Acute ingestion of alcohol can have many deleterious effects on the cardiovascular system and can cause noncompliance with medications. Tachycardia and elevated blood pressure are common effects of alcohol, perhaps due to vagal withdrawal. For example, Rossinen et al. (23) had 20 patients with stable exertional angina Holter-monitored while given either juice alone or juice mixed with 1.25 g of ethanol. The mean heart rate increased from 57 to 64 beats per minute, while the mean systolic blood pressures increased from 132 to 141 mm Hg.
Alcohol can also cause nonsinus arrhythmias (24). In a study by Greenspon and Schaal (25), 14 patients with a history of alcohol consumption and rhythm disturbance were given 90 ml of 80-proof whiskey. Ten of the 14 patients developed sustained or nonsustained atrial or ventricular tachydysrhythmias.
Chronic alcohol intake can lead to cardiomyopathy, leading to heart failure (26). In 1981, Matthews et al. (27) reported that of 22 asymptomatic chronic alcoholics, 15 (68%) had echocardiography changes consistent with alcoholic cardiomyopathy.
Heart failure in the alcoholic is thought to happen in many distinct ways. Arrhythmias may precipitate heart failure, particularly atrial fibrillation, after an acute episode of alcohol ingestion. Atrial fibrillation deprives the left ventricle of the left atrial contribution to cardiac output, which can be significant in individuals who are barely compensated. Second, there is the alcoholic cardiomyopathy, the mechanism of which remains to some extent obscure. Third, nutritional deficiencies can result in conditions such as beriberi, which can have important cardiac manifestations. Fourth, contaminants can occasionally be cardiotoxic, as in the case of the outbreak of cardiomyop-athy in Canada as a consequence of excessive cobalt in beer (28). Chronic hypertension, which may be related to alcohol use, leads to left ventricular hypertrophy, which can proceed to congestive heart failure. Finally, the drinker may develop "cirrhotic" cardiomyopathy. The proposed mechanisms of heart failure due to alcohol are shown in Table 2.
Alcoholic cardiomyopathy is a dilated cardiomyopathy and is not uncommon. Alcoholic cardiomyopathy in the absence of vascular disease and
Table 2. Mechanisms of Alcohol-Associated Heart Failure
Type of heart failure in alcoholism Mechanism
1. Alcohol heart muscle disease
2. Atrial fibrillation
3. "Wet" beriberi (thiamine deficiency)
4. Contaminant cardipmyopathy
5. Cirrhotic cardiomyopathy
Decreased myocardial protein synthesis, free radical damage to myocardium Decreased contribution to cardiac output from atrial contractions "High-output" state with decreased systemic vascular resistance Contaminants in alcoholic beverage directly toxic to myocardium A "high-output" state similar to thia-mine deficiency, featuring decreased systemic vascular resistance Chronic hypertension causing left ventricular hypertrophy and diastolic dysfunction malnutrition has been called alcohol heart-muscle disease (AHMD) (29). It is thought that ethanol exerts a dose-related toxic effect on cardiac muscle, and, as with alcoholic liver disease, women are perhaps more susceptible to this effect than men (30). There are probably a number of factors that may contribute to individual susceptibility to this phenomenon, including hypertension, smoking, established cardiac disease, disorders of the immune system, and genetic differences in alcohol metabolism (29).
The toxic effect of alcohol on the myocardium may be direct or indirect. Alcohol is metabolized to acetaldehyde, and acetaldehyde is in turn metabolized to acetate. These metabolites are thought to be cardiotoxic in their own right; for example, it has been demonstrated that both alcohol and acetalde-hyde reduce the Na+,K+ -activated ATPase activities of the myocardial plasma membranes in vitro (31). They also damage other organs and cause metabolic disarray. Preedy et al. (29) demonstrated that alcohol ingestion reduces the rate of synthesis of cardiac mixed and myofibrillary proteins. They measured myocardial protein synthesis in rats 2-5 hours after intraperitoneal injections of ethanol and found a decrease of 22%.
Beriberi, or thiamine deficiency, is unusual because the vitamin is present in so many foods. It is possible in alcoholic patients, however, because s alcoholism can lead to decreased dietary intake and defective absorption of the thiamine. The two disease states, thiamine deficiency and AHMD, are not =3
identical, however. They both feature chamber dilation, tachycardia, elevated venous pressure, and peripheral edema; it is important to note, however, that the alcoholic cardiomyopathy is a low-output state, whereas beriberi is a high-output state (32). The cardiac output (stroke volume x heart rate) is elevated in beriberi because peripheral vascular dilation is prominent in the disorder, resulting in tachycardia; in alcoholic cardiomyopathy, there is depressed cardiac output due to decreased myocardial contractility (33). When thiamine deficiency occurs, there is usually a mixed clinical picture, featuring Wernicke-Korsakoff's, "wet" beriberi (congestive heart failure), and "dry" beriberi (peripheral neuropathy) (34).
There is yet another entity in the cardiomyopathy encountered in alcoholics: the so-called "cirrhotic cardiomyopathy." Like beriberi, cirrhotic car-diomyopathy is a high-output cardiac state, with increased heart rate and decreased systemic vascular resistance. It is not seen exclusively in alcoholic cirrhosis. The mechanism of this entity has not been fully elucidated, but impairment of the beta-adrenergic receptor has been proposed (35).
An ethanol intake of as little as 30-40 g/day (approximately two to four beers) can have a pressor effect. The effect abates within several days of achieving abstinence. The manner in which this effect is mediated remains obscure. Acute ingestion does not alter plasma concentrations of renin, adrenaline, noradrenalin, aldosterone, or cortisol, and there is no evidence of activation of the sympathetic nervous system (36). It is possible that in some heavy drinkers who are chronically hypertensive, the hypertrophic, less compliant left ventricle could evidence diastolic dysfunction, indirectly leading to yet another type of heart failure.
