First Evaluation of an Index of Low Vagally-Mediated Heart Rate Variability as a Marker of Health Risks in Human Adults: Proof of Concept.

Multiple studies have demonstrated low vagally-mediated heart rate variability (HRV) being associated with a range of risk factors for heart disease and stroke, including inflammation, hyperglycemia, hyperlipidemia, and hypertension. Yet, no cut point exists that indicates elevated risk. In the present study we sought to identify a cut point-value for HRV that is associated with elevated risk across a range of known risk factors. METHODS:A total of 9550 working adults from 19 study sites took part in a health assessment that included measures of inflammation, hyperglycemia, hyperlipidemia, and hypertension and vagally-mediated HRV (Root mean square of successive differences between normal heartbeats (RMSSD)). Multiple age and sex adjusted logistic regressions were calculated per risk factor (normal versus clinical range), with RMSSD being entered in binary at different cut points ranging from 15-39 msec with a 2 msec increment. RESULTS:For daytime RMSSD, values below 25 ± 4 indicated elevated risk (odds ratios (OR) 1.5-3.5 across risk factors). For nighttime RMSSD, values below 29 ± 4 indicated elevated risk (OR 1.2-2.0). CONCLUSION:These results provide the first evidence that a single value of RMSSD may be associated with elevated risk across a range of established cardiovascular risk factors and may present an easy to assess novel marker of cardiovascular risk

Daily commuting to work is not associated with variables of health

Background: Commuting to work is thought to have a negative impact on employee health. We tested the association of work commute and different variables of health in German industrial employees. Methods: Self-rated variables of an industrial cohort (n = 3805; 78.9 % male) including absenteeism, presenteeism and indices reflecting stress and well-being were assessed by a questionnaire. Fasting blood samples, heart-rate variability and anthropometric data were collected. Commuting was grouped into one of four categories: 0–19.9, 20–44.9, 45–59.9, ≥60 min travelling one way to work. Bivariate associations between commuting and all variables under study were calculated. Linear regression models tested this association further, controlling for potential confounders. Results: Commuting was positively correlated with waist circumference and inversely with triglycerides. These associations did not remain statistically significant in linear regression models controlling for age, gender, marital status, and shiftwork. No other association with variables of physical, psychological, or mental health and well-being could be found. Conclusions: The results indicate that commuting to work has no significant impact on well-being and health of German industrial employees

Circadian Rhythms of the Autonomic Nervous System: Scientific Implication and Practical Implementation

Circadian rhythms are omnipresent in almost any biosignal. In this chapter, we join them with the need for practical tools for screening in preventive settings and point out heart rate variability (HRV), a measure of autonomic nervous system activity, as a chronobiologic, unspecific index of mental and physical health. We discuss methods to calculate the circadian variation of HRV measures, particularly the cosinor procedure. We present reference values for circadian variation parameters of HRV and data concerning reproducibility. Furthermore, we show data giving first evidence of HRV as a comprehensive health index by showing altered circadian variation patterns of HRV depending on mental (trait dysthymia) as well as physical (inflammatory markers) health. Finally, we present examples of disturbed chronobiology of HRV in clinical and preventive settings and its practical application in medical consultation

Improvement of pain experience and changes in heart rate variability through music-imaginative pain treatment

Music-imaginative Pain Treatment (MIPT) is a form of music therapy addressing pain experience and affective attitudes toward pain. It includes two self-composed music pieces: one dedicated to the pain experience (pain music, PM) and the other to healing imagination (healing music, HM). Our non-experimental study addresses patients with chronic somatoform pain disorders participating in MIPT. The goal is to gain insight into the direct effect mechanisms of MIPT by combining outcome measures on both the objective physiological and subjective perception levels. The research questions are directed toward changes in pain experience and heart rate variability and their correlations. Thirty-seven hospitalized patients with chronic or somatoform pain disorders receiving MIPT participated in this study. Demographic data and psychometric measures (Symptom Check List SCL90, Childhood Trauma Questionnaire CTQ) were collected to characterize the sample. Subjective pain experience was measured by McGill Pain Questionnaire (SF-MPQ), and Heart Rate Variability by 24 h-ECG. Data analysis shows a reduction of reported pain from MT1 = 19.1 (SD = 7.3) to MT2 = 10.6 (SD = 8.0) in all dimensions of the SF-MPQ. HRV analyses shows a reduced absolute power during PM and HM, while a relative shift in the autonomic system toward higher vagal activity appears during HM. Significant correlations between HRV and MPQ could not be calculated. Findings are interpreted as a physiological correlate to the psychological processes of the patients. Future studies with more participants, a control-group design, and the integration of medium- and long-term effects are recommended

Elevated HbA1c levels and the accumulation of differentiated T cells in CMV+ individuals

Aims/hypothesis Biological ageing of the immune system, or immunosenescence, predicts poor health and increased mortality. A hallmark of immunosenescence is the accumulation of differentiated cytotoxic T cells (CD27−CD45RA+/−; or dCTLs), partially driven by infection with the cytomegalovirus (CMV). Immune impairments reminiscent of immunosenescence are also observed in hyperglycaemia, and in vitro studies have illustrated mechanisms by which elevated glucose can lead to increased dCTLs. This study explored associations between glucose dysregulation and markers of immunosenescence in CMV+ and CMV− individuals. Methods A cross-sectional sample of participants from an occupational cohort study (n = 1,103, mean age 40 years, 88% male) were assessed for HbA1c and fasting glucose levels, diabetes, cardiovascular risk factors (e.g. lipids), numbers of circulating effector memory (EM; CD27−CD45RA−) and CD45RA re-expressing effector memory (EMRA; CD27−CD45RA+) T cells, and CMV infection status. Self-report and physical examination assessed anthropometric, sociodemographic and lifestyle factors. Results Among CMV+ individuals (n = 400), elevated HbA1c was associated with increased numbers of EM (B = 2.75, p \u3c 0.01) and EMRA (B = 2.90, p \u3c 0.01) T cells, which was robust to adjustment for age, sex, sociodemographic variables and lifestyle factors. Elevated EM T cells were also positively associated with total cholesterol (B = 0.04, p \u3c 0.05) after applying similar adjustments. No associations were observed in CMV− individuals. Conclusions/interpretation The present study identified consistent associations of unfavourable glucose and lipid profiles with accumulation of dCTLs in CMV+ individuals. These results provide evidence that the impact of metabolic risk factors on immunity and health can be co-determined by infectious factors, and provide a novel pathway linking metabolic risk factors with accelerated immunosenescence. Electronic supplementary material The online version of this article (doi:10.1007/s00125-015-3731-4) contains peer-reviewed but unedited supplementary material, which is available to authorised users

