relation of heart rate variability to serum levels of C-reactive protein in patients with unstable angina pectoris. , 2006, The American journal of cardiology.

[39]  P. Ridker,et al.  Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. , 2000, Circulation.

[40]  J. V. van Engelshoven,et al.  Is there more than C-reactive protein and fibrinogen? The prognostic value of soluble CD40 ligand, interleukin-6 and oxidized low-density lipoprotein with respect to coronary and cerebral vascular disease. , 2006, Atherosclerosis.

[41]  T. Seeman,et al.  RR Interval Variability Is Inversely Related to Inflammatory Markers: The CARDIA Study , 2007, Molecular medicine.

[42]  A. Goldberger.  Non-linear dynamics for clinicians: chaos theory, fractals, and complexity at the bedside , 1996, The Lancet.

[43]  J. Saul,et al.  Beat-to-Beat Variations of Heart Rate Reflect Modulation of Cardiac Autonomic Outflow , 1990 .

[44]  R. Nolan,et al.  C-reactive protein modulates vagal heart rate control in patients with coronary artery disease. , 2007, Clinical science.

[45]  J. Jukema,et al.  Chemokines and atherosclerotic plaque progression: towards therapeutic targeting? , 2007, Current pharmaceutical design.

[46]  H. Huikuri,et al.  Fractal analysis of heart rate variability and mortality after an acute myocardial infarction. , 2002, The American journal of cardiology.