Excessive alcohol intake can, as noted, precipitate atrial arrhythmias— holiday heart syndrome, a syndrome of supraventricular tachydysrhythmias classically caused by a period of heavy alcohol use, usually manifests itself as an acute-onset episode of atrial fibrillation (38). Typically the atrial fibrillation reverts spontaneously to sinus rhythm within 24 hours. Other rhythm disturbances seen in this setting include atrial flutter, premature atrial contractions, and junctional tachycardia.
Ethanol is a common cause of secondary hypertriglyceridemia, usually a Type IV or V hyperlipidemia. It is second only to diabetes mellitus as a cause of hypertriglyceridemia (16). Moderate users usually have significantly higher triglyceride levels than abstainers. Withdrawal of alcohol leads to a rapid decrease in triglyceride levels. HDL levels are also elevated in ethanol users, g such that elevations in HDL, triglycerides, and GGT are virtually diagnostic s for alcohol use (39). •!,
In drinkers, partial sleep apnea may be converted to total sleep apnea, =3
especially if they consume alcohol in the evening hours. Sleep apnea can result g in chronic hypoxemia and hypercapnea, with respiratory acidosis and poly-cythemia. These conditions can in turn lead to pulmonary vasoconstriction and pulmonary hypertension (40). Pulmonary hypertension can in time lead to right-heart failure with hepatic congestion and lower-extremity edema.
There is evidence that long-term exposure to alcohol can result in a Cushingoid appearance with central obesity, plethora, striae, and hypertension. It has been called "alcohol-induced pseudo-Cushing's syndrome" (41). Hypertension, no matter what the cause, is one of the most important risk factors for coronary artery disease.
The question of whether alcohol is contributory or causative in cerebral infraction is complicated by the fact that a high percentage of heavy drinkers are also smokers. The evidence that alcohol alone may precipitate stroke is overwhelming, but evidence exists for alcohol acting in combination with other factors to cause cerebral infarction (42). You et al. (43) found the odds ratios for cerebral infarction to be 11.6 for diabetes, 6.8 for hypertension, 2.7 for heart disease, 2.5 for smoking, 15.3 for long-term heavy drinking (greater than or equal to 60 g ethanol or four to five beers per day). These findings were in 201 first-stroke patients aged 15-55 years. For ischemic stroke, alcohol appears to demonstrate the J-shaped curve, indicating that moderate users have lower risk of stroke than abstainers and heavy users. By contrast, the influence on risk of hemorrhagic stroke is an increase with increasing consumption throughout the spectrum of usage patterns (44). In 1996 Camargo (45) published a review of the epidemiological data, concluding that while alcohol exhibited a J-shaped curve with respect to effect on ischemic stroke, and increased the risk of hemorrhagic stroke at all usage levels, the overall effect is to inhibit stroke, since 80% of strokes are ischemic.
Alcohol may contribute to the risk of stroke by several mechanisms. First is the well-known pressor effect of alcohol. Alcoholics may also develop deep venous thromboses (prolonged stasis), which may embolize to the brain if the patient has a communicating defect of the heart, especially ventricular septal defect (VSD). Alcohol has been demonstrated to activate the clotting cascade in vitro (42), although in vivo the effect is likely to be invisible to lower dosages. We have already noted that alcoholic cardiomyopathy is a dilated cardiomyopathy, and in such patients mural thrombi are not uncommon. "Holiday heart" dysrhythmias include atrial fibrillation, usually transient; such patients may form small atrial thrombi while their atria are fibrillating, and when the dysrhythmia resolves the thrombi are embolized (46).
Other possible mechanisms of brain infarction include infectious vas-culopathies associated with alcohol use, obstructive sleep apnea caused by or worsened by alcohol, and hypoxia due to alcohol-induced vasoconstriction.
Table 3. Mechanisms of Stroke Due to Alcohol
Alcohol-induced hypertension Embolic phenomena Alcohol-induced coagulopathy Dysrhythmias Infectious vasculopathies Trauma to vascular structures
Finally, trauma is common in intoxicated individuals; according to U.S. Department of Justice statistics, 40.9% of traffic fatalities are alcohol-related and 40% of violent offenders report drinking at the time of the offense (47). Physical assaults and motor vehicle accidents may result in direct damage to arteries, provoking arterial dissection, including of the carotids. Such injuries reduce flow and may have thrombosis and/or embolus as a result of intimal injury (42,46,48). Trauma to the cranium may also result in intracranial hemorrhage as a result of shear injury on intracranial vascular structures. Mechanisms of stroke due to alcohol are shown in Table 3.
Alcohol, especially red wine, has been suspected to be a causative agent in dietary migraine (49). Littlewood et al. (50) disguised red wine and vodka in appearance and taste, and challenged red-wine-sensitive migraineurs (keeping alcohol content equal); they found that nine of 11 of those who received red wine developed migraines but none of the eight vodka recipients did. Proposed mechanisms include stimulation of this release of serotonin (51), which is thought to be a precipitator of migraines, and inhibition of mono-amine oxidase, which would increase 5-HT levels. Of note, in Littlewood's study, the diluted red wine had "negligible tyramine content." Jarman, Glover and Sandler (52) demonstrated that serotonin was released from platelets exposed to red wine, but not those exposed to white wines or beer.
Overall, the cardioprotective effect of alcohol at certain doses must be put into context of the general risk/benefit to patients. Alcohol is the most common substance of abuse dependence, causes many accidents, and has direct deleterious effects such as CNS toxicity.
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