Rural participants raised in the presence of farm animals show less immune activation following acute psychosocial stress

Urbanization is on the rise, although the urban environment is linked to an increased prevalence of both physical and mental disorders. Human and animal studies suggest that an over-reactive immune system not only accompanies stress-associated disorders, but might even be causally involved in their pathogenesis. Here we show in young (mean age, years, (SD): rural, 25.1 (0.78); urban, 24.5 (0.88)) healthy human volunteers that urban upbringing in the absence of pets (n=20), relative to rural upbringing in the presence of farm animals (n=20), was associated with an exaggerated systemic immune activation following psychosocial stress. Questionnaires, plasma cortisol, and salivary alpha-amylase, however, indicated that the experimental protocol was more stressful and anxiogenic for rural participants. In detail, in response to the Trier Social Stress Test (TSST), participants with an urban versus rural upbringing showed a more pronounced increase in the number of peripheral blood mononuclear cells (PBMCs) and plasma interleukin (IL)-6 concentrations. Moreover, ex vivo cultured PBMCs from urban versus rural participants secreted more IL-6 in response to the T cell-specific mitogen concanavalin A (ConA). In turn, anti-inflammatory IL-10 secretion was suppressed following TSST in urban versus rural participants, suggesting immunoregulatory deficits in urban participants following social stress. Together, our findings support the hypothesis that urban upbringing in the absence of pets, in contrast to rural upbringing in the presence of farm animals, increases the vulnerability for stress-associated physical and mental disorders by compromising adequate resolution of systemic immune activation following social stress and, in turn, aggravating stress-associated systemic immune activation

Association of the Salivary Microbiome With Animal Contact During Early Life and Stress-Induced Immune Activation in Healthy Participants

The prevalence of stress-associated somatic and psychiatric disorders is increased in environments offering a narrow relative to a wide range of microbial exposure. Moreover, different animal and human studies suggest that an overreactive immune system not only accompanies stress-associated disorders, but might even be causally involved in their pathogenesis. In support of this hypothesis, we recently showed that urban upbringing in the absence of daily contact with pets, compared to rural upbringing in the presence of daily contact with farm animals, is associated with a more pronounced immune activation following acute psychosocial stressor exposure induced by the Trier Social Stress Test (TSST). Here we employed 16S rRNA gene sequencing to test whether this difference in TSST-induced immune activation between urban upbringing in the absence of daily contact with pets (n = 20) compared with rural upbringing in the presence of daily contact with farm animals (n = 20) is associated with differences in the composition of the salivary microbiome. Although we did not detect any differences in alpha or beta diversity measures of the salivary microbiome between the two experimental groups, statistical analysis revealed that the salivary microbial beta diversity was significantly higher in participants with absolutely no animal contact (n = 5, urban participants) until the age of 15 compared to all other participants (n = 35) reporting either daily contact with farm animals (n = 20, rural participants) or occasional pet contact (n = 15, urban participants). Interestingly, when comparing these urban participants with absolutely no pet contact to the remaining urban participants with occasional pet contact, the former also displayed a significantly higher immune, but not hypothalamic-pituitary-adrenal (HPA) axis or sympathetic nervous system (SNS) activation, following TSST exposure. In summary, we conclude that only urban upbringing with absolutely no animal contact had long-lasting effects on the composition of the salivary microbiome and potentiates the negative consequences of urban upbringing on stress-induced immune activation.</p

Lower values of a novel index of Vagal-Neuroimmunomodulation are associated to higher all-cause mortality in two large general population samples with 18&nbsp;year follow up.

In recent clinical practice, a biomarker of vagal neuroimmunomodulation (NIM), namely the ratio of vagally-mediated heart rate variability (vmHRV) and CRP, was proposed to index the functionality of the cholinergic anti-inflammatory pathway. This study aims to transfer and extend the previous findings to two general population-based samples to explore the hypothesis that NIM-ratio is associated with all-cause mortality. Two large population studies (MIDUS 2: N = 1255 and Whitehall II wave 5: N = 7870) with complete data from a total of N = 3860 participants (36.1% females; average age = 56.3&nbsp;years; 11.1% deaths, last exit 18.1&nbsp;years post inclusion) were available. NIM indices were calculated using the vagally-mediated HRV measure RMSSD divided by measures of CRP (NIMCRP) or IL-6 (NIMIL6). The NIM-ratios were quartiled and entered into age, ethnicity and body mass index adjusted Cox proportional hazards models. For NIMIL6 the lowest quartile was 45% more likely to die during the observed period (max. 18&nbsp;years follow-up) compared to the highest quartile (HR = 0.55 CI 0.41-0.73; p &lt; .0001). NIMCRP parallel these results. Here we show that an easily computable index of IL-6 inhibition is associated with all-cause mortality in two large general population samples. These results suggest that this index might be useful for risk stratification and warrant further examination