Some studies have shown an association between moderate alcohol intake and a lower risk of dying from heart disease. Perhaps people who sip red wine have higher incomes, which tend to be associated with more education and greater access to healthier foods. Similarly, red wine drinkers might be more likely to eat a heart-healthy diet. Researchers have also suggested that red wine, in particular, might protect the heart, thanks to the antioxidants it contains.
Exercise can also boost HDL cholesterol levels, and antioxidants can be found in other foods, such as fruits, vegetables and grape juice. However, in a recently conducted Mendelian randomization study, Vu and colleagues reported that low-to-moderate alcohol consumption reduced triglyceride and LDL-c and increased HDL-c, in particular the HDL2-c subfraction. Interestingly, the researchers found a nonlinear effect of alcohol consumption on HDL2-c levels.
This supports the findings from other studies that the alcohol-induced changes in HDL-c do not fully account for the lower risk of CHD in moderate alcohol drinkers Mukamal Other risk factors that are surrogate markers of atherosclerosis and future CHD events, such as cIMT, also have been examined.
The relationship between alcohol consumption and cIMT was inconsistent. Some reports suggest that low-to-moderate alcohol consumption is associated with favorable effects in insulin sensitivity and glucose metabolism, key risk factors in the development of diabetes Greenfield et al. Increased insulin sensitivity, which is the opposite of insulin resistance, is associated with a reduced risk for the development of type 2 diabetes and CHD.
Several epidemiologic and randomized controlled studies have found alcohol consumption decreases coagulation factors such as fibrinogen, which is a CV risk marker at elevated levels Mori et al. In addition to being essential to the coagulation cascade, fibrinogen also may play a proinflammatory role in the development of certain CV diseases, including vascular wall disease and atherosclerosis Davalos and Akassoglou Platelets and their role in clotting also affect CV disease.
Altered platelet responses e. Anticlotting therapies are therefore the cornerstone of managing acute coronary syndromes. Not surprisingly, alcohol consumption has complex and varying effects on platelet function. On the other hand, significant daily alcohol consumption increases platelet aggregation and reactivity. Infection or other stressful events also can lead to immune-triggered platelet production, a condition called rebound thrombocytosis, which may occur immediately after withdrawal from both heavy and one-time heavy binge drinking Numminen et al.
Although highly individualized and dose dependent, alcohol use also can increase bleeding time i. The effects of alcohol consumption on inflammation are twofold. Lower doses are associated with reduced inflammation, as indicated by markers such as C-reactive protein and certain interleukins. Conversely, higher levels induce oxidative stress and a wide variety of inflammatory markers. Data from numerous types of research studies show that alcohol may alter levels of antioxidant enzymes and stimulate oxidative damage, and it may therefore be involved in the pathogenesis of many types of alcohol-induced diseases Ceni et al.
Another mechanism underlying the cardioprotective effects of low-to-moderate alcohol consumption and CHD in particular may be related to a phenomenon known as ischemic preconditioning, which produces resistance to the loss of blood supply and oxygen to organs or tissues.
In the heart, this would protect the heart muscle myocardium from subsequent, more prolonged episodes of restricted blood flow ischemia followed by injury when that blood flow returns to the heart called reperfusion injury or ischemia—reperfusion injury; Veighey and Macallister Ischemic preconditioning results in smaller infarct sizes, fewer and less severe arrhythmias, and prevention of endothelial cell dysfunction Veighey and Macallister During the ischemic phase, the flow of oxygen and nutrients to the tissues is reduced, most significantly to the heart, brain, and kidneys.
In contrast, during the reperfusion phase, despite restoration of blood flow, a series of dysfunctional biochemical and metabolic changes are initiated that lead to extensive accumulation of ROS.
ROS induce a number of changes. One is the opening of the mitochondrial permeability transition pore, which is formed in the mitochondria during ischemic incidents, contributing to reperfusion injury and cell death.
