RR Interval Variability Is Inversely Related to Inflammatory Markers: The CARDIA Study

Bekrefter at svak vagus gir økt betennelse. Stor studie som inkluderte over 750 deltakere.


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.

To our knowledge, these are the first results demonstrating inverse relationships between inflammatory markers and indices of cardiac autonomic regulation in a large sample of healthy young adults. These findings are consistent with evidence from animal studies indicating that the cholinergic anti-inflammatory pathway counter-regulates inflammation.

It now appears that in our data from the CARDIA study of heart disease in young adults there is an inverse relationship between low frequency RR interval variability and the inflammatory markers IL-6 and CRP, even after control of relevant covariates and cardioactive medications or hypertension or diabetes, which is consistent with the hypothesis of a cholinergic anti-inflammatory pathway that regulates inflammation in humans.

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