Alcohol is the most consumed drug in human history and its consumption rates are still very high. Research indicates that there is an increased use in particular groups, such as adolescents and young people.
This alcohol misuse at high consumption rates causes a variety of health problems, alcohol being the sixth most relevant factor of global burden of disease and
responsible for 5.3% of all deaths.
Despite this clear epidemiological evidence of alcohol’s unsafe consumption and increased health risk, consumption policies have deemed not to be adequately effective.
Alcohol has been described as the “perfect drug” because of its pleasant effects but damaging long-term effect.
It is distributed worldwide, with easy social access, and is pleasant when consumed, with positive sensations of welfare, but its destructive effects, which include depressive and damaging harmful health effects, are reserved for later.
This dual effect creates a huge boundary to achieve an effective control. Alcohol is one of the most addictive drugs for humans, with high physical and psychological addiction potential(1).
Despite the resources dedicated and effort put forth to control alcohol addiction; there is only about 50%–60% positive results in specific cessation programs(2).
It has some kind of an effect in all human body organs either in acute or chronic consumption(3).
The liver is the most affected organ, since alcohol is mostly metabolized there, but gastrointestinal, central, and peripheral nervous systems; the heart and vascular system; endocrinological systems; nutrition; and
musculo-skeletal systems are also clearly affected(4).
In addition, alcohol is an immunosuppressive drug that is pro-inflammatory and pro-oncogenic (i.e., cancer causing)(5).
The cardiovascular system is, after the liver and gastrointestinal system, the second most affected system by global alcohol toxicity(6).
At a high dose (more than 60 g/day for men and 40 g/day for women) and chronic consumption (usually more than 10 years), alcohol increases the atherosclerosis process with coronary, cerebral, and peripheral vascular involvement, increases arterial hypertension, and causes progressive myocardial damage (alcoholic dilated cardiomyopathy) as well as induction of arrhythmias(7)
In this article, we’ll examine the global effects that alcohol exerts on the heart myocytes, the so-called alcoholic cardiomyopathy.
Alcoholic Cardiomyopathy is defined as a dilated cardiomyopathy of toxic origin with low left-ventricle ejection fraction, chamber dilatation (i.e., enlarged beyond normal dimensions), and progression to congestive heart failure(8).
Excessive alcohol consumption is one of the main causes of non-ischemic dilated cardiomyopathy, representing around one-third of cases(9).
At clinical level, the course of alcoholic cardiomyopathy is similar to idiopathic dilated cardiomyopathy. An individual with excessive alcohol consumption, after more than 10 years of high alcohol consumption, usually develops subclinical heart functional changes before symptom appearance or signs of heart failure(10).
In addition to developing heart damage,
patients with alcoholic cardiomyopathy may also damage other organs, such as the liver, central and peripheral nervous system, skeletal muscle, pancreas, and
digestive tract, and are exposed to an increased risk of cancer(11).
Mortality in alcoholic cardiomyopathy is related to the progression of heart failure and malignant arrhythmias.
In long-term follow-up studies, a mortality rate of 10% of patients/year has been observed in the group of patients with persistent high-dose alcohol consumption.
There was no scientific evidence on the direct and dose-dependent effect of alcohol on the heart as cause of alcoholic cardiomyopathy until the second part of the 20th century. This is a long-lasting accumulated effect that usually appears when someone has, in their lifetime, consumed more than 7 kilogram of ethanol per kilogram of body weight in men (equivalent to
60 drinks per month, or two per day), and 5 kilogram of ethanol per kilogram of body weight in women (equivalent to
43 drinks per month, roughly 1.5 per day)(12).
However, there is a clear personal susceptibility of this effect that creates a wide variability range and supposes
significant inter-individual differences.
In fact, alcoholic cardiomyopathy is the result of dosage and individual predisposition(13).
Alcoholic cardiomyopathy may develop through the consumption of any type of beverage, such as wine, beer, or spirits, in a direct dose-dependence relationship with the total lifetime dose of alcohol consumed by an individual(14).
In general, alcoholic patients consuming >90 g of alcohol a day (approximately seven to eight standard drinks per day, considering a standard drink 12–15 g of alcohol) for >5 years are at risk for the development of asymptomatic alcoholic cardiomyopathy(15).
Wine is considered less damaging compared to other alcohol beverages, essentially because of its antioxidant polyphenolic content, with molecules such as resveratrol. Consuming spirits which have a higher alcohol content may easily induce binge drinking and higher cumulated lifetime dose of alcohol, increasing the risk of alcoholic cardiomyopathy(12).