Others include recruitment of neutrophils white blood cells that are among the first inflammatory cells to respond during inflammation and dysfunction of the sarcoplasmic reticulum, which can affect calcium ion storage and release into muscle fibers. Alcohol may affect various mechanisms implicated in ischemic preconditioning.
Among these is the activation of mitogen-activated protein kinases MAPK signaling cascades. MAPKs are activated in response to stressful stimuli and help regulate apoptosis. There also is desensitization of the mitochondrial permeability transition pore, which can mitigate ischemia—reperfusion injury Walker et al. This in turn prevents the opening of the mitochondrial permeability transition pore Walker et al.
Figure 3 summarizes the potential mechanisms underlying the cardioprotective and adverse effects of alcohol consumption. This area of research was briefly outlined here; more comprehensive reviews on these mechanisms are available Krenz and Korthuis ; Mathews et al. Mechanisms related to the positive and adverse effects of alcohol on cardiovascular conditions, such as coronary heart disease and stroke as well as cardiomyopathy. Different mechanisms may be in effect depending on the dose, duration, and pattern of alcohol consumption.
Drinking patterns, and in particular a binge pattern of drinking and higher frequency of binge drinking, are associated with a heightened risk of CV conditions such as HTN, stroke, and MI, as well as sudden death or increased mortality after MI Leong et al. Binge drinking in younger individuals also may increase the risk of stroke. One possible mechanism for the binge-associated increased stroke risk is HTN.
However, at least in younger people, HTN prevalence is low, suggesting that other mechanisms may be involved. It has been debated whether beverage type has differential effects. Some investigators have suggested that drinking wine may offer more protection against CV disease because it contains polyphenols, such as resveratrol and flavonoids, which are micronutrients with antioxidant activity Tangney and Rasmussen However, among studies designed to examine the influence of beverage type, no differences have been found in CV disease outcomes or biologic markers, such as HDL-c Mukamal et al.
Differential associations of CV risk with certain beverage types such as wine instead have been attributable to other lifestyle factors e. Finally, in studies of people from certain Eastern European countries, investigators have failed to find a cardioprotective effect with any level of ethanol consumption Britton and McKee This suggests that alcoholic beverage type may be an important mediator, because in countries such as Russia, spirits are the alcoholic beverage of choice.
However, the negative associations between alcohol consumption and CV outcomes in these countries also may relate to pervasive patterns of binge drinking Leon et al. Investigators have used a variety of noninvasive tests to evaluate the acute effects of alcohol consumption on myocardial function and hemodynamics in healthy humans.
However, these changes were transient, with small changes from baseline. For example, in one study, the ejection fraction decreased by 4 percent after alcohol consumption Delgado et al. In another study by Lang and colleagues , however, the researchers noted a decrease in the maximum pressure developed by a ventricle at any given left ventricular volume, plotted as the end-systolic pressure dimension slope, as well as a decrease in the rate-corrected velocity of left-ventricular fiber shortening—and cardiac output was increased.
Most likely, the decrease in contractility was offset by corresponding decreases in afterload end-systolic wall stress , systemic vascular resistance, and aortic peak pressure, which maintained cardiac output. As a result, whether or how these findings generalize to older healthy people and those with CV disease is unknown. However, in an elderly community- based population i. These investigators found increasing amounts of alcohol were associated with mild alterations in cardiac structure and function, which were greater in women.
In addition, recent research indicates that this generation will potentially consume alcohol at higher rates than previous generations Barry and Blow Consequently, more research may be necessary to better understand the effects of alcohol consumption on the CV systems of older adults.
Certain arrhythmias, such as atrial fibrillation, may be the most serious consequence of consuming large amounts of alcohol, and in particular binge drinking. Larsson and colleagues have reported that binge drinking defined by these researchers as having more than 5 drinks on a single occasion was associated with an increased risk of new-onset atrial fibrillation.
