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How Might Sleep Apnea Lead to Serious Health Concerns like Cardiac and Cancer?

Author: Larry H Bernstein, MD, FCAP

3.3.16

3.3.16   How Might Sleep Apnea Lead to Serious Health Concerns like Cardiac and Cancer?, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 2: CRISPR for Gene Editing and DNA Repair

UPDATED on 7/23/2019

Israel-led research team develops AI-based model to detect sleep apnea | The Times of Israel

https://www.timesofisrael.com/israel-led-research-team-develops-ai-based-model-to-detect-sleep-apnea/?utm_source=dlvr.it

What is the link between sleep apnea and cardiovascular disease and is the treatment of obstructive sleep apnea (OSA) by continuous positive airway pressure in patients (CPAP) with heart failure to improve left ventricular systolic function sufficient?  There are statistics incicating the benefit of CPAP and improvement of LVSF in those patients on CPAP with CHF.  But that observation does not get at why the patients benefit, or whether the OSA is sufficient.  Don’t expect a randomized clinical trial of any design to be brought to bear on the subject, considering the ethical issues involved.  We’ll return to that in a moment.
In a recent study researchers in Spain followed thousands of patients at sleep clinics and found that those with the most severe forms of sleep apnea had a 65 percent greater risk of developing cancer of any kind. The second study, of about 1,500 government workers in Wisconsin, showed that those with the most disordered sleep had five times the rate of dying from cancer as people without the sleep disorder (apnea not specified). Both research teams only looked at cancer diagnoses and outcomes in general.  If I lump the two studies, assuming that all patients with the most disordered sleep had OSA and were on CPAP, what does this tell us?  The heart and lung function together as a cardiopulmonary oxygenation unit!  A problem disrupting oxygenation, such as autonomically controlled sleep disruption or, oronasal obstruction (ASSOCIATED WITH SNORING), would be expected to have an effect on alertness during the day, predisposition to CHF from strain on the CP circulation as well as ventilatory impairment and peripheral oxygenation.  It appears that an association with ANY cancer, unspecified, is a long reach.
In both studies the researchers ruled out the possibility that the usual risk factors for cancer, like
  1. age
  2. smoking
  3. alcohol use
  4. physical activity
  5. weight
The association between cancer and disordered breathing at night remained
  • even after they adjusted for confounding variables.
This led to the conclusion that cancer might be linked to (intermittent) lack of oxygen supply interrupting aerobic cell activity over long periods of time.  The conclusion is drawn that from two associations
  • the research on positive outcome from CPAP in OSA and
  • a possible link between breathing and cardiac and cancer clearly
demonstrates the importance of regular breathing exercises (other wise known as ‘Pranayama’ in India) as part of our every day life.
This answers the first observation I posed. That is, the use of CPAP, while enormously important, is not sufficient.  Regular breathing exercises would seem to be helpful, although not a standard part of current treatment. This would be especially important if the movement of the abdominal muscles and diaphragm were synchronized with the expansion of the nthorax for maximum air flow.  This observation is familiar from working with a certified exercise physiologist.   The other part of this is an optimum time for walking and carrying out basic muscle and flexibility exercises several times a week, which has been shown repeatedly by studies on health benefits.
It is not my place to raise some questions about the way the studies were carried out.  The patients who have sleep apnea would be expected to have an increased body mass index (BMI), and while not sarcopenic, more likely to have excess body fat, abdominal distribution in males, and hip distribution in females, amd more importantly, unseen fat in the abdominal peritoneum.  This is related to type 2 diabetes with a metabolic syndrome, a separate indicator of CVD risk.   The metabolic syndrome involves TNF-alpha (once also known as cachexin), IL-1, IL-6, C-reactive protein, and in the case of fat signaling, adipokines, as well as insulin resistance and, as a result, some counter-regulatory secretion of glucocorticosteroids.  This metabolic picture would result in the following:
  1. impaired glucose utilization
  2. some excess and uncompensated gluconeogenesis
  3. the impaired lactate reentry at the end of glycolysis
  4. an effect on allosteric PFK
Features 1-4 look like what Warburg called a Pasteur Effect, not at the clellular level, but in the whole individual.   While obesity and type 2 diabetes are occuring in the young and adolescent population, the consequences might not be seen until years later.  The consequences could be in a middle aged person falling asleep at a meeting, or a series of automabile accidents related to falling asleep at the wheel.
At a time that clinical laboratory measurements are so accurate, and
  • the associations between type 2 diabetes,
  • measurement of wt/ht^2,
  • arm strength,
  • skin fold thickness,

are common measures of fitness, they don’t appear to have any place in these studies. If that is the case, then how is it possible to make sense of a relationship between SEVERITY of sleep disturbance and health outcome.

English: The Cycle of Obstructive Sleep Apnea ...

English: The Cycle of Obstructive Sleep Apnea – OSA (Photo credit: Wikipedia)

English: The graph shows the correlation betwe...

English: The graph shows the correlation between body mass index (BMI) and percent body fat (%BF) for men in NCHS’ NHANES III 1994 data. The body fat percent shown uses the method from Romero-Corral et al. to convert NHANES BIA to %BF (June 2008). “Accuracy of body mass index in diagnosing obesity in the adult general population”. International Journal of Obesity 32 (6) : 959–956. DOI:10.1038/ijo.2008.11. PMID 18283284. (Photo credit: Wikipedia)

English: Body mass index, BMI, body size, body...

English: Body mass index, BMI, body size, body weight, mortality Italiano: indice di massa corporea, IMC, altezza corporea, peso corporeo, mortalità (Photo credit: Wikipedia)

Italiano: biometria, epidemiologia, rischio, p...

Italiano: biometria, epidemiologia, rischio, peso corporeo umano, mortalità, indice di massa corporea, IMC, body mass index, BMI, prospective studies collaboration (Photo credit: Wikipedia)

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