Support for aldosterone hypothesis

HOMBURG/SAAR, GERMANY. In my 2003 research report “Aldosterone: Villain of the Peace” I suggested that an elevated level of aldosterone could be instrumental in the initiation of an episode of lone atrial fibrillation[1]. A small trial involving myself and a curious nephrologist (kidney specialist) confirmed my speculation. My blood levels of aldosterone and cortisol were 50% and 107% higher on the day before an episode as compared to the day after an episode. Urinary potassium and magnesium losses were up 54% and 29% respectively when comparing values for the day before an episode with values on the day following an episode[2]. This supports the idea of aldosterone involvement, but it should be clearly borne in mind that the molecular structure of cortisol is such that it can “dock” at the same mineralocorticoid receptors as aldosterone and thus create the same effects.

Aldosterone production is usually initiated by activation of the renin-angiotensin-aldosterone system (RAAS) in response to a drop in blood pressure. However, it can also be initiated by ACTH, the same hormone that stimulates the secretion of the stress hormone cortisol. A high potassium level or a low sodium level also causes aldosterone secretion to be increased. A magnesium deficiency causes an increase in aldosterone production and subsequent hypokalemia (potassium deficiency). An excess of calcium ions (Ca++) can also increase aldosterone production because excess Ca++ increases the secretion of ACTH.

A group of German researchers now confirms that elevated aldosterone levels can facilitate atrial fibrillation (AF). Their experiment involved 43 Sprague-Dawley rats that were continuously infused with aldosterone for 8 weeks and 40 controls. At the end of the 8-week period aldosterone level was more than 4 times higher in the “aldo” rats than in controls and potassium level was reduced by 36%. An attempt was made to induce AF by transesophageal atrial burst stimulation. AF was induced in 11 of 11 (100%) aldo rats as compared to 2 out of 9 (22%) in the control group. There was a significant prolongation of p-wave duration in aldo rats (25.6 vs 20.1 ms) and the degree of interstitial fibrosis observed in the left atrium of aldo rats was more than double that observed in controls.

The researchers conclude that aldosterone creates an “AF friendly” substrate characterized by conduction disturbances, atrial fibrosis and myocyte hypertrophy without inducing hypertension. They also observed that aldosterone impeded the function of matrix metalloproteinase-13, the main enzyme responsible for fibrosis reversal in rats. They suggest that clinical trials are warranted to evaluate the effect of mineralocorticoid receptor antagonists (spironolactone and eplerenone) in the primary and secondary prevention of atrial fibrillation.
Reil, JC, et al. Aldosterone promotes atrial fibrillation. European Heart Journal, Vol. 33, 2012, pp. 2098-2108

Editor’s comment: The confirmation that elevated aldosterone levels and by implication, elevated cortisol levels, can create an afib-friendly environment is indeed of great interest as is the confirmation of the ability of aldosterone to create fibrosis in the atria. It should be kept in mind that aldosterone secretion can be initiated by ACTH, an important component in the hormonal cascade activated as a result of chronic stress. It is also worth noting that that many of the triggers implicated in setting off an episode impacts the autonomic nervous system which in turn may set off the stress reaction.

According to several LAF surveys stress (emotional or physical) is the single-most common trigger for afib episodes. It is particularly significant for adrenergic and mixed afibbers with over 90% of adrenergic and 56% of mixed afibbers listing emotional or work-related stress as an important trigger.

Stress is the body’s response to an event that upsets its normal balance (homeostasis). Stressors can be physical, emotional, chemical or biological. Examples of physical stressors are vigorous exercise, trauma, exposure to cold, and surgery. The most common chemical stressor, apart from adverse drug and food reactions, is hypoglycemia (low blood sugar). Emotional stressors run the gamut from anxiety to depression, fear of flying, an exam or other difficult mental task, fear of demotion or loss of job, marriage break-up, loss of a loved one, moving house, etc. In short, it can be anything that taxes you emotionally or gives you a gut feeling that something is not right. Bacterial and viral infections and fever are the most common biological stressors. Stress can be acute, like when you face a mugger in a dark alley, or chronic, like when you have to deal with an unreasonable boss every day.

There is evidence that spironolactone and eplerenone can reduce fibrosis formation in heart failure patients so it would seem plausible that these drugs (mineralocorticoid receptor antagonists) could do the same in the case of lone atrial fibrillation. As a matter of interest, an afibber reported in one of our early surveys that he had eliminated his afib through the use of eplerenone.

[1] Aldosterone: Villain of the Peace
[2] Results of aldosterone test