Atrial fibrillation is one of the most common arrhythmias and is strongly associated with adverse CV events, such as stroke Conen et al. Results from retrospective studies enrolling adults ages 40—60 also have linked binge drinking to a heightened risk of sudden death Wannamethee and Shaper Alcoholic cardiomyopathy ACM is a heart-muscle disease found in individuals with a history of long-term heavy alcohol consumption.
There are no specific immunohistochemical or immunological biomarkers or other criteria for an ACM diagnosis Piano and Phillips Therefore, a key factor in diagnosing ACM is a long-term history of heavy alcohol abuse without CHD or other cardiac conditions such as inflammation of and damage to the myocardium, known as myocarditis. The proportion of cardiomyopathy cases attributable to alcohol abuse has ranged from 23 to 40 percent Piano and Phillips Recently, Guzzo-Merello and colleagues reported that, among patients with a dilated cardiomyopathy phenotype, 33 percent had ACM.
Both men and women can develop ACM. In humans, the exact amount and duration of alcohol consumption associated with development of ACM remains unknown. This suggests either protective or adverse interaction effects of genetic or lifestyle factors Piano and Phillips ACM patients can present with either diastolic or systolic dysfunction and may or may not have symptoms of heart failure.
When these patients are treated with standard heart failure therapies, they have good clinical outcomes and reduced mortality rates. Factors associated with poor outcomes e. Long-term heavy alcohol consumption induces adverse histological, cellular, and structural changes within the myocardium. As with other alcohol-induced pathologies, mechanisms contributing to ACM include oxidative stress, apoptotic programmed cell death, impaired mitochondrial bioenergetics and stress, derangements in fatty acid metabolism and transport, and accelerated protein breakdown; these will be discussed in the following sections.
These mechanisms contribute to the myocyte cellular changes that lead to intrinsic cell dysfunction, such as sarcoplasmic reticular dysfunction and changes in intracellular calcium handling and myocyte loss. However, modulatory influences related to drinking patterns, genetic susceptibility, nutritional factors, ethnicity, and gender also many play a role Piano and Phillips figure 4.
Pathophysiologic schema for the development of alcoholic cardiomyopathy ACM. As noted in the text, the exact amount and duration of alcohol consumption that results in ACM in human beings varies. The exact sequence of the development of ACM remains incompletely understood. Data from animal models and human beings with a history of long-term drinking suggest that oxidative stress may be an early and initiating mechanism.
Many cellular events, such as intrinsic myocyte dysfunction, characterized by changes in calcium homeostasis and regulation and decreased myofilament sensitivity, can come about due to oxidative stress. Variables in gray ovals represent potential mediating factors. At least in the myocardium, many adverse cardiac intracellular effects found after chronic alcohol consumption can be attributed to oxidative stress:.
Alcohol-induced inhibition of transport proteins responsible for transporting glutathione from cytosol into the mitochondria e. Sarcoplasmic reticulum dysfunction, which can lead to systolic dysfunction as well as a thickening of the heart muscle that can make ventricles larger, known as cardiac hypertrophy Bing et al. Changes in handling of intracellular calcium ions Zhang et al.
Depressed or disturbed mitochondrial function Pachinger et al. Decreased myofibrillar ATPase activity, which affects muscle contraction Hastillo et al. Decreased myofibrillar calcium sensitivity, which affects contractile force generation in the heart Piano et al. Contractile protein fragmentation and disarray Jiang et al. Fatty acid accumulation within intracellular organelles, which can include atypical storage of fat in heart tissue that can lead to dysfunction Beckemeier and Bora ; Hu et al.
In various biologic systems, oxidative stress can be measured or inferred by several biologic indexes. These can include measurement of antioxidant enzymes e.
