Abstract

Background
Stress and autonomic nervous system dysfunction have a huge impact on contemporary human life with respect to quality of life, workability, and a broad range of diseases including the risk of premature death. For national health care budgets, the costs are a major challenge. Presently, no distinct diagnostic method exists with respect to stress, and especially with respect to distinguishing between transient and persistent stress. Furthermore, autonomic nervous system dysfunction is presently evaluated using a range of peripheral autonomic measurements, and a clear diagnostic measurement from the brain is thus missing. For intervention of autonomic dysfunction, no evidence-based intervention is presently available.

Methods
Based on clinical observations and a series of pilot studies, we tested the following hypotheses:

1) The Pressure Pain Sensitivity measurement of the chest bone (PPS) measures stress and can distinguish between transient and persistent stress, as the latter is associated with autonomic nervous system dysfunction, measured as an elevated PPS at rest.

2) PPS measures the function of the autonomic nervous system in the brain, and an elevated resting PPS reflects autonomic dysfunction, mainly as sympathetic autonomic hyperactivity, and is most probably controlled by a non-beta-adrenergic receptor system.

3) Reduction of an elevated PPS is associated with a reduction of persistent stress and autonomic dysfunction.

4) A specific non-pharmacological intervention can reduce an elevated resting PPS. This intervention is home-based and focuses on daily PPS measurements as a feedback measurement for behavioral guidance, daily non-noxious sensory nerve stimulation for PPS reduction, and ongoing professional surveillance for proactive action if PPS measurements are missing or deviating.

The hypotheses are currently tested in a combination of prospective experimental, cross-sectional, and randomized controlled interventional trials with top performers, healthy working people, people with type 2 diabetes, and people with stable ischemic heart disease.

Results
In healthy office workers, heart disease patients, and type 2 diabetes patients, it was found that PPS was associated with a broad range of questionnaire-related measurements of stress as well as with a broad range of cardiovascular health risk factors controlled by the autonomic nervous system (e.g., depression, blood pressure, pulse rate, and serum cholesterol). In these populations, the used intervention was found to reduce an elevated PPS, which was associated with improvement of the mentioned health risk factors. Beta-blockade medication had no effect on PPS, but inhibited the effect of reducing PPS on depression, work of the heart, blood pressure, and heart rate variability. In heart disease patients a meta-analysis showed a mortality rate substantially significant and 57% lower than that of the general population. In type 2 diabetes patients the reduction of dysregulated glycated hemoglobin was reduced by 22%. These effects were obtained with no risk of side effects or complications.

Conclusions
At present, the accumulated scientific data find the PPS measurement to be an indicator for physiological stress, brain resilience, and autonomic dysfunction.

The associated intervention, the Ballegaard Stress Care Program®, reduces stress and autonomic dysfunction in general.

The findings with respect to beta-blockade medication suggest that PPS mainly measures sympathetic autonomic activity and is controlled in areas of the brain with no beta-adrenergic receptors, most probably by the orexin receptor system of the lateral hypothalamus.

The scientific data allow for a fully evidence-based public implementation of the PPS measurement and the associated PPS home-based biofeedback guided intervention.