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Autonomic Balance and Coronary Plaque

The Greater the Variation, the Better

Chronic overstimulation and inadequate suppression of the sympathetic nervous system, the so-called “fight or flight” system, is common in people who develop coronary plaque. While fight or flight can serve us well when fleeing from a predator, the chronic stimulation associated with stress, metabolic syndrome and other insulin resistant states, inactivity, and other situations erode our sense of well-being and add to cardiovascular risk and atherosclerotic plaque growth.
 
Management of these phenomena, on the other hand, provides a potential additional means to further reduce our risk.
 
 
Sympathetic vs. parasympathetic: The yin and yang of the autonomic nervous system

Numerous body functions are under autonomic, or subconscious automatic, control. For instance, swallow a few blueberries and your esophagus automatically propels it down, the stomach senses the presence of chewed foods and releases gastric acid, the pancreas releases digestive enzymes and insulin, etc. All of this occurs below the level of consciousness and, thankfully, without your conscious thought or command. (Imagine what life would be like if it were not!)
 
Such phenomena are influenced by the two opposing “sides” of the autonomic nervous system: the sympathetic and the parasympathetic systems. The sympathetic system, the fight or flight system, is characterized by adrenaline release, increased heart rate, increased respiration, increased blood pressure, and bronchial (airway) dilatation to prepare the body for fighting off danger or fleeing. The parasympathetic system generates the opposite response, often called the relaxation response, of reduced heart rate, slowed respiration, reduced blood pressure, along with a sense of calm.
 
These opposing forces are meant to strike a balance in heart rate control. The sinoatrial node located in the right atrium of the heart generates a natural heart rate of approximately 105 beats per minute (bpm); however, most adults maintain a resting heart rate between 60-80 bpm due to parasympathetic suppression of rate. Elite athletes, due to their excellent cardiovascular conditioning, enjoy high parasympathetic tone evidenced by resting heart rates in the 40-60 bpm range.
 
Day to day life is a shifting tide of sympathetic and parasympathetic balance. The process of morning arousal, for instance, represents the circadian peak of involuntary sympathetic stimulation and involves a surge in adrenaline, increased heart rate, and increased blood pressure, as well as a modest increase in cardiovascular events (Muller 1999). Stressful situations allow sympathetic stimulation to dominate even after the “rush” of arousal passes, such as sleep deprivation, stimulant supplements or drugs, and multiple other factors (below).
 
 
When Sympathetic Tone Dominates

Both the sympathetic and parasympathetic systems provide necessary functions but need to exist in a balance appropriate for the situation. However, various degrees of autonomic imbalance are common. In particular, there are definable health consequences of high sympathetic tone coupled with low parasympathetic tone.
 
A number of simple observations point towards excessive sympathetic stimulation and low parasympathetic tone as unhealthy and associated with increased risk for cardiovascular events: 
  • People with faster heart rates have greater risk for heart attack and other cardiovascular events than those with slower heart rates (Gillman 1993). Increased risk for cardiovascular events begins at a resting heart rate of 75-80 bpm. (The most exaggerated displays of such phenomena are in people with autonomic neuropathies, i.e., complete or near-complete loss of parasympathetic tone. People with longstanding diabetes, for instance, can develop an autonomic neuropathy with near-complete absence of parasympathetic tone; these people have resting heart rates of 120-130 bpm and 5-year mortality rates as high as 27-53%; Vinik 2003.)
     
  • Inability to slow heart rate by 10 or more beats per minute with deep breathing (Katz 1999).
     
  • Failure to slow heart rate after exercise—The slowing of heart rate immediately after achieving a heart rate peak is a marker of parasympathetic tone and risk of cardiovascular events: the greater the slowing of heart rate in the first minute after exercise, the lower the risk for cardiovascular events (Nishime 2000). The failure to slow heart rate less than 12 beats per minute from peak while walking 1.5 miles per hour at 2.5% grade on a treadmill was associated with over 4-fold greater risk of death from heart attack.
     
  • All of the facets of insulin resistance have been associated with both measures of autonomic dysfunction as well as increased risk for cardiovascular events (Laakso 1996). Insulin resistance, from impaired fasting glucose to full diabetes, has been associated with increased resting heart rate, increased blood pressure, and decreased heart rate variability (see below).
     