Collectively, data from human and animal models suggest that alcohol may alter important components of the antioxidant defense system, such as levels of antioxidant substrates e. Evidence of oxidative stress is found after short periods of alcohol consumption 2 to 18 weeks , at least in animal models. These data suggest that antioxidant defense mechanisms that attempt to protect the heart against oxidative damage appear to be initiated soon after drinking alcohol.
Also, as noted below, data from other studies demonstrate the protective role of administered antioxidants, such as a synthetic compound that mimics the native superoxide dismutase enzyme, called a superoxide dismutase mimetic. This suggests a direct or indirect role for ethanol-mediated oxidative stress in the heart Jiang et al.
Data from transgenic animal models and pharmacologic approaches strongly support a role for ethanol-induced oxidative stress in CV disease. Using both pharmacologic and transgenic approaches, Tan and colleagues showed that administering an ROS scavenger a superoxide dismutase mimetic to mice receiving a diet high in ethanol for 2 months significantly reduced nitrative damage i.
In addition, there was no evidence of nitrative damage in mice bred to disrupt i. Both experimental approaches also prevented accumulation of ethanol-induced scarring collagen and fibronectin ; apoptotic cell death; and changes in the size, shape, and function of the heart after injury to heart muscle ventricular remodeling.
Other researchers have used genetic approaches i. One approach included overexpression of proteins such as insulin-like growth factor IGF-1 , which stimulates growth and cell proliferation and has antiapoptotic effects see Zhang et al.
In contrast to control mice, the IGF-1—expressing animals exhibited no evidence of changes in expression of antioxidant enzymes i. The findings suggest a protective effect of overexpression of IGF-1 in the transgenic animals Zhang et al. Apoptosis also may be an important mechanism in ACM and a consequence of oxidative stress. Apoptosis as evidenced by increased protein expression of two key proteins—one that promotes apoptotic cell death i.
Moreover, apoptosis was of a similar magnitude in the alcoholic and the hypertensive subjects. Researchers have found evidence of mitochondrial dysfunction or impaired bioenergetics related to alcohol consumption. This is not surprising, because mitochondria are a major target for free-radical injury. Dysfunctional mitochondria are less efficient, can become a source of ROS, and are more likely to initiate apoptosis Marzetti et al. Histological studies published several decades ago reported evidence of mitochondrial injury, such as mitochondrial enlargement and disorganization, increased number of mitochondria, mitochondriosis small mitochondria closely packed together , and an increase in lysosome-like structures that break down biomolecules in myocardial postmortem biopsy samples from people with a long-term history of heavy alcohol consumption Hibbs et al.
Differences among results from human studies may relate to small sample sizes, duration of drinking, and degree of myocardial dysfunction. Changes in mitochondrial function have been reported from a number of animal studies in different species, under various alcohol consumption paradigms ethanol in water or liquid diet , and after variable durations of chronic ethanol consumption 6 weeks to 6 months.
Common findings in alcohol studies from the s and early s included decreases in mitochondrial indices that reflected mitochondrial state III respiration, or ADP-stimulated respiration Pachinger et al. The latter changes in these indices could be brought about by ethanol-induced imbalances in the reducing equivalents nicotinamide adenine dinucleotide NAD and nicotinamide adenine dinucleotide hydrogen NADH , an important chemical pathway involved in oxidative stress.
In cardiomyocyte mitochondria as well as other mitochondrial types, such imbalances could lead to further decreases in cellular respiration and oxidative phosphorylation.
More recent studies have confirmed that 4 to 16 weeks of ethanol consumption was associated with mitochondrial dysfunction. This was evidenced by decreased myocardial ATP content levels, changes in the mitochondrial membrane potential, and decreases in cytochrome oxidase activity in conjunction with decreased myocardial contractility e. Although the connection is still speculative, this reduction in ATP synthesis may be enough to depress important intracellular functions that support heart health, such as sarcoplasmic reticulum uptake of calcium ions and cross-bridge cycling in muscle contraction.
