RR Interval Variability Is Inversely Related to Inflammatory Markers: The CARDIA Study
Open accessAbstract
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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Decreased parasympathetic nervous system activity has been associated with increased inflammation.
“decreased parasympathetic37”
From Association of depressive disorders, depression characteristics and antidepressant medication with inflammation (2012) · cites this paper as [37]
Chronic inflammation such as in rheumatoid arthritis is accompanied by vagal hypoactivity and sympathetic hyperactivity.
“However, chronic inflammation such as in RA is accompanied by vagal hypoactivity and sympathetic hyperactivity [108-110].”
From Interaction of the endocrine system with inflammation: a function of energy and volume regulation (2014) · cites this paper as [108]
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- Authors
- Sloan, R. P., McCreath, H., Tracey, K. J., Sidney, S., Liu, K., & Seeman, T.
- Affiliations
- Columbia University Irving Medical Center (US)
- University of California, Los Angeles (US)
- Northwell Health (US)
- Kaiser Permanente (US)
- Northwestern University (US)
- Corresponding author
- Sloan, Richard P.
- Venue
- Molecular Medicine
- Published
- 2007-03
- Volume
- 13
- Issue
- 3-4
- Pages
- 178-184
- ISSN
- 1076-1551 (ISSN-L)
- 1528-3658
- PMC
- PMC1892756
- OpenAlex
- W109337650
- Cited by
- 264
- References
- 25
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 6 · 2023: 6 · 2022: 12 · 2021: 8 · 2020: 13 · 2019: 16 · 2018: 18 · 2017: 19 · 2016: 17 · 2015: 13 · 2014: 21 · 2013: 21 · 2012: 18
- FWCI
- 12.17
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Molecular Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Health and Mental Health
- Keywords
- RR interval variability, heart rate variability, cardiac vagal modulation, cholinergic anti-inflammatory pathway, vagus nerve, inflammatory markers, C-reactive protein, interleukin-6, cytokines, atherosclerosis, young adults, CARDIA study
- MeSH terms
- Adolescent, Adult, Black or African American, Blood Pressure, C-Reactive Protein, Coronary Artery Disease, Cross-Sectional Studies, Electrocardiography, Female, Heart, Heart Rate, Humans, Inflammation, Longitudinal Studies, Male, Risk Factors, United States, Vagus Nerve, Cohort Studies, Multicenter Studies as Topic, Biomarkers, Interleukin-6, Body Mass Index, Multivariate Analysis, White People
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