  • Situations associated with increased sympathetic stimulation have all been uniformly associated with increased cardiovascular risk, including sympathomimetic agents like ephedra, phenylpropanolamine, ma huang, nicotine, and amphetamines, as well as beta-agonist inhalers used to treat asthma (Curtis 2002).
     
Chronic sympathetic overstimulation has been associated with other unhealthy phenomena, such as dangerous heart rhythm disorders, endothelial dysfunction, and hypertrophy of the left ventricle (Curtis 2002)
 
 
Heart Rate Variability: Window on Autonomic Balance
 
The observation that heart rate increases with inspiration and slows with expiration dates back as far as 1847, with the astute observations of German physiologist Carl Ludwig. Mid 20th century observations established that heart rate variability was abolished with administration of the drug, atropine, that essentially “turns off” parasympathetic function, as well as in diabetics.
 
The relationship of variation of heart rate with parasympathetic control is linear:

 
As parasympathetic control increases, heart rate period (time between heart beats) increases (i.e., heart rate slows). From Katona 1975.
 
 
While heart rate alone can serve as an index of sympathetic-parasympathetic balance, a superior measure is the variation in heart rate from moment to moment, the interval between each heart beat. More precisely, the variation in heart rate, or the beat-to-beat interval, as it tracks with respirations is among the most powerful measures of autonomic tone. Ideally, deep inspiration should trigger shortening of beat-to-beat variability (increased heart rate), while exhalation is associated with lengthening (slowed heart rate); the greater the variation—lengthening and shortening—the lower the cardiovascular risk, a phenomenon confirmed in numerous studies across multiple disease conditions.
 
 
Circadian variation of high-frequency heart rate variability is reduced in people with coronary disease. From Huikuri 1994.
 
 
As shown in the graph, people with coronary disease have less heart rate variability than people without coronary disease; circadian variation in heart rate variability is also markedly blunted (Huikuri 1994).
 
The Framingham Heart Study demonstrated that risk for development of angina, heart attack, congestive heart failure, and sudden cardiac death was strikingly higher over 3.5 years in participants with the least heart rate variability (Tsuji 1996). In people who have experienced prior heart attack, reduced heart rate variability has proven to be a substantial predictor of mortality, with up to 5-fold greater mortality in participants with the lowest levels (Kleiger 1987; La Rovere 1998). The relationship of coronary disease with reduced heart rate variability is magnified in the presence of depression (Carney 1995).
 
Another analysis from Framingham demonstrated that impaired fasting glucose (fasting glucose 110-125 mg/dl) and diabetes are associated with reduced heart rate variability (Singh 2000). Over three years of observation, diabetics were noted to experience 20% reduction in heart rte variability (Jokinen 2003). Reduced heart rate variability has also been associated with hypertension, high cholesterol, prior heart attack or stroke, and obesity (Berntson 1997). There is also an expected decline in various measures of heart rate variability in normal individuals with aging, with a 60% decline from age 20 to age 100 (Umetani 1998).
 
A study of 265 men who had previously undergone bypass surgery were assessed with coronary angiography; those with the least heart rate variability showed the most progression of disease over 32 months, while those with the most heart rate variability showed regression; a middle group with an intermediate degree of heart rate variability showed no progression (Huikuri 1999). Interestingly, the relationship of heart rate variability and coronary disease progression was abolished in participants taking gemfibrozil.
 
 
Increase Parasympathetic Tone, Restore Health
 
Studies applying heart rate variability as the biofeedback tool have shown that increased heart rate variability is associated with:
  • Reduced perception of stress and less depression (Nolan 2005).
     
  • Reduced systolic (-3 mmHg) and diastolic (-1 mmHg) blood pressure over 24 hours (Nolan 2010).
     
  • Improved exercise tolerance in people with heart failure (Moravec 2008).
     
While it has been established that lower heart rate variability is associated with several adverse health consequences, we still require further exploration of how much we can expect in health benefits by improving it.
 
 
A Do-it-yourself Approach to Restoring Parasympathetic Tone

There are a number of steps you can take immediately to assess your current autonomic balance or parasympathetic status.
 

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