Prolonged ethanol consumption also may decrease expression of several types of mitochondrial proteins, such as NADH dehydrogenase, isocitrate dehydrogenase, and long-chain-specific acyl-CoA dehydrogenase, as well as proteins within the citric acid cycle Fogle et al. This kind of mitochondrial dysfunction, including decreased expression of some of these proteins, is integral to cardiac ischemic—reperfusion injury, which occur routinely with MI—the most common incident of CV disease, itself the number-one cause of death Tompkins et al.
Derangements in fatty acid metabolism and transport and formation of fatty acid ethyl esters FAEEs also have been implicated in ethanol-induced cell injury. FAEEs can be formed in the body during ethanol metabolism, when ethanol reacts with fatty acids or triglycerides. FAEEs can attach to mitochondria and disrupt mitochondrial function. The idea that FAEEs are involved in ACM pathogenesis and are cytotoxic is supported by the fact that increased tissue levels of FAEE are considered the mechanism underlying cell death induced using a procedure to control and prevent recurrence of cardiac arrhythmias i.
Other researchers have confirmed in animal models that long-term ethanol consumption can also affect long-chain fatty acid LCFA uptake, as well as increased expression of the genes encoding for proteins involved in the formation of triglycerides from free fatty acids and glycerol, or triglyceride esterification, and in LCFA transporters Hu et al.
Long-term alcohol use decreases myocardial protein expression and synthesis and accelerates protein degradation in the myocardium Lang et al.
These investigators also found decreases in peroxiredoxin 5, antioxidant protein 2, and glutathione transferase 5—important antioxidant enzymes whose cardiovascular protective functions still are not fully understood.
For example, some findings suggest an inverse role between peroxiredoxin 5 and stroke severity. During a severe stroke, peroxiredoxin 5 is consumed and its production impaired Kunze et al.
Several reports suggest that ethanol-induced decreases in myocardial protein synthesis may be mediated in part by decreased activity of an enzyme called mammalian or mechanistic target of rapamycin mTOR Lang and Korzick ; Vary and Deiter ; Vary et al. Decreases in mTOR activation may play a role in reduced myocardial protein synthesis, ventricular wall thinning, and dilation. Alterations in protein physiology and content also can result from accelerated protein degradation.
The normal destruction of molecules and cell organelles called autophagy may be especially important in triggering ACM. Autophagy is performed by lysosomes and involves a breakdown catabolism of unnecessary or damaged proteins in the cell. This mechanism also is essential to cell and organism survival during stress and nutrient deprivation. Under the latter conditions, autophagy helps generate and recycle carbons and amino acids through degradation of large macromolecular cellular constituents.
However, as with other CV pathological conditions, such as heart failure and cardiac hypotrophy, there is evidence of increased autophagy with chronic alcohol consumption. Guo and colleagues studied autophagy in mice with and without an overexpression of the enzyme alcohol dehydrogenase to show that 8 weeks of ethanol consumption was associated with increased myocardial markers of autophagy, such as autophagy-related 7 protein. Increased autophagy as a possible mechanism underlying the adverse myocardial effects of ethanol is intriguing.
This is especially true in light of the relationship between a sensor of stress mTOR and nutrient deprivation and how essential autophagy is to cell survival. Activation of mTOR leads to inhibition of autophagy. As noted above, chronic alcohol exposure leads to a decrease in mTOR activity, which corresponds to increased markers of autophagy Lang and Korzick The autophagy pathway also is rapidly upregulated during ATP depletion, mitochondrial dysfunction, and oxidative stress.
Ethanol-mediated increases in autophagy therefore may be an important mechanism underlying the adverse myocardial effects of ethanol. Some of the potential cellular changes related to ethanol consumption reviewed above are illustrated in figure 5. More than one cellular event may be happening at the same time, and, as with other chronic health conditions, the relevant mechanisms may be synergistic and interrelated.
