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Hypertension

HTN: Alcohol (2015)

Citation:

Stewart SH, Latham PK, Miller PM, Randall P, Anton RF. Blood pressure reduction during treatment for alcohol dependence: results from the COMBINE study. Addiction, 2008; 103 (10): 1,622-1,628.

PubMed ID: 18821872
 
Study Design:
Randomized Controlled Trial
Class:
A - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:
  • To evaluate blood pressure (BP) changes occurring during a large national alcohol dependence treatment protocol
  • To evaluate how demographic variations might affect such changes
  • To explore the effect of pharmacotherapies for relapse prevention on blood pressure.
Inclusion Criteria:
  • Participating in the COMBINE Study (Combined Behavioral Intervention and/or Medical Management) for treatment for alcohol dependence
  • Details of study have been published previously.
Exclusion Criteria:
Not reported.
Description of Study Protocol:
  • Recruitment: Participants were recruited from the general population or clinical settings at 11 centers throughout the US. Details have been published previously.
  • Design: Randomized controlled trial
  • Blinding used: Implied with measurements.

Intervention

  • The COMBINE study was a large multi-center alcohol dependence treatment trial completed in 2004. It was a randomized placebo-controlled trial of pharmacotherapy (naltrexone, acamprosate, or both) and counseling strategies.
  • In the present work, methods appropriate for repeated measures data were used to assess the relationship of percent drinking days (PDD) to systolic and diastolic BP over a 16-week treatment period. Modification of these associations by demographic and other variables was assessed.

Statistical Analysis

  • BP measurements on each subject were analyzed using a random coefficients model to account for within subject correlation
  • A two-slope piece-wise regression was used to model the observed biphasic relationship between BP and time. The fit of maximum likelihood models with fixed effects, random intercept and random slopes and intercept were compared using likelihood ratio tests.
  • The main effect of PDD on time slopes for BP and the interaction of baseline demographic variables and medication assignment with PDD were assessed by adding these terms to the model and conducted stratified analyses in the presence of any statistically significant interaction (P<0.05)
  • When demographic interactions with PDD were found, adjustment for these factors was undertaken in order to estimate whether these factors might mediate the interaction
  • History of hypertension, use of anti-hypertensive agents and body mass index (BMI) were not included in the main analyses due to missing baseline data but were adjusted for secondarily
  • The BP readings were measured according to the site and examiners usual routine, thus site effects were controlled in all analyses to partially account for non-standardized measurement.
Data Collection Summary:

Timing of Measurements

Blood pressure measurements at baseline (pre-treatment) and at Weeks Four, Eight, 12 and 16 of treatment were analyzed, as was the drinking that occurred at baseline and between each blood pressure assessment, i.e., during Weeks Zero through Four, Five through Eight, Nine through 12 and 13 through 16.

Dependent Variables

Systolic and diastolic BP (measured according to the site and examiners usual routine).

Independent Variables

Alcohol consumption was described by percent drinking days (PDD), defined as the percentage of all days on which any amount of alcohol was consumed (estimated by self-report using timeline follow-back methodology).

Control Variables

  • Age
  • Gender
  • Ethnicity
  • Pharmacotherapy
  • Self-reported hypertension history
  • Reported use of antihypertensive agents at baseline
  • BMI.
Description of Actual Data Sample:
  • Initial N: 1,383 subjects (69% male, 31% female)
  • Attrition (final N): 1,383. Of a total of 6,915 potential blood pressure measurements as defined for this analysis, 1,421 (20.5%) were missing. Only 808 subjects had complete data.
  • Age: Mean age, 44 years
  • Ethnicity: 76% non-Hispanic white, 12% Hispanic, 8% African-American, 4% others
  • Other relevant demographics: Not reported
  • Anthropometrics: Not reported
  • Location: Multi-center at 11 centers throughout the United States.
Summary of Results:

Key Findings

  • There was an initial drop in systolic and diastolic BP between baseline and Week Four, followed by a gently up-sloping curve between Weeks Four and 16
  • BP reduction was significant only in persons who were above the median BP (132mmHg for systolic and 84mmHg for diastolic) at baseline. In this group, systolic BP decreased by an average of 12mmHg and diastolic BP decreased by an average of eight mmHg. BP reduction was significant during the first month of treatment.
  • This observed effect was similar regardless of age, sex, body-mass index, reported history of hypertension and use of anti-hypertensive medications
  • When this analysis was performed using subjects with complete data (i.e., no missing values), the results did not differ much from the whole sample
  • Adjustment for PDD accounted for most of the initial change in BP. Adding PDD to the systolic BP model resulted in a change in the initial time slope from -4.9 (95% CI, -5.8 to -4.1) to -1.5 (95% CI, -2.7 to -0.3). Adding PDD to the diastolic BP model resulted in a corresponding change from -3.5 (95% CI, -4.0 to -2.9) to -1.1 (95% CI, -1.9 to -0.4). PDD adjustment had little impact on the modest increase in BP observed after Week Four.
  • There was a significant interaction between age and PDD for systolic BP but not diastolic pressure and the same pattern was seen for gender. For ethnicity, the effect of PDD on both systolic and diastolic BP differed between African-American and non-Hispanic white subjects. Naltrexone or acamprosate treatment did not impact the relationship between PDD and BP.
  • An observed association between BP and PDD in Caucasians was not evident in African-Americans, largely due to their lower pre-treatment BP.

Predicted Average BP Reduction Associated with a 50% Decrease in PDD

Demographic Variable Systolic BP Reduction (mmHg) Diastolic BP Reduction (mmHg)
Age <44 2.6 (P<0.001)  
≥44 3.2 (P<0.001)  
Gender Female 3.1 (P<0.001)  
Male 3.1 (P<0.001)  
Ethnicity African-American 1.1 (P=0.515) 0.49 (P=0.657)
Non-African-American 3.2 (P<0.001) 2.3 (P<0.001)
Ethnicity with Adjustment for Baseline BP>Sample Average African-American 2.0 (P=0.212) 1.6 (P=0.128)
Non-African-American 2.4 (P<0.001) 1.9 (P<0.001)
Author Conclusion:
  • Reduction in alcohol consumption has a potent anti-hypertensive effect in alcoholics with higher blood pressure
  • For hypertensive, alcohol-dependent persons, treatment for alcoholism should be considered a major component of anti-hypertensive therapy.
Funding Source:
Government: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Reviewer Comments:
  • PDD was chosen to describe consumption, as the correlation of this measure with BP was slightly higher than other consumption measures at pre-treatment baseline
  • Strengths of this study: Use of a large trial database with repeated and detailed assessment of daily alcohol use over time, repeated blood pressure measurement and adequate representation of women and several ethnic groups
  • The main limitation of this study: Non-standardized measurement of BP; measurement error was inevitable since the COMBINE Study was not designed to assess BP as a treatment outcome
  • About 20% of observations were missing and these were assumed to be random. Since missing data may very well be related to alcohol consumption, this assumption could have resulted in an overestimation of the average reduction in BP over time.
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? ???
  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? ???
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) ???
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? ???
  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? ???
  4.1. Were follow-up methods described and the same for all groups? ???
  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%.) ???
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? ???
  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? ???
  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? ???
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
  6.6. Were extra or unplanned treatments described? ???
  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? ???
  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? N/A
  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? ???
  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