Moderate drinking, considered as the consumption of 20–60 g/day in men (1.5–4 standard drinks) and 10–40 g/day in women (1–3 standard drinks), is typically not associated with significant cardiotoxicity(12).
It does not suppose a risk to alcoholic cardiomyopathy unless consumed over a large period of time (more than 10 years). Consuming alcohol moderately is associated with lower risk of heart failure in prior studies of healthy individuals(16).
Binge drinking, defined as the consumption in men of five or more drinks and four or more drinks in women in about two hours, is clearly detrimental for the heart. Acute alcohol binge drinking also induces a variety of arrhythmias, known as “Holiday heart Syndrome”(17).
All these acute effects produce impairments on the natural course of chronic alcoholic cardiomyopathy. Spirits and other beverages containing a high percentage of alcohol are more detrimental than wine consumption concerning the induction of acute cardiac effects(18).
Low-dose alcohol consumption, considered as the daily consumption of up to one standard drink for women and two standard drinks for men, has a beneficial effect on preventing coronary heart disease, heart failure, and global mortality as assessed in multiple clinical and epidemiological studies(7).
However, if someone is susceptible, there is potential for someone consuming low-dose alcohol to achieve an accumulated lifetime dose of alcohol reaching the threshold level required to develop acute cardiomyopathy.
This is especially possible in those patients more sensitive to the
toxic effects of alcohol on the heart, such as women and patients with other systemic diseases related to alcohol (cirrhosis, malnutrition, or neurological damage).
In addition, there are genetic propensities associated with vulnerability to alcoholic cardiomyopathy.
Therefore, there is no safe dose of alcohol consumption to completely avoid the development of alcohol cardiomyopathy, with complete abstinence being recommended in susceptible subjects(19).
In the course of alcohol-induced cardiac damage, one of the more relevant findings is that alcohol exerts its deleterious effects on cardiac myocytes at multiples sites (membrane, receptors, mitochondria, ribosomes, sarcolemma, DNA, or cytoskeleton)(12).
This occurs because the ethanol molecule has a small size and is highly reactive with many cell targets.
In addition, ethanol has a widespread diffusion because of the potential for distribution though biological membranes, achieving targets not only in the membrane receptors and channels but also in endocellular particles and at the same nuclear compartment(20).
This induces a variety of effects since more than 14 different sites in the myocyte can be affected by ethanol. The resulting effect in those multiple sites may be additive and synergistic, increasing the final damage(16) (see descriptive figure below)
Figure: Different effects of ethanol on cardiomyocyte organelles. (Adapted from Nature 2008)(21). Cardiac myocytes are excitable cells with complex signaling and contractile structures and are highly sensitive to the toxic effect of alcohol on: (1) plasma membrane composition and permeability, signaling, and activation of apoptosis; (2) L-Type Ca2+ channel activity; (3) Na+/K+ ATPase channel activity; (4) Na+/Ca2+ exchanger activity; (5) Na+ channel currents; (6) K+ channel currents; (7) ryanodine Ca2+ release; (8) sarcomere Ca2+ sensitivity, excitation–contraction coupling, myofibrillary structure, and protein expression; (9) several aspects of mitochondrial function, including respiratory complex activities; (10) cytoskeletal structure; (11) nuclear regulation of transcription; (12) ribosomal protein synthesis; (13) desmosomal contacts; (14) connexin channel communication; (15) sarcoglycan complex interactions.
Since alcohol consumption is not currently under control within the global population, the incidence of alcoholic cardiomyopathy is expected to be maintained in the future, especially in specific population groups, such as adolescents and young people(22).
Therefore, efforts for the prevention, early detection, and specific treatment in this relevant disease should be established.
The direct dose-dependent effect between alcohol intake and development of alcoholic cardiomyopathy is clearly established, women being more sensitive than men to the toxic effects of ethanol on the heart(23).
However, genetic polymorphisms, the use of other concomitant drugs (tobacco, cocaine), and the presence of other cardiac risk factors (hypertension, diabetes) may influence and worsen the natural course of alcoholic cardiomyopathy in each specific individual(24).
The multiple sites of myocyte damage from ethanol and the genetically mediated individual predisposition create a large individual clinical variability and make it complicated to establish a simple effective treatment for alcoholic cardiomyopathy.
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