RR variability is inversely related to inflammatory markers: The CARDIA Study

Behavioral Medicine Program, Department of Psychiatry, Columbia University Medical Center, New York, NY 10032, USA.
Molecular Medicine (Impact Factor: 4.51). 03/2007; 13(3-4):178-84. DOI: 10.2119/2006–00112.Sloan
Source: PubMed


Recent evidence reveals that the immune system is under the direct control of the vagus nerve via the "cholinergic anti-inflammatory pathway." Stimulation of vagus nerve activity significantly inhibits cytokine levels in animal models, and cholinergic agents inhibit cytokine release by human macrophages. Moreover, when vagus nerve activity is decreased or absent, cytokines are overproduced. Atherosclerosis is an inflammatory disease characterized by elevated levels of CRP and IL-6, but the relationship between cardiac vagal activity and cytokine levels in healthy humans is not well understood. Here we measured RR interval variability, an index of cardiac vagal modulation, and CRP and IL-6 in 757 subjects participating in a subset of the year 15 data collection in the CARDIA study of the evolution of risk factors in young adults. Univariate analysis revealed that all indices of RRV were strongly and inversely related to IL-6 (log pg/mL b=-0.08 and -0.17 for HF and LF power, P<0.001 respectively) and CRP (log mg/L b=-0.14 and -0.26 for HF and LF power, P<0.001 respectively) levels. In the multivariate model including gender, race, age, smoking, physical activity, SBP, BMI, and disease, the inverse relationship between RRV and inflammatory markers, although slightly attenuated, remained significant. These findings are consistent with the hypothesis that diminished descending vagal anti-inflammatory signals can allow cytokine overproduction in humans.

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    • "In a multivariate model including gender, race, age, smoking, physical activity, systolic blood pressure, body mass index, and disease , there was a significant inverse relationship between heart rate variability and inflammatory markers. These findings are consistent with the hypothesis that efferent vagus activity is inversely associated with cytokine and inflammation in humans [105]. "
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    ABSTRACT: The vagus nerve modulates inflammatory responses in various organ systems. Emerging evidence indicates that the vagus can have profound and complex effects on cardiovascular function, remodeling, arrhythmias, and mortality by several mechanisms. In heart failure and during ischemia, an adverse inflammatory response can occur. The vagus nerve may modulate cardiovascular disease and outcomes by affecting inflammatory responses. Here, evidence for and components of the vagus inflammatory reflex are reviewed and evidence for and implications of effects of vagus activation on inflammation in the cardiovascular system are considered. Copyright © 2015 Elsevier Inc. All rights reserved.
    Trends in Cardiovascular Medicine 04/2015; 19. DOI:10.1016/j.tcm.2015.03.016 · 2.91 Impact Factor
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    • "The major part of this variability is constituted by alterations in respiratory mediated influence on the parasympathetic load. Further, a link between inflammatory mediators and autonomic cardiac control has been shown (Czura and Traycey, 2005; Sloan et al., 2007; Luttman- Gibson et al., 2010) and an association between low grade inflammation and cardiovascular disease has been reported (Ridker and Morrow, 2003; Celik et al., 2011). In this work, a methodology has been developed with the purpose of exploring the effects on heart rate variability in healthy humans exposed to indoor generated candle particles and particles from terpeneeozone reactions. "
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    ABSTRACT: Background Airborne particles are associated with increased morbidity and mortality due to respiratory and cardiovascular diseases in polluted areas. There is a growing interest in nano-sized particles with diameter <100 nm and their potential health effects. Heart rate variability (HRV) is a noninvasive method for cardiovascular risk prediction in high prevalent groups. Aim of study The aim was to evaluate the impact of nano-sized indoor air particles on HRV for healthy and adult females. Methods All exposures were performed as controlled chamber experiments with particle exposure from burning candles, terpene + ozone reactions or filtered air in a double-blind cross over design. Twenty-two healthy females were investigated during 10 min periods at different exposures and the reactivity in high frequency (HF) spectral band of HRV were computed. Results Heart rate was unchanged from baseline values in all groups during all experimental settings. HF power of HRV tended to increase during exposure to particles from burning candle while particles from terpene + ozone reactions tended to decrease HF power. Conclusions Exposure to nano-sized particles of burning candles or terpene + ozone reactions results in different patterns of heart rate variability, with signs of altered autonomic cardiovascular control. Practical implications This study indicates that the HRV method may be used for information on physiological responses of exposure to different nano-sized particles and contribute to the understanding of mechanisms behind health effects of particle exposures.
    Atmospheric Environment 05/2014; 88:165–171. DOI:10.1016/j.atmosenv.2014.02.003 · 3.28 Impact Factor
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    • "This can be a favorable ‘cholinergic reflex’ that might inhibit inflammation in CIDs as recently noticed [107]. However, chronic inflammation such as in RA is accompanied by vagal hypoactivity and sympathetic hyperactivity [108-110]. Thus, an anti-inflammatory and energy-storing function of the vagus nerve is probably not available. Both aspects would support ongoing inflammation in CIDs. "
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    ABSTRACT: During acute systemic infectious disease, precisely regulated release of energy-rich substrates (glucose, free fatty acids, and amino acids) and auxiliary elements such as calcium/phosphorus from storage sites (fat tissue, muscle, liver, and bone) are highly important because these factors are needed by an energy-consuming immune system in a situation with little or no food/water intake (sickness behavior). This positively selected program for short-lived infectious diseases is similarly applied during chronic inflammatory diseases. This review presents the interaction of hormones and inflammation by focusing on energy storage/expenditure and volume regulation. Energy storage hormones are represented by insulin (glucose/lipid storage and growth-related processes), insulin-like growth factor-1 (IGF-1) (muscle and bone growth), androgens (muscle and bone growth), vitamin D (bone growth), and osteocalcin (bone growth, support of insulin, and testosterone). Energy expenditure hormones are represented by cortisol (breakdown of liver glycogen/adipose tissue triglycerides/muscle protein, and gluconeogenesis; water retention), noradrenaline/adrenaline (breakdown of liver glycogen/adipose tissue triglycerides, and gluconeogenesis; water retention), growth hormone (glucogenic, lipolytic; has also growth-related aspects; water retention), thyroid gland hormones (increase metabolic effects of adrenaline/noradrenaline), and angiotensin II (induce insulin resistance and retain water). In chronic inflammatory diseases, a preponderance of energy expenditure pathways is switched on, leading to typical hormonal changes such as insulin/IGF-1 resistance, hypoandrogenemia, hypovitaminosis D, mild hypercortisolemia, and increased activity of the sympathetic nervous system and the renin-angiotensin-aldosterone system. Though necessary during acute inflammation in the context of systemic infection or trauma, these long-standing changes contribute to increased mortality in chronic inflammatory diseases.
    Arthritis research & therapy 02/2014; 16(1):203. DOI:10.1186/ar4484 · 3.75 Impact Factor
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