Summary of potential cellular changes related to ethanol. Ethanol-induced changes may be related to oxidative or nonoxidative pathways of ethanol metabolism. More than one mechanism may be activated and may lead to the multitude of ethanol-induced changes in cellular proteins and cell function.
As reviewed in the text, data from pharmacologic and transgenic approaches revealed an important role for oxidative stress and the hormone angiotensin II. Alcohol consumption remains a major risk factor for global burden of disease Rehm et al.
Nearly all the data on humans exploring the relationship between alcohol consumption and CV risk—including some indications of potential CV benefits associated with low-to-moderate alcohol consumption— are derived from epidemiologic studies.
Therefore, because there are no randomized controlled trials, health care professionals should not recommend alcohol consumption as a primary or secondary lifestyle intervention. Instead, clinicians should continue to recommend strategies such as a healthy diet and exercise. Adults who choose to drink can be encouraged to follow the alcohol consumption recommendations from NIAAA table 3.
No more than 4 drinks on any single day and no more than 14 drinks per week for men age 65 or younger. No more than 3 drinks on any single day and no more than 7 drinks per week for women and men over the age of Data derived from systematic reviews and meta-analyses suggest that alcohol-dose and CV-health relationships differ for various CV conditions.
For example, certain levels of alcohol consumption that lower risk for CHD may increase it for other CV conditions, such as stroke.
In addition, data from studies using new research methods, including Mendelian randomization, suggest that the relationship between low-to-moderate alcohol consumption and cardioprotection merits more critical appraisal Holmes et al.
The growing rate of binge drinking in the United States is a serious concern Kanny et al. ACM, though not a leading cause of heart failure nationwide, can be associated with marked changes in cardiac function, symptoms, and poor quality of life.
When clinicians are counseling patients about alcohol consumption, they should consider all these factors, as well as any history of alcohol dependence. Of course, any advice about alcohol consumption and related health issues needs to be targeted for each patient. Using direct biomarkers of alcohol, such as PEth, to corroborate self-report of alcohol consumption and distinguish between and among low, moderate, and heavy alcohol consumption.
Examining the potential mediation of genetic, socioeconomic, and racial and ethnic factors within the alcohol—CV disease relationship, specifically regarding development of ACM. As suggested by Klatsky , reviewing alcohol—medication interactions, considering the large number of antiplatelet agents, lipid-lowering, and antihypertensive therapies prescribed to people with CV conditions.
Examining the CV effects related to alcohol use in young adults ages 18—30 , a group that consumes the most alcohol and binge drinks the most. Considering the growing number of older adults, more research is needed to better understand the effects of alcohol consumption on the CV systems of older populations.
Because of space limitations, not all of the excellent scientific work on alcohol and the cardiovascular system could be assessed in this review. Some of the information presented here was previously published. For further detail, please see Piano or Piano and Phillips Accessed December 13, Each woman was given either no alcohol or 15 g of alcohol 1 standard drink with either a low-carbohydrate or a high-carbohydrate, high-fat meal. The researchers found that the alcohol-drinking subjects particularly those who were insulin sensitive had higher insulin levels and a slower rise in glucose levels after a low-carb meal.
They recommended confirming these results in younger women and in men, particularly since their subjects had been older women, who have more significant cardiovascular risk. They do not pass readily through cell membranes, and they are major components of very-low-density lipoproteins VLDLs , which are converted in the blood to LDLs. High levels of triglycerides in the blood have therefore been linked to atherosclerosis, heart disease, and stroke.
Financial Disclosure. National Center for Biotechnology Information , U. Journal List Alcohol Res v. Alcohol Res. Mariann R. Piano , Ph. Author information Copyright and License information Disclaimer.
Piano, Ph. Copyright notice. Unless otherwise noted in the text, all material appearing in this journal is in the public domain and may be reproduced without permission. Citation of the source is appreciated. To get a more accurate analysis of your drink in terms of alcohol content per serving size, use this drink calculator from the National Institutes of Health.
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