Excessive Alcohol Consumption and Hypertension: Clinical Implications of Current Research

Abstract

Substantial evidence demonstrates that: 1) heavy alcohol consumption (three or more standard drinks per day) is associated with and predictive of hypertension; 2) reduction in alcohol consumption is associated with a significant dose‐dependent lowering of mean systolic and diastolic blood pressure; and 3) physician advice can reduce heavy drinking in hypertensive patients. These findings suggest that the routine evaluation of alcohol consumption in hypertensive patients is warranted. The Alcohol Use Disorders Identification Test‐C (AUDTT‐C), a brief, three‐question screening test, is useful in this regard. Alcohol biomarkers can also play a role in detecting and monitoring heavy drinking in hypertensive patients whose self‐reports on the AUDTT‐C are suspect. Carbohydrate‐deficient transfer‐rin, a new alcohol biomarker with high specificity, can provide objective data for feedback and counseling. A routine search for excessive use of alcohol, along with brief interventions and monitoring, can have a major impact on reducing the prevalence of hypertension in the general population.

As the most common primary diagnosis in the United States, hypertension affects approximately 30% of the population and more than one half of people over the age of 60. ¹ , ² An additional 22% may be prehypertensive. Hypertension is the leading cause of stroke and congestive heart failure and the second most common contributor to end‐stage renal disease. ²

Recent evidence suggests that light‐to‐moderate alcohol consumption is associated with a reduction in the risk of total and cardiovascular disease mortality in hypertensive men. ³ The seventh as well as several of the other reports of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommend that hypertensive patients limit alcohol intake to no more than two drinks per day for men and one drink per day for women. ²

Excessive alcohol consumption (three or more drinks per day) increases blood pressure (BP) significantly in normotensive and hypertensive patients and is strongly linked to hypertension. ⁴ Even in young patients with prehypertension or stage 1 hypertension, daytime diastolic BP variability is significantly increased in heavy drinkers, even after adjusting for smoking. ⁵

A national consensus panel in Canada recently conducted a comprehensive review of the alcohol–hypertension literature and found overwhelming evidence of an association between excessive alcohol consumption and increased BP in both men and women, independent of the factors of obesity and smoking. ⁶ Among middle‐aged men, a link exists between heavy drinking and an increased risk of stroke that is largely related to the effects of alcohol on BP. ⁷ In addition, heavy alcohol consumption appears to be a major contributory factor to heart failure in hypertensive patients. ⁸

Investigations of the relationship between bio‐markers of heavy alcohol consumption and hypertension corroborate epidemiologic and clinical studies that are based exclusively on self‐reports. The advantage of alcohol biomarkers is that they provide a more objective measure of excessive drinking than uncorroborated self‐reports, which are notoriously inaccurate in health care settings. Studies demonstrating a correlation between both gamma glutamyltransferase (GGT) and mean corpuscular volume and alcohol‐induced hypertension date back to the early 1980s. ⁹ More recent studies support these findings and also show a positive relationship between hypertension and carbohydrate‐deficient transferrin (CDT), a newer alcohol biomarker that is more specific than GGT or mean corpuscular volume in the detection of heavy alcohol use (CDT is currently available from select reference labs and, over time, will be more widely available). ¹⁰

BP readings, as well as the incidence and prevalence of hypertension, are significantly higher in patients with serum GGT levels >50 IU/L than those with levels ≤50 IU/L, independent of body mass index (BMI). ¹⁰ GGT is also predictive of future hypertension, suggesting that serum GGT levels may reflect individual susceptibility to the BP‐raising effects of alcohol; however, the mechanisms underlying GGT as a predictor of hypertension require clarification.

In a large investigation of more than 8000 men, BP and risk of hypertension increased over a 4‐year period as a function of the amount of alcohol consumed ¹¹ ; however, the link between BP and GGT was only evident when GGT was ≥30 IU/L. Risk of hypertension was similar to nondrinkers in individuals with a GGT of <30 IU/L. Among people with GGT levels ≥30 IU/L, the adjusted relative risk for hypertension for light, moderate, and heavy drinkers compared with nondrinkers was 1.4, 5.2, and 5.3, respectively.

