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Hypertension

HTN: Alcohol (2015)

Citation:

Soardo G, Donnini D, Varutti R, Milocco C, Basan L, Esposito W, Casaccio D, Isola M, Soldano F, Sechi LA. Effects of alcohol withdrawal on blood pressure in hypertensive heavy drinkers. J Hypertens. 2006; 24: 1,493-1,498. 

PubMed ID: 16877950
 
Study Design:
Non-Randomized Controlled Trial
Class:
C - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:
To evaluate the effects of alcohol withdrawal on blood pressure and plasma markers of endothelial activity in chronic heavy alcohol consumers with hypertension. 
Inclusion Criteria:
  • Untreated hypertensive heavy alcohol consumers with a referred alcohol intake of over 200g per day, lasting for a minimum of 10 years
  • Agreed to start a hospital withdrawal program
  • Fulfilled the diagnostic criteria for alcohol dependence, as defined by CAGE questionnaire.
Exclusion Criteria:
  • Age over 65 years
  • BMI under 20 or over 25
  • Smoking more than 10 cigarettes per day
  • Use of hypertensive drugs in the previous year
  • Blood pressure over 180/120mmHg
  • Established diagnosis of secondary hypertension; diabetes; coronary artery, cardiovascular or peripheral arterial disease, renal failure, liver cirrhosis, other significant diseases or drug treatments that could interfere with endothelial function.
Description of Study Protocol:
  • Recruitment: Consecutive patients over a nine-month period at outpatient liver clinic
  • Design: Non-randomized controlled trial
  • Blinding used: Implied with measurements
  • Intervention: Participation in a hospital alcohol withdrawal program.

Statistical Analysis

  • Shapiro-Wilk and Levene's test to assess for normality and homogeneity of variances of the distributions, respectively
  • For comparisons of variables normally distributed Student's T-test was used
  • For variables not normally distributed, the ANOVA or Kruskal-Wallis test, with Bonferroni correction (if required), were used
  • Pearson's or Spearman's correlation coefficients and forward stepwise regression analysis to assess blood pressure changes.
Data Collection Summary:

Timing of Measurements

Withdrawal Group
  • Daily body weight, 24-hour urine volume, heart and respiratory rate, sitting BP and lab parameters (24-hour urinary sodium and fractionated catecholamine excretion; plasma active renin, aldosterone, cortisol; biochemical indicators of liver damage and liver function; ethanol levels; plasma gamma-glutamyltranspeptidase and mean erythrocyte corpuscular volume) at baseline and 30 days
  • Liver biopsy on Day Three
  • Blood for plasma endothelin and plasminogen activator inhibitor 1 (PAI-1) on Days Three, Seven, 15 and 30.
Untreated and Normotensive Groups
Blood drawn on Days Zero, 15 and 30. 

Dependent Variables

  • Body weight
  • Sodium and fractionate catecholamine excretion measured through 24-hour urinary volume
  • Heart and respiratory rate
  • Blood pressure measured as mean value of three measurements at three-minute intervals after sitting for 10 minutes 
  • Plasma active renin, aldosterone, cortisol, liver damage, liver function, ethanol level, plasma gamma-glutamyltranspeptidse and mean erythrocyte corpuscular volume measured through blood draw.

Independent Variables

Alcohol withdrawal vs. continuing alcohol intake in heavy alcohol users vs. non-drinkers.

Control Variables

Hospital diet.
Description of Actual Data Sample:
  • Initial N: 14 withdrawal (12 males, two females); eight non-withdrawal (six males, two females); 11 normotensive (nine males, two females)
  • Attrition (final N): No attrition reported, as above
  • Age: 53±3 years, 57±3 years and 49±9 years, respectively
  • Ethnicity: Caucasian.

Anthropometrics
No differences in clinical and biochemical indicators of liver damage and function.

Location
Italy.

Summary of Results:

Key Findings

  • Liver function tests were within normal range at baseline and did not change significantly for both groups of drinkers
  • Cessation of alcohol intake progressively decreased average levels of both systolic and diastolic blood pressure, reaching normal levels after one week 
  • Normalization of blood pressure levels (less than 140/90mmHg) was obtained in 13 of 14 abstainers with an 18% decrease in mean blood pressure values (from 119±9mmHg to 98±8mmHg) 
  • The magnitude of blood pressure change was significantly and positively correlated with baseline blood pressure values (R=-0.60; P<0.02)
  • Plasma aldosterone and plasma cortisol were significantly decreased by alcohol abstinence (P<0.05 and P<0.02, respectively)
  • Plasma endothelin and PAI-1 were significantly greater in alcoholic individuals than teetotalers and the cessation of alcohol induced a rapid decrease in both levels
  • This decrease was significant after one week and reached stable values after two weeks of continued decrease
  • At Day 30, both endothelin and PAI-1 changes were related to systolic (R=0.55, P<0.001 and R=0.55, P<0.001, respectively), but not diastolic blood pressure changes
  • Only endothelin was independently correlated (P<0.01) with systolic pressure variation over the study.
Author Conclusion:
  • Hypertension is rapidly reversible in the majority of heavy drinkers after the withdrawal of alcohol consumption
  • In these patients, hypertension is associated with an increased release of endothelial factors that might contribute to the increase in blood pressure. 
Funding Source:
University/Hospital: Department of Internal Medicine, Liver Unit and Hypertension Unit, Department of Experimental and Clinical Pathology and Medicine and Institute of Statistics, Department of Medical and Morphological Research, University of Udine School of Medicine, Udine, Italy
Reviewer Comments:
  • Small numbers of subjects in groups
  • Authors note that a limitation of the study was the lack of inclusion of a group of normotensive heavy alcohol consumers.
Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
 
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? ???
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? Yes
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) Yes
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? N/A
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? Yes
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? N/A
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? Yes
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) Yes
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? Yes
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? N/A
  6.6. Were extra or unplanned treatments described? N/A
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? Yes
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? N/A
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? N/A
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes