Effects of Alcohol Withdrawal in Hypertension: History
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Contributor:
Antonio Vacca
,
Luca Bulfone
,
Sebastiano Cicco
,
Gabriele Brosolo
,
Andrea Da Porto
,
Giorgio Soardo
,
Cristiana Catena
,
Leonardo A. Sechi

Alcoholic beverages are common components of diets worldwide and understanding their effects on humans’ health is crucial. Because hypertension is the leading risk factor for cardiovascular diseases and all-cause mortality. Two different clinical conditions can result from the interruption of alcohol consumption. In heavy alcohol drinkers, abrupt interruption of alcohol intake might result in an alcohol withdrawal syndrome (AWS), with a critical condition that might require hospitalization. Alternatively, chronic reduction/interruption of alcohol intake could be part of the lifestyle changes that are recommended for the achievement of better blood pressure control in hypertensive patients.

  • alcohol withdrawal
  • blood pressure
  • cardiovascular risk factors
  • diastolic dysfunction

1. Alcohol Withdrawal Syndrome and Hypertension

Abrupt interruption of alcohol intake in heavy drinkers may cause the onset of symptoms that characterize the AWS [1]. Tremors, sweating, agitation, nausea, vomiting, tachycardia, and hypertension begin in alcohol abusers 6 to 24 h after the last alcohol intake [1]. Only a few patients, however, evolve to the psychotic manifestations and cardiovascular collapse that are the features of the delirium tremens (DT).
Classical studies conducted on heavy alcohol consumers admitted for detoxification, but without DT, evaluated patients for hypertension [2]. Within 72 h of admission, blood pressure ≥160/95 mm Hg was found in 33% of patients, 71% of whom had transitory elevation, whereas 29% required drug treatment. Alcohol dependents with transitory hypertension were older, drank greater amounts of alcohol, and had higher blood pressure response to the cold pressor test that was associated with higher circulating catecholamines levels compared to normotensive alcohol dependents [2]. These observations clearly point to an activated sympathetic system as a major determinant of hypertensive response in AWS.
Ceccanti et al. investigated blood pressure changes in chronic alcohol dependents on early alcohol withdrawal that were followed for 18 days [3]. At baseline, hypertension was found in 55% of patients and in 21% at the end of follow-up, suggesting the transient nature of blood pressure increase was caused by alcohol withdrawal. Persistence of hypertension could be explained either by longer-lasting alcohol effects or alcohol-independent hypertension. Other studies examined the effects of alcohol withdrawal on endothelial function in heavy alcohol consumers who were compared with alcohol dependents that did not modify their drinking habits and teetotallers [4]. Next to in vivo analysis, human endothelial cells were exposed to ethanol in vitro for 2 weeks, assessing the same variables that were measured in patients after withdrawal of alcohol exposure. Endothelin-1, nitric oxide, plasminogen activator inhibitor-1 (PAI-1), and von Willebrand factor were measured in plasma and supernatants of cultured cells as markers of endothelial function. Malondialdehyde and intracellular glutathione were evaluated as markers of oxidative stress, a key mechanism causing endothelial dysfunction. Alcohol exposure increased the levels of endothelin-1, nitric oxide, and PAI-1, and decreased those of the von Willebrand factor, both in vivo and in vitro. These changes were dose-dependent and were reversed after withdrawal. It was concluded that heavy alcohol intake affects endothelial function, with an effect that is mediated by an activated oxidative stress and is rapidly reversed after withdrawal.
In another study carried out in 14 hypertensive heavy alcohol consumers with referred alcohol intake of more than 200 g/day, who were followed for 30 days, cessation of alcohol intake caused a rapid and significant fall in systolic and diastolic blood pressure when compared to eight hypertensive heavy drinkers who refused to reduce alcohol consumption [5]. By the third day after alcohol withdrawal, blood pressure had significantly decreased, and normalization of values was obtained in most patients by the end of the study. Cessation of alcohol intake significantly decreased plasma aldosterone and cortisol levels, whereas there were no effects on active renin and 24 h fractionated urinary catecholamines values. At baseline, hypertensive heavy drinkers had significantly higher levels of plasma endothelin and PAI-1 than teetotallers. During the study, both endothelin and PAI-1 levels progressively decreased in hypertensive heavy drinkers who stopped alcohol intake but remained elevated in patients who maintained alcohol consumption. This study confirmed that hypertension is rapidly reversible in most heavy alcohol consumers, after alcohol withdrawal, and suggested, once again, an important contribution of endothelial factors to blood pressure increase in these patients. These findings were further confirmed in moderate-to-heavy drinkers in whom blood pressure fell significantly within a few weeks after alcohol withdrawal [3][6][7][8][9].

2. Treatment of Hypertension in Alcohol Withdrawal Syndrome

Complete alcohol abstinence must be recommended to all hypertensive alcohol dependents, as transient hypertension ensuing after alcohol withdrawal was found to be harmless in all our subjects [3]. Therefore, abstinence leads to a complete recovery from hypertension, in most cases. Hypertension is typically self-limited in the AWS, and drug treatments should be applied just to prevent possible urgency- or emergency-related complications [10]. In patients for whom there is concern for hypertensive urgency or emergency, full medical evaluation is indicated to identify any potential end-organ damage [10]. Otherwise, a general goal is to reduce pressure over a period of hours to days, with a target blood pressure of less than 160/100 mm Hg, with no lowering by more than 25–30% over the first 3 h [11].
Few data are available on hypertension management of patients with the AWS. Blood pressure might be difficult to control in patients with underlying treatment-resistant hypertension, and multiple medications could be needed in some cases. Drugs commonly used in the general wards are benzodiazepines and, in intensive care units (ICU), dexmedetomidine. Both drugs effectively reduce systolic and diastolic blood pressure [12], acting at the level of central nervous system and reducing the sympathetic discharge. In addition, as demonstrated in vitro, benzodiazepines induce vasodilatation by endothelium-dependent and independent mechanisms [13]. In a retrospective case series collected in ICU patients with AWS, dexmedetomidine was effective in reducing blood pressure, allowing reduction of benzodiazepine administration [14]. Other drugs that were employed in treatment of AWS were oral clonidine and captopril [10][15] or, when needed, parenteral drugs such as nitroglycerin, labetalol, urapidil, or sodium nitroprusside [11][15][16].

3. Reduction of Alcohol Intake and Blood Pressure

Evidence of a causal role of heavy alcohol intake in hypertension would receive strong support from evidence that the discontinuation of alcohol consumption lowers blood pressure. For this reason, many studies, including randomized clinical trials, examined the effect of reduction/withdrawal of alcohol intake in hypertension [9][10][11][12][13][14]. Because of important heterogeneity in participants’ characteristics, assessment of adherence to alcohol restriction, and follow-up duration, evidence of the possible benefits of alcohol withdrawal on blood pressure reduction, obtained in these studies, is rather weak. In a randomized controlled trial that enrolled 641 participants who consumed at least 10 drinks per week, the effects on blood pressure of an intervention program, based on cognitive-behavioral alcohol reduction, was examined and compared with a control group after 15 to 24 months of follow-up [17]. Subjects in the intervention group reported a significant decrease (−191 g per week) of alcohol consumption, but there was no difference in blood pressure decrease in comparison to controls. Similar results were reported by Kawano et al. who used 24 h blood pressure monitoring in a crossover-study, reporting a decrease in daytime systolic blood pressure by 3 ± 9 mm Hg with restriction of alcohol intake, but no significant change in 24 h blood pressure [18].
A meta-analysis of 36 randomized controlled trials reported an association between short-term reduction in alcohol consumption and blood pressure decrease [19]. In this metanalysis, the overall effect of alcohol reduction was a decrease of 3 mm Hg for systolic and 2 mm Hg for diastolic blood pressure. However, stratification of analysis by the amount of baseline alcohol intake showed no effect on blood pressure for participants who consumed up to two drinks per day. Conversely, blood pressure reduction was significant and progressively higher in participants who had baseline alcohol intake of three, four to five, and six or more drinks per day. In this study, a meta-regression model indicated a decrease of 0.91 mm Hg in systolic and 0.75 mm Hg in diastolic blood pressure per one drink per day. A Cochrane review was set by Acin et al. to examine the effects of interventions to reduce alcohol intake on blood pressure for at least 3 months [20]. Results of the analysis were primarily determined by the randomized controlled trial reported in reference [17]. Alcohol intake was significantly reduced by interventions in comparison to control subjects, but reduction did not result in differences in systolic and diastolic blood pressure changes when compared to controls. Furthermore, no differences were observed for overall or cardiovascular mortality and major cardiovascular events.
An alternative strategy for the reduction of alcoholic beverage intake could be the use of dealcoholized wine. In a small cross-over trial, Chiva-Blanch et al. examined the short-term (4 weeks) effects of dealcoholized wine on blood pressure, reporting a significant reduction of both systolic (−5.8 mm Hg) and diastolic (−2.3 mm Hg) blood pressure that was associated with an increase in plasma nitric oxide levels [21]. Another interesting approach aiming at reducing alcohol intake is a nurse-based behavioral approach. This approach was tested in 28 Japanese heavy drinkers in whom the nurse-based program led to a decrease in blood pressure, as assessed by 24 h monitoring, in comparison to 25 controls [22]. In this study, blood pressure targets (<135/85 mm Hg) were reached in 55.6% of subjects who reduced alcohol consumption in the intervention group, and only 16.7% in the control group.
Thus, some studies and cumulative analyses do support the hypothesis of a significant benefit for blood pressure from the reduction/withdrawal of alcoholic beverage consumption. These observations led most scientific societies to provide the current recommendations regarding alcohol consumption. Nonetheless, it should be kept in mind that this evidence comes principally from small-sized and relatively short-lasting studies, and therefore, possible long-term benefits of alcohol reduction in hypertensive patients are still debated. Further studies will be needed to provide a better understanding of the potential benefits of the reduction of alcohol intake in hypertension.

This entry is adapted from the peer-reviewed paper 10.3390/nu15040958

References

  1. Tiglao, S.M.; Meisenheimer, E.S.; Oh, R.C. Alcohol Withdrawal Syndrome: Outpatient Management. Am. Fam. Physician 2021, 104, 253–262.
  2. Clark, L.T.; Friedman, H.S. Hypertension Associated with Alcohol Withdrawal: Assessment of Mechanisms and Complications. Alcohol. Clin. Exp. Res. 1985, 9, 125–130.
  3. Ceccanti, M.; Sasso, G.F.; Nocente, R.; Balducci, G.; Prastaro, A.; Ticchi, C.; Bertazzoni, G.; Santini, P.; Attilia, M.L. Hypertension in early Alcohol Withdrawal in Chronic Alcoholics. Alcohol Alcohol. 2006, 41, 5–10.
  4. Soardo, G.; Donnini, D.; Varutti, R.; Moretti, M.; Milocco, C.; Basan, L.; Esposito, W.; Casaccio, D.; Stel, G.; Catena, C.; et al. Alcohol-Induced Endothelial Changes Are Associated With Oxidative Stress and Are Rapidly Reversed After Withdrawal. Alcohol. Clin. Exp. Res. 2005, 29, 1889–1898.
  5. Soardo, G.; Donnini, D.; Varutti, R.; Milocco, C.; Basan, L.; Esposito, W.; Casaccio, D.; Isola, M.; Soldano, F.; Sechi, L.A. Effects of Alcohol Withdrawal on Blood Pressure in Hypertensive Heavy Drinkers. J. Hypertens. 2006, 24, 1493–1498.
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  7. Malhotra, H.; Mathur, D.; Mehta, S.R.; Khandelwal, P.D. Pressor Effects of Alcohol in Normotensive and Hypertensive Subjects. Lancet 1985, 326, 584–586.
  8. Potter, J.F.; Beevers, D.G. Pressor Effect of Alcohol in Hypertension. Lancet 1984, 323, 119–122.
  9. Ueshima, H.; Mikawa, K.; Baba, S.; Sasaki, S.; Ozawa, H.; Tsushima, M.; Kawaguchi, A.; Omae, T.; Katayama, Y.; Kayamori, Y. Effect of Reduced Alcohol Consumption on Blood Pressure in Untreated Hypertensive Men. Hypertension 1993, 21, 248–252.
  10. Bojdani, E.; Chen, A.; Zhang, T.; Naqvi, N.; Tahera, D. Hypertensive Urgency and Emergency in Alcohol Withdrawal: A Literature Review. Prim. Care Companion CNS Disord. 2019, 21, 27338.
  11. Williams, B.; Mancia, G.; Spiering, W.; Agabiti Rosei, E.; Azizi, M.; Burnier, M.; Clement, D.L.; Coca, A.; de Simone, G.; Dominiczak, A.; et al. 2018 ESC/ESH Guidelines for the Management of Arterial Hypertension. Eur. Heart J. 2018, 39, 3021–3104.
  12. Mendelson, N.; Gontmacher, B.; Vodonos, A.; Novack, V.; Abu-AjAj, M.; Wolak, A.; Shalev, H.; Wolak, T. Benzodiazepine Consumption Is Associated with Lower Blood Pressure in Ambulatory Blood Pressure Monitoring (ABPM): Retrospective Analysis of 4938 ABPMs. Am. J. Hypertens. 2018, 31, 431–437.
  13. Colussi, G.L.; Di Fabio, A.; Catena, C.; Chiuch, A.; Sechi, L.A. Involvement of Endothelium-Dependent and -Independent Mechanisms in Midazolam-Induced Vasodilation. Hypertens. Res. 2011, 34, 929–934.
  14. Frazee, E.N.; Personett, H.A.; Leung, J.G.; Nelson, S.; Dierkhising, R.A.; Bauer, P.R. Influence of Dexmedetomidine Therapy on the Management of Severe Alcohol Withdrawal Syndrome in Critically Ill Patients. J. Crit. Care 2014, 29, 298–302.
  15. Ram, C.V.S. Current Concepts in the Diagnosis and Management of Hypertensive Urgencies and Emergencies. Keio J. Med. 1990, 39, 225–236.
  16. Varon, J. The Diagnosis and Treatment of Hypertensive Crises. Postgrad. Med. 2009, 121, 5–13.
  17. Cushman, W.C. Prevention and Treatment of Hypertension Study (PATHS): Effects of an Alcohol Treatment Program on Blood Pressure. Arch. Intern. Med. 1998, 158, 1197.
  18. Kawano, Y.; Abe, H.; Takishita, S.; Omae, T. Effects of Alcohol Restriction on 24-Hour Ambulatory Blood Pressure in Japanese Men with Hypertension. Am. J. Med. 1998, 105, 307–311.
  19. Roerecke, M.; Kaczorowski, J.; Tobe, S.W.; Gmel, G.; Hasan, O.S.M.; Rehm, J. The effect of a reduction in alcohol consumption on blood pressure: A systematic review and meta-analysis. Lancet Public Health 2017, 2, e108–e120.
  20. Acin, M.T.; Rueda, J.-R.; Saiz, L.C.; Parent Mathias, V.; Alzueta, N.; Solà, I.; Garjón, J.; Erviti, J. Alcohol Intake Reduction for Controlling Hypertension. Cochrane Database Syst. Rev. 2020, 9, CD010022.
  21. Chiva-Blanch, G.; Urpi-Sarda, M.; Ros, E.; Arranz, S.; Valderas-Martínez, P.; Casas, R.; Sacanella, E.; Llorach, R.; Lamuela-Raventos, R.M.; Andres-Lacueva, C.; et al. Dealcoholized Red Wine Decreases Systolic and Diastolic Blood Pressure and Increases Plasma Nitric Oxide: Short Communication. Circ. Res. 2012, 111, 1065–1068.
  22. Kabayama, M.; Akagi, Y.; Wada, N.; Higuchi, A.; Tamatani, M.; Tomita, J.; Nakata, Y.; Takiuchi, S.; Yamamoto, K.; Sugimoto, K.; et al. A Randomized Trial of Home Blood-Pressure Reduction by Alcohol Guidance During Outpatient Visits: OSAKE Study. Am. J. Hypertens. 2021, 34, 1108–1115.
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