AMOUNT AND PATTERN OF HEAVY DRINKING AND BP

The INTERSALT ¹² study, a large international BP investigation involving more than 10,000 men and women, examined the influence of the amount and pattern of alcohol consumption, as well as the chronic effects of drinking on BP. Results indicated that more than three to four standard alcoholic drinks—a standard drink is defined as 12 oz of beer, 5 oz of wine, or 1.5 oz of liquor—per day is the level at which drinking becomes strongly associated with higher BPs, after controlling for body mass index, smoking, and urinary excretion of Na and K.

This study also found that heavy drinkers with great variation in their daily alcohol consumption (i.e., episodic or binge drinkers) showed the greatest variation in BP, compared with abstainers or even daily heavy drinkers. Indeed, ambulatory BP demonstrated a rapid onset/offset of elevated BPs in weekend drinkers, with baseline ambulatory BP being 2.4 mm Hg higher on Monday than on Thursday. ¹³ These findings may explain why binge drinking appears to be a risk factor for stroke, especially in young adults who are more likely to be heavy weekend drinkers. ¹⁴

Finally, heavy drinkers have high BP whether they have consumed alcohol over the previous 24 hours (possible acute effects) or not (possible withdrawal effects), implying a sustained effect of chronic alcohol consumption on BP. ¹² The type of beverage consumed is not independently associated with the BP levels. ¹⁵

Recent evidence also suggests that drinking outside of meals appears to have a significant effect on hypertension risk, independent of the amount of alcohol consumed. ¹⁶ Drinkers who consumed alcohol separately from food had a 64% greater risk of hypertension. The most plausible speculation concerning this relationship relates to the beneficial effects of the food–alcohol interaction on slowing the absorption and metabolism of alcohol. ¹⁷

MECHANISMS FOR THE HEAVY DRINKING–BP CONNECTION

The specific physiologic relationship between heavy drinking and hypertension is not clear; however, factors contributing to this relationship are the acute pharmacologic effects of alcohol, autonomic hyperactivity associated with a chronic state of withdrawal, possible alcohol–medication interactions, and the effects of alcohol on compliance with medication and lifestyle recommendations.

Acutely, alcohol increases sympathetic nervous system activity that constricts blood vessels and increases the contractile force of the heart. ¹⁸ Studies in humans indicate that the initial direct effect of alcohol is vasodilation, with secondary stimulation of the sympathetic nervous system and vasoconstriction. ¹⁹ In addition, alcohol decreases sensitivity of baroreceptors in the artery walls, reducing signals to the central nervous system that are required to normalize BP. ²⁰ Finally, alcohol reduces the ratio of ionized Mg to ionized Ca in plasma, resulting in an increase in BP as the vessels contract. ²¹ Other possible mediators for a rise in BP include stimulation of the renin‐angiotensin‐aldosterone system; stimulation of endothelin, insulin, or cortisol; and increased acetaldehyde. ²² Still another hypothesis is that the hypertensive effect of alcohol is related to autonomic reactivity associated with a chronic state of alcohol withdrawal often seen in heavy drinkers. ²² However, in spite of these potential mediators, data from the INTERSALT study suggest that neither acute pressor effects nor alcohol withdrawal before BP measurement offer the major explanations, since heavy drinkers have higher BPs than nondrinkers whether they have consumed alcohol over the previous 24 hours or not. ¹²

Heavy alcohol use may be one cause of treatment‐resistant hypertension, since alcohol may interfere with the pharmacologic action of antihypertensive agents. For example, alcohol opposes the effects of clonidine, resulting in a decrease in the antihypertensive properties of this medication. ²³ Alcohol and diuretics might combine to reduce Mg concentration below physiologic levels, thereby counteracting the BP‐lowering effects of these drugs.

Heavy drinking also may interfere with adherence to physician recommendations designed to lower BP. Indeed, heavy drinkers are less likely than abstainers or moderate drinkers to comply with their BP medication regimen or to engage in lifestyle changes (e.g., reduced salt intake) to lower BP. ²⁴

GENETIC INFLUENCES ON THE ALCOHOL–BP INTERACTION

It may be that some drinkers are genetically susceptible to the pressor effects of alcohol on BP. Since alcohol consumption is known to affect BP through the β‐adrenoreceptor‐guanine nucleotide protein system, a possible interaction between GNAS1 T393C polymorphism may exist. Preliminary evidence suggests that the T393C polymorphism significantly interacts with drinking status in association with systolic BP and pulse pressure. ²⁵ Takashima and colleagues ²⁶ attempted to clarify the interactive effects of alcohol intake and angiotensinogen gene codon 174 (T174M) polymorphisms on BP. Findings showed that high‐normal BP prevalence (adjusted for age, body mass index, smoking, and Na intake) was significantly greater in TM or MM genotype categories than TT type, in subjects with ≥13.7 g of daily alcohol intake. No difference in this parameter was found between the two genotypes in those with <13.7 g of daily intake. Finally, several studies have demonstrated genetic differences in ethanol‐metabolizing enzymes (e.g., CYP2E1, ADH2, ADH3, ALDH2 genes) and their impact on BP. ²⁷

DOES REDUCING ALCOHOL CONSUMPTION DECREASE BP?

Since heavy drinking can cause or exacerbate hypertension, it would follow that reductions in alcohol consumption should reduce BP. Overall, studies indicate that each one standard drink reduction in intake per day reduces systolic and diastolic BP by about 1 mm Hg. ²²

In a recent meta‐analysis of 15 randomized controlled trials, alcohol reduction was associated with a significant reduction in mean systolic and diastolic BP of −3.31 mm Hg and −2.04 mm Hg, respectively. ²⁸ A dose‐response relationship was found between mean percent alcohol reduction and mean BP reduction. Decreases in alcohol consumption had the most effect on people with higher baseline BP. The INTERSALT study, ¹² with 10,000 subjects, showed similar BP reductions in people with high BP based on an average reduction of 67% in alcohol consumption. Overall, mean decreases in BP of the magnitude reported in these studies can substantially decrease the risk of hypertension and associated cardiovascular disease in the general population.

A notable exception to these positive findings is the Prevention and Treatment of Hypertension Study (PATHS), ²⁹ a large, randomized control trial with Veterans Administration patients that found only −0.9 mm Hg systolic and −0.6 mm Hg diastolic differences in BP as a function of reduction in alcohol consumption. In this well publicized trial, however, both baseline levels of alcohol consumption and, importantly, changes in alcohol intake were lower than in the majority of other clinical trials (i.e., an average reduction of only 1.3 drinks per day) and drinking diaries were not confirmed by biologic markers.

CAN PHYSICIANS INFLUENCE HYPERTENSIVE PATIENTS TO DECREASE DRINKING?

Primary health care is a natural setting for screening and intervening with alcohol‐related hypertension problems, since the majority of the population seek treatment for all kinds of medical conditions on a yearly basis. ³⁰ More to the point, hypertension is the number one diagnosis in primary care and is a chronic illness for which patients may see their providers regularly every 3–6 months.

In addition, advice by physicians about reducing excessive alcohol use is well received by patients. ³¹ The medical setting appears to make it easier for patients to respond positively to frank discussions of alcohol and health. ³² Physicians and nurses report that they feel more comfortable in asking questions about alcohol use when they believe the patient's health status is being influenced by drinking. ³³

Evidence for the effectiveness of a brief session with a physician in reducing patients' alcohol use and alcohol‐related morbidity is well documented. ³⁴ The most recent meta‐analysis in this area supports the efficacy of brief intervention (i.e., a specific intervention in one session, lasting about 10 minutes, concerning alcohol consumption, health risks, strategies to decrease alcohol intake, and brief reinforcing advice at follow‐up visits) for heavy drinking. ³⁵ Although the effects were moderate, with only an 11% difference in success rates between the brief intervention and control groups, the overall impact on hypertensive patients in the general population can be significant.

Maheswaran et al. ³⁶ evaluated the effectiveness of physician advice to reduce alcohol consumption in hypertensive patients. Brief advice and no‐advice control patients were followed for 18 months. In the advice group, alcohol consumption fell by 50% and was accompanied by an approximately 20% reduction in GGT. Control group patients showed no reduction in either drinking or GGT. Diastolic BP decreased significantly (by an average of 5.2 mm Hg) in the advice group compared with the control group.

CLINICAL IMPLICATIONS

This review clearly indicates 3 major facts: 1) heavy alcohol consumption and hypertension are strongly associated and the link between the two is most likely a causal one; 2) reductions in alcohol consumption can result in decreases in BP as well as improved compliance with medications and physician lifestyle recommendations; and 3) physicians can help to reduce heavy drinking in hypertensive patients. The obvious conclusion is that the routine evaluation of alcohol consumption (at least yearly) of hypertensive patients is warranted. ³⁷ Screening of treatment‐resistant hypertensive patients would seem to be especially important. In fact, JNC 7 lists excessive drinking as one of the six major causes of treatment‐resistant hypertension. ²

One of the briefest and most practical methods of evaluating hypertensive patients for alcohol abuse is the Alcohol Use Disorders Identification Test‐C (AUDIT‐C), a three‐question test adapted from the original AUDIT developed by the World Health Organization specifically for use in primary health care. ³⁸ The AUDIT is a well validated screening tool that has better sensitivity and specificity than the CAGE questions and shows more consistent results with the elderly, women, and differing cultural groups. ³⁹

The shortened version, the AUDIT‐C, is 99.7% as sensitive as the full 10‐question AUDIT, with a sensitivity of 86% and a specificity of 72%. ³⁸ , ⁴⁰ These questions (Table) are easy to score and can be embedded in a health questionnaire or asked directly by a nurse or physician.

Table.

AUDIT‐C Screening Questions

Questions	Score*
1. How often did you have a drink in the past year?	——
Never (0)
Monthly or less (1)
2 to 4 times a month (2)
2 to 3 times a week (3)
4 or more times a week (4)
2. How many drinks did you have on a typical day when you were drinking in the past year?	——
1 to 2 drinks (0)
3 to 4 drinks (1)
5 to 6 drinks (2)
7 to 9 drinks (3)
10 or more drinks (4)
3. How often did you have 6 or more drinks on one occasion in the past year?	——
Never (0)
Less than monthly (1)
Monthly (2)
Weekly (3)
Daily or almost daily (4)
	Total ——
AUDIT‐C=the Alcohol Use Disorders Identification Test; *a total score of ≥4 or a score of ≥1 on Question 3 is a positive screen and requires further evaluation and/or brief intervention (scores are indicated in parentheses after each response option). Reprinted with permission from Arch Intern Med. 1998;158:1789–1975. 38

Once screened, the most effective strategy for physician advice for heavy drinkers is a brief intervention—a 10‐minute conversation with the patient focusing specifically on the association between unhealthy drinking and BP. Other issues for discussion would include the negative impact of alcohol on the effectiveness of antihypertensive medications as well as on patient adherence to recommended lifestyle changes (e.g., diet, weight loss, exercise, and salt restriction). By emphasizing the alcohol–BP connection, the physician avoids confrontational disagreements about whether the patient has an “alcohol problem” or not.

During the brief intervention, the physician should give advice on lower limits or abstinence and provide strategies to reduce alcohol consumption (e.g., drinking nonalcoholic beer as a substitute). During follow‐up BP checks, drinking goals should be reviewed and progress reinforced. If both drinking and BP are reduced, the physician should make special mention of this connection. If the patient continues to drink heavily, it may be time to consider a referral for alcohol counseling.

Alcohol biomarkers can also be used to screen those hypertensive patients whose self‐reports are suspect. In an investigation of hypertensive patients in eight primary care clinics, Fleming and Mundt ⁴¹ found CDT to be especially useful in screening these patients for heavy drinking, with the test showing a 61% sensitivity and an 85% specificity. Alcohol biomarkers are also useful to monitor a patient's progress and provide objective feedback on reductions in drinking. ⁴² , ⁴³ A 30% decrease from baseline in either GGT or CDT is indicative of a significant reduction in alcohol consumption or abstinence. ⁴⁴ In the Malmo Prevention Project, ⁴¹ , ⁴⁵ , ⁴⁶ GGT was successfully used to monitor and provide feedback to patients, resulting in significant reductions in heavy drinking as well as reductions in hospitalizations and mortality over a period of 6 years.

CONCLUSIONS

Of the more than 60 million hypertensive patients in the United States, approximately 9.75 million drink at levels that could negatively impact their BP. ¹ , ⁴¹ Brief physician intervention could reduce alcohol consumption considerably in these patients. Based on the studies reviewed here, reductions in drinking could lead to at least a 2 mm Hg reduction in diastolic BP. The overall result in the general population would be a 17% decrease in the prevalence of hypertension, a 15% reduction in stroke, and a 6% reduction in the risk of coronary heart disease. ⁴⁷ Routine screening and brief intervention by physicians can significantly improve BP control and overall quality of care in